50th Anniversary

Wilma F. Bergfeld, MD, one of only five women in her medical school class of 1964 and the third female in her dermatology residency program, had recently been appointed as a junior clinical dermatologist and head of dermatopathology at the Cleveland Clinic when she was told by a superior that she would not be promoted or invited to serve on any committee or decision-making group.

“I was told I should go home at night and take care of my husband and two children,” she recalled of that moment in the 1970s. The comment made her feel “outraged,” and it drove her, calmly and steadily, to work harder and to “challenge the system.”

Dr. Bergfeld not only was elected to the Cleveland Clinic’s board of governors and board of trustees and served as president of the Clinic’s staff in 1990, she also became the first woman president of the American Academy of Dermatology (1992) and led numerous other dermatologic organizations. Much earlier on, in 1973, to help fulfill her vision of “women helping women,” she had also founded the Women’s Dermatologic Society (WDS). Three years earlier, in 1970, 6.9% of the approximately 4,000 dermatologists in the United States were women, according to the American Medical Association.

Dr. Bergfeld’s career trajectory in leadership, education, and patient care paralleled a rise of women in dermatology. Today, when she goes to work as the long-time director of the Clinic’s dermatopathology fellowship and professor of dermatology and pathology at the Cleveland Clinic Educational Foundation, she sees a transformed staff and, more broadly, a national physician workforce in which women made up almost 50% of active dermatologists in 2017 and almost 60% of dermatology residents in 2018, according to data from the American Association of Medical Colleges.

It’s a different and better world, she and other women dermatologists said, but one in which women must continue to mentor other women and continue to challenge the system. Achieving work-life balance, fairer compensation, and a greater proportion of women in the higher ranks of academia are all on their work list.
 

Women’s impact on the specialty

Dr. Bergfeld and Molly Hinshaw, MD, the current president of the WDS, said they believe women are drawn to dermatology for its visual nature, the growth in diagnostic tests and therapies, and the opportunity to diagnose early and prevent progression of disease in patients of all ages. “It’s a small but mighty specialty,” said Dr. Hinshaw, associate professor of dermatology and section chief of dermatopathology at the University of Wisconsin–Madison.

It’s also a versatile specialty with a variety of subspecialties and niches to pursue – and women have been stepping in to fill unmet needs, Dr. Hinshaw said. “Women dermatologists are directing vulvar specialty clinics across the country, for example. There aren’t that many, but they’re filling an important niche. We have one at [our university] and it is packed.”

Women have also been drawn to the in-demand subspecialty of pediatric dermatology, she noted. They now make up more than two-thirds of all pediatric dermatologists, and many in practice have trained the old-fashioned way, completing two residencies. “That’s [involved] self-selection into an additional year of years training and a commitment to caring for special populations that, quite honestly, takes more time,” said Dr. Hinshaw, who, as part of her dermatology practice, runs a nail clinic at UW Health in Madison.

Amy S. Paller, MD, who chairs the department of dermatology at Northwestern University, Chicago, where she is professor of dermatology and pediatrics and directs the Skin Biology & Diseases Resource-Based Center, is one of these women. She took a long and determined journey into the subspecialty, encountering bias and discouragement while actively seeking out mentors who helped her advance.

Courtesy of Northwestern Memorial HealthCare

While in medical school at Stanford (Calif.) University in the late 1970s in a class “very progressively” made up of about one-third women, Dr. Paller met Alvin Jacobs, MD, who, in 1975, had founded the Society for Pediatric Dermatology. “There wasn’t much pediatric dermatology in the world at the time, and it was Al who helped [me realize] that it combined my love of genetic research with my [desire] to work with children,” she recalled.

Per Dr. Jacob’s advice, she went to Northwestern to train in both pediatrics and dermatology under Nancy Esterly, MD, who “is considered by many to be the mother of pediatric dermatology.” And knowing that she wanted to do research, Dr. Paller also worked with Ruth Freinkel, MD, who “was the strongest bench researcher” at Northwestern. (Dr. Freinkel had been one of the first female dermatology residents at Harvard and was the first full-time faculty member in dermatology at Northwestern).

After completing postdoctoral research at the University of North Carolina at Chapel Hill, Dr. Paller returned to Chicago and assumed Dr. Esterly’s position as chief of dermatology at the Children’s National Hospital of Chicago. It was there that “someone in a leadership position questioned me about how I could possibly be a scientist, a strong clinician, and a good mother to my three children – and suggested that I drop research,” Dr. Paller recalled.

“I think this person was trying to be helpful to me, but I was shocked,” she said. Just as Dr. Bergfeld had done, Dr. Paller channeled her frustration into new pursuits.

“It made me go home and think, how could I strengthen myself? What else could I do?” she said. “Soon after, with a highly supportive husband, I did a ‘pseudosabbatical,’ basically spending every ounce of spare time I had working with one of the premier female scientists in the country, Elaine Fuchs, and learning molecular biology” in her lab at the University of Chicago.

“I think we’ve all had discrimination along the way. Sometimes there’s implicit bias and sometimes there’s overt bias,” said Dr. Paller, who in 2004 led the society which her mentor Dr. Jacobs had founded several decades earlier. “I just jumped right in, and that’s enabled me to find good role models.”

Across dermatology broadly, the often holistic nature of the specialty – of the ability to peer into the body and its internal health – is another quality that women have been drawn to and advanced, Dr. Hinshaw said. “One of the reasons why I chose dermatology is because it’s a window to total patient health. Patients often see their dermatologists as physicians who help them identify next steps in their health care, who can help them address issues related to their overall health and well-being, including their mental health.”

In a WDS membership survey conducted in 2018, most respondents reported that they frequently or occasionally detect and diagnose systemic/internal diseases and conditions in their female patients, and that they consult and collaborate with different kinds of physicians (Int J Womens Dermatol. 2018 Nov 15;4[4]:189-92).

And in a March 2019 “Dialogues in Dermatology” podcast episode on the history and advancement of women in dermatology produced by the American Academy of Dermatology, Pearl Grimes, MD, a clinical professor of dermatology of the University of California, Los Angeles, and then-president of the WDS, described why “total women’s health” had become an additional focus for the society.

“We’re already gatekeepers” in many respects, Dr. Grimes said. “In addition to my addressing specific skin issues, my patients query me on hormone issues, on nutrition, on stress-related issues….and on [what other physicians they should see].”

Disparities in academia

Dermatology departments in academic medicine have burgeoned in size in the past 50 years, and women are well represented overall. In 2018, women comprised 51.2% of dermatology department faculty – up from 10.8% in 1970 – a current proportion that ranks fifth among specialties for the proportion of female faculty, according to a cross-sectional study of faculty diversity trends using data from the AAMC faculty roster (JAMA Dermatol. 2020 Jan 8;156[3]:280-7).

The AAMC data show the share of women dermatology faculty declining at each subsequent rank, however – a finding that suggests that women are not promoted as quickly or to the same levels of leadership as men, the report’s authors noted. (Dermatology isn’t alone: The AAMC issued a call to action on gender equity in medicine this year, citing this inverse association.)

Another recently published study of gender trends in academic dermatology – this one looking at a smaller sample of data from 15 institutions – similarly found that women dermatologists made up a majority of faculty (53.6%) and were well represented as assistant professors (60.7%) but underrepresented as full professors (17%).

This study differed from the larger AAMC study, however, in that it controlled for “achievement indicators” – career duration, publications per year, and National Institutes of Health research funding – and found that gender alone was not associated with higher rank. Instead, promotions were correlated most significantly with NIH research funding and also with career duration and publications per year.

“If research achievement is to be used as a benchmark for academic promotion, increased efforts are needed to support the research activities of women,” the authors wrote, adding that recognition should be given to other factors as well.

Dr. Paller and Dr. Hinshaw both described the situation as complex and multifaceted. Some research on promotion in academia in general – but not all – has suggested that women do need to publish more than men in order to be promoted. But “the promotion process also has within it the ability to use judgment [about] the impact and merits of work,” said Dr. Hinshaw. “Not all publications [and levels of authorship] may be considered equal, for instance.”

Dr. Hinshaw said she is also concerned by data showing that women still perform the majority of household duties, “even in households in which both partners work outside the home equivalently.” As long as this is the case, women may be “inherently disadvantaged” in their ability to have adequate research time and to advance.

From where she sits, Dr. Paller sees several factors at play: “The pipeline, achievement during the pipeline, and decision-making about advancement” on the part of women themselves. Having served on search committees for top leadership in specialties in which women are well represented, she said, “I’ve seen fewer women who’ve come forward and been interested in rising into a chair or a dean position.”

And “having talked to so many women,” Dr. Paller added, “I think there’s a phenomenon where it’s harder for women to accept positions [that require] a significant change.”

Women “are nurturers, which makes them extremely good [leaders] and chairs, but it also makes it harder to make life changes that affect the people they love,” she said, noting that becoming a department chair or a dean often involves moving. “I also think that women in general are happier and committed to what they’re [currently] doing.”

Dr. Paller is optimistic that, with the support of department chairs and continued attention to role modeling and mentoring, the portrait of women in academic dermatology will continue to improve. Currently, 34 chairs of dermatology departments are female, she noted. “That number was 11 less 15 years ago.”

In the meantime, researchers are increasingly documenting trends in women’s editorships of journals as well as leadership and speaking opportunities at professional conferences.

The authors of one study published this year, for instance, reviewed the editorial boards of dermatology journals and found that women occupied 18% of editor in chief roles, 36% of deputy editor positions, and 22% of overall editorial board roles (Int J Womens Dermatol. 2019 Sep 12;6[1]:20-4). Other research shows women comprising 43% of all authorships across 23 dermatologic journals from 2008 to May 2017, 50.2% of first authorships, and 33.1% of last authorships (BMJ Open. 2018 Apr 13;8[4]:e020089).

Both in academic medicine and in practice, a gender pay gap still affects women physicians across the board. Medscape’s 2020 dermatologist compensation report shows male dermatologists earning about 12% more than their female peers (average, $435,000 vs. $387,000, respectively), while the average number of hours per week spent seeing patients is similar (36.2 vs. 35.6 hours, respectively).

And in its 2020 statement on gender equity, the AAMC said that women in academic medicine are offered less in starting salary, negotiated pay, and other forms of compensation than men “despite equal effort, rank, training, and experience.”

It’s complicated to tease apart all the factors that may be involved – but important to keep challenging the system, said Dr. Bergfeld, who was a long-time board adviser for Dermatology News. “I was underpaid,” she noted, and “this was only rectified in the last 10 years.”

 

Work-life balance

In the AAD podcast on women in dermatology, Dr. Grimes said that achieving a healthy and balanced work life remains one of the greatest challenges for women dermatologists – and it may be even greater than in the past given the growing numbers of group practices. “When women enter the realm of group practice, they have less flexibility in controlling their time and their own schedules.”

If Anna Hare, MD, is any indication, younger dermatologists may buck this trend. The daughter of Dr. Rich in Portland, Dr. Hare joined her mother’s dermatology practice and research center knowing that she’d have “the respect and flexibility for deciding how I want to practice.”

Younger dermatologists, she said, place “more of an emphasis on work-life balance and quality of life.”

Fortunately, said Dr. Bergfeld, women have advanced enough in the ranks of dermatology that, in networking, in mentorship, and in workplace settings, attention can be paid more fully to discussions about work-life management – “how to manage your life when you’re working with family and kids and parents.”

In the 1970s, at the Cleveland Clinic, “there were only five women on staff and we were fighting for [basic] rights,” she said. “We wanted equality – we were [perceived as] little worker bees….We needed to climb as the men did to positions of leadership and address the problems of women.”

In pursuing their goals and making further progress, women dermatologists today should be “steady and calm,” she advised. Formally acquiring leadership skills and communication skills is a timeless need. And when there are biases or conflicts, “you cannot have righteous indignation, you cannot have revenge. You have to calm yourself and move forward.”

Wilma F. Bergfeld, MD, one of only five women in her medical school class of 1964 and the third female in her dermatology residency program, had recently been appointed as a junior clinical dermatologist and head of dermatopathology at the Cleveland Clinic when she was told by a superior that she would not be promoted or invited to serve on any committee or decision-making group.

“I was told I should go home at night and take care of my husband and two children,” she recalled of that moment in the 1970s. The comment made her feel “outraged,” and it drove her, calmly and steadily, to work harder and to “challenge the system.”

Dr. Bergfeld not only was elected to the Cleveland Clinic’s board of governors and board of trustees and served as president of the Clinic’s staff in 1990, she also became the first woman president of the American Academy of Dermatology (1992) and led numerous other dermatologic organizations. Much earlier on, in 1973, to help fulfill her vision of “women helping women,” she had also founded the Women’s Dermatologic Society (WDS). Three years earlier, in 1970, 6.9% of the approximately 4,000 dermatologists in the United States were women, according to the American Medical Association.

Dr. Bergfeld’s career trajectory in leadership, education, and patient care paralleled a rise of women in dermatology. Today, when she goes to work as the long-time director of the Clinic’s dermatopathology fellowship and professor of dermatology and pathology at the Cleveland Clinic Educational Foundation, she sees a transformed staff and, more broadly, a national physician workforce in which women made up almost 50% of active dermatologists in 2017 and almost 60% of dermatology residents in 2018, according to data from the American Association of Medical Colleges.

It’s a different and better world, she and other women dermatologists said, but one in which women must continue to mentor other women and continue to challenge the system. Achieving work-life balance, fairer compensation, and a greater proportion of women in the higher ranks of academia are all on their work list.
 

Women’s impact on the specialty

Dr. Bergfeld and Molly Hinshaw, MD, the current president of the WDS, said they believe women are drawn to dermatology for its visual nature, the growth in diagnostic tests and therapies, and the opportunity to diagnose early and prevent progression of disease in patients of all ages. “It’s a small but mighty specialty,” said Dr. Hinshaw, associate professor of dermatology and section chief of dermatopathology at the University of Wisconsin–Madison.

It’s also a versatile specialty with a variety of subspecialties and niches to pursue – and women have been stepping in to fill unmet needs, Dr. Hinshaw said. “Women dermatologists are directing vulvar specialty clinics across the country, for example. There aren’t that many, but they’re filling an important niche. We have one at [our university] and it is packed.”

Women have also been drawn to the in-demand subspecialty of pediatric dermatology, she noted. They now make up more than two-thirds of all pediatric dermatologists, and many in practice have trained the old-fashioned way, completing two residencies. “That’s [involved] self-selection into an additional year of years training and a commitment to caring for special populations that, quite honestly, takes more time,” said Dr. Hinshaw, who, as part of her dermatology practice, runs a nail clinic at UW Health in Madison.

Amy S. Paller, MD, who chairs the department of dermatology at Northwestern University, Chicago, where she is professor of dermatology and pediatrics and directs the Skin Biology & Diseases Resource-Based Center, is one of these women. She took a long and determined journey into the subspecialty, encountering bias and discouragement while actively seeking out mentors who helped her advance.

Courtesy of Northwestern Memorial HealthCare

While in medical school at Stanford (Calif.) University in the late 1970s in a class “very progressively” made up of about one-third women, Dr. Paller met Alvin Jacobs, MD, who, in 1975, had founded the Society for Pediatric Dermatology. “There wasn’t much pediatric dermatology in the world at the time, and it was Al who helped [me realize] that it combined my love of genetic research with my [desire] to work with children,” she recalled.

Per Dr. Jacob’s advice, she went to Northwestern to train in both pediatrics and dermatology under Nancy Esterly, MD, who “is considered by many to be the mother of pediatric dermatology.” And knowing that she wanted to do research, Dr. Paller also worked with Ruth Freinkel, MD, who “was the strongest bench researcher” at Northwestern. (Dr. Freinkel had been one of the first female dermatology residents at Harvard and was the first full-time faculty member in dermatology at Northwestern).

After completing postdoctoral research at the University of North Carolina at Chapel Hill, Dr. Paller returned to Chicago and assumed Dr. Esterly’s position as chief of dermatology at the Children’s National Hospital of Chicago. It was there that “someone in a leadership position questioned me about how I could possibly be a scientist, a strong clinician, and a good mother to my three children – and suggested that I drop research,” Dr. Paller recalled.

“I think this person was trying to be helpful to me, but I was shocked,” she said. Just as Dr. Bergfeld had done, Dr. Paller channeled her frustration into new pursuits.

“It made me go home and think, how could I strengthen myself? What else could I do?” she said. “Soon after, with a highly supportive husband, I did a ‘pseudosabbatical,’ basically spending every ounce of spare time I had working with one of the premier female scientists in the country, Elaine Fuchs, and learning molecular biology” in her lab at the University of Chicago.

“I think we’ve all had discrimination along the way. Sometimes there’s implicit bias and sometimes there’s overt bias,” said Dr. Paller, who in 2004 led the society which her mentor Dr. Jacobs had founded several decades earlier. “I just jumped right in, and that’s enabled me to find good role models.”

Across dermatology broadly, the often holistic nature of the specialty – of the ability to peer into the body and its internal health – is another quality that women have been drawn to and advanced, Dr. Hinshaw said. “One of the reasons why I chose dermatology is because it’s a window to total patient health. Patients often see their dermatologists as physicians who help them identify next steps in their health care, who can help them address issues related to their overall health and well-being, including their mental health.”

In a WDS membership survey conducted in 2018, most respondents reported that they frequently or occasionally detect and diagnose systemic/internal diseases and conditions in their female patients, and that they consult and collaborate with different kinds of physicians (Int J Womens Dermatol. 2018 Nov 15;4[4]:189-92).

And in a March 2019 “Dialogues in Dermatology” podcast episode on the history and advancement of women in dermatology produced by the American Academy of Dermatology, Pearl Grimes, MD, a clinical professor of dermatology of the University of California, Los Angeles, and then-president of the WDS, described why “total women’s health” had become an additional focus for the society.

“We’re already gatekeepers” in many respects, Dr. Grimes said. “In addition to my addressing specific skin issues, my patients query me on hormone issues, on nutrition, on stress-related issues….and on [what other physicians they should see].”

Disparities in academia

Dermatology departments in academic medicine have burgeoned in size in the past 50 years, and women are well represented overall. In 2018, women comprised 51.2% of dermatology department faculty – up from 10.8% in 1970 – a current proportion that ranks fifth among specialties for the proportion of female faculty, according to a cross-sectional study of faculty diversity trends using data from the AAMC faculty roster (JAMA Dermatol. 2020 Jan 8;156[3]:280-7).

The AAMC data show the share of women dermatology faculty declining at each subsequent rank, however – a finding that suggests that women are not promoted as quickly or to the same levels of leadership as men, the report’s authors noted. (Dermatology isn’t alone: The AAMC issued a call to action on gender equity in medicine this year, citing this inverse association.)

Another recently published study of gender trends in academic dermatology – this one looking at a smaller sample of data from 15 institutions – similarly found that women dermatologists made up a majority of faculty (53.6%) and were well represented as assistant professors (60.7%) but underrepresented as full professors (17%).

This study differed from the larger AAMC study, however, in that it controlled for “achievement indicators” – career duration, publications per year, and National Institutes of Health research funding – and found that gender alone was not associated with higher rank. Instead, promotions were correlated most significantly with NIH research funding and also with career duration and publications per year.

“If research achievement is to be used as a benchmark for academic promotion, increased efforts are needed to support the research activities of women,” the authors wrote, adding that recognition should be given to other factors as well.

Dr. Paller and Dr. Hinshaw both described the situation as complex and multifaceted. Some research on promotion in academia in general – but not all – has suggested that women do need to publish more than men in order to be promoted. But “the promotion process also has within it the ability to use judgment [about] the impact and merits of work,” said Dr. Hinshaw. “Not all publications [and levels of authorship] may be considered equal, for instance.”

Dr. Hinshaw said she is also concerned by data showing that women still perform the majority of household duties, “even in households in which both partners work outside the home equivalently.” As long as this is the case, women may be “inherently disadvantaged” in their ability to have adequate research time and to advance.

From where she sits, Dr. Paller sees several factors at play: “The pipeline, achievement during the pipeline, and decision-making about advancement” on the part of women themselves. Having served on search committees for top leadership in specialties in which women are well represented, she said, “I’ve seen fewer women who’ve come forward and been interested in rising into a chair or a dean position.”

And “having talked to so many women,” Dr. Paller added, “I think there’s a phenomenon where it’s harder for women to accept positions [that require] a significant change.”

Women “are nurturers, which makes them extremely good [leaders] and chairs, but it also makes it harder to make life changes that affect the people they love,” she said, noting that becoming a department chair or a dean often involves moving. “I also think that women in general are happier and committed to what they’re [currently] doing.”

Dr. Paller is optimistic that, with the support of department chairs and continued attention to role modeling and mentoring, the portrait of women in academic dermatology will continue to improve. Currently, 34 chairs of dermatology departments are female, she noted. “That number was 11 less 15 years ago.”

In the meantime, researchers are increasingly documenting trends in women’s editorships of journals as well as leadership and speaking opportunities at professional conferences.

The authors of one study published this year, for instance, reviewed the editorial boards of dermatology journals and found that women occupied 18% of editor in chief roles, 36% of deputy editor positions, and 22% of overall editorial board roles (Int J Womens Dermatol. 2019 Sep 12;6[1]:20-4). Other research shows women comprising 43% of all authorships across 23 dermatologic journals from 2008 to May 2017, 50.2% of first authorships, and 33.1% of last authorships (BMJ Open. 2018 Apr 13;8[4]:e020089).

Both in academic medicine and in practice, a gender pay gap still affects women physicians across the board. Medscape’s 2020 dermatologist compensation report shows male dermatologists earning about 12% more than their female peers (average, $435,000 vs. $387,000, respectively), while the average number of hours per week spent seeing patients is similar (36.2 vs. 35.6 hours, respectively).

And in its 2020 statement on gender equity, the AAMC said that women in academic medicine are offered less in starting salary, negotiated pay, and other forms of compensation than men “despite equal effort, rank, training, and experience.”

It’s complicated to tease apart all the factors that may be involved – but important to keep challenging the system, said Dr. Bergfeld, who was a long-time board adviser for Dermatology News. “I was underpaid,” she noted, and “this was only rectified in the last 10 years.”

 

Work-life balance

In the AAD podcast on women in dermatology, Dr. Grimes said that achieving a healthy and balanced work life remains one of the greatest challenges for women dermatologists – and it may be even greater than in the past given the growing numbers of group practices. “When women enter the realm of group practice, they have less flexibility in controlling their time and their own schedules.”

If Anna Hare, MD, is any indication, younger dermatologists may buck this trend. The daughter of Dr. Rich in Portland, Dr. Hare joined her mother’s dermatology practice and research center knowing that she’d have “the respect and flexibility for deciding how I want to practice.”

Younger dermatologists, she said, place “more of an emphasis on work-life balance and quality of life.”

Fortunately, said Dr. Bergfeld, women have advanced enough in the ranks of dermatology that, in networking, in mentorship, and in workplace settings, attention can be paid more fully to discussions about work-life management – “how to manage your life when you’re working with family and kids and parents.”

In the 1970s, at the Cleveland Clinic, “there were only five women on staff and we were fighting for [basic] rights,” she said. “We wanted equality – we were [perceived as] little worker bees….We needed to climb as the men did to positions of leadership and address the problems of women.”

In pursuing their goals and making further progress, women dermatologists today should be “steady and calm,” she advised. Formally acquiring leadership skills and communication skills is a timeless need. And when there are biases or conflicts, “you cannot have righteous indignation, you cannot have revenge. You have to calm yourself and move forward.”

Wilma F. Bergfeld, MD, one of only five women in her medical school class of 1964 and the third female in her dermatology residency program, had recently been appointed as a junior clinical dermatologist and head of dermatopathology at the Cleveland Clinic when she was told by a superior that she would not be promoted or invited to serve on any committee or decision-making group.

“I was told I should go home at night and take care of my husband and two children,” she recalled of that moment in the 1970s. The comment made her feel “outraged,” and it drove her, calmly and steadily, to work harder and to “challenge the system.”

Dr. Bergfeld not only was elected to the Cleveland Clinic’s board of governors and board of trustees and served as president of the Clinic’s staff in 1990, she also became the first woman president of the American Academy of Dermatology (1992) and led numerous other dermatologic organizations. Much earlier on, in 1973, to help fulfill her vision of “women helping women,” she had also founded the Women’s Dermatologic Society (WDS). Three years earlier, in 1970, 6.9% of the approximately 4,000 dermatologists in the United States were women, according to the American Medical Association.

Dr. Bergfeld’s career trajectory in leadership, education, and patient care paralleled a rise of women in dermatology. Today, when she goes to work as the long-time director of the Clinic’s dermatopathology fellowship and professor of dermatology and pathology at the Cleveland Clinic Educational Foundation, she sees a transformed staff and, more broadly, a national physician workforce in which women made up almost 50% of active dermatologists in 2017 and almost 60% of dermatology residents in 2018, according to data from the American Association of Medical Colleges.

It’s a different and better world, she and other women dermatologists said, but one in which women must continue to mentor other women and continue to challenge the system. Achieving work-life balance, fairer compensation, and a greater proportion of women in the higher ranks of academia are all on their work list.
 

Women’s impact on the specialty

Dr. Bergfeld and Molly Hinshaw, MD, the current president of the WDS, said they believe women are drawn to dermatology for its visual nature, the growth in diagnostic tests and therapies, and the opportunity to diagnose early and prevent progression of disease in patients of all ages. “It’s a small but mighty specialty,” said Dr. Hinshaw, associate professor of dermatology and section chief of dermatopathology at the University of Wisconsin–Madison.

It’s also a versatile specialty with a variety of subspecialties and niches to pursue – and women have been stepping in to fill unmet needs, Dr. Hinshaw said. “Women dermatologists are directing vulvar specialty clinics across the country, for example. There aren’t that many, but they’re filling an important niche. We have one at [our university] and it is packed.”

Women have also been drawn to the in-demand subspecialty of pediatric dermatology, she noted. They now make up more than two-thirds of all pediatric dermatologists, and many in practice have trained the old-fashioned way, completing two residencies. “That’s [involved] self-selection into an additional year of years training and a commitment to caring for special populations that, quite honestly, takes more time,” said Dr. Hinshaw, who, as part of her dermatology practice, runs a nail clinic at UW Health in Madison.

Amy S. Paller, MD, who chairs the department of dermatology at Northwestern University, Chicago, where she is professor of dermatology and pediatrics and directs the Skin Biology & Diseases Resource-Based Center, is one of these women. She took a long and determined journey into the subspecialty, encountering bias and discouragement while actively seeking out mentors who helped her advance.

Courtesy of Northwestern Memorial HealthCare

While in medical school at Stanford (Calif.) University in the late 1970s in a class “very progressively” made up of about one-third women, Dr. Paller met Alvin Jacobs, MD, who, in 1975, had founded the Society for Pediatric Dermatology. “There wasn’t much pediatric dermatology in the world at the time, and it was Al who helped [me realize] that it combined my love of genetic research with my [desire] to work with children,” she recalled.

Per Dr. Jacob’s advice, she went to Northwestern to train in both pediatrics and dermatology under Nancy Esterly, MD, who “is considered by many to be the mother of pediatric dermatology.” And knowing that she wanted to do research, Dr. Paller also worked with Ruth Freinkel, MD, who “was the strongest bench researcher” at Northwestern. (Dr. Freinkel had been one of the first female dermatology residents at Harvard and was the first full-time faculty member in dermatology at Northwestern).

After completing postdoctoral research at the University of North Carolina at Chapel Hill, Dr. Paller returned to Chicago and assumed Dr. Esterly’s position as chief of dermatology at the Children’s National Hospital of Chicago. It was there that “someone in a leadership position questioned me about how I could possibly be a scientist, a strong clinician, and a good mother to my three children – and suggested that I drop research,” Dr. Paller recalled.

“I think this person was trying to be helpful to me, but I was shocked,” she said. Just as Dr. Bergfeld had done, Dr. Paller channeled her frustration into new pursuits.

“It made me go home and think, how could I strengthen myself? What else could I do?” she said. “Soon after, with a highly supportive husband, I did a ‘pseudosabbatical,’ basically spending every ounce of spare time I had working with one of the premier female scientists in the country, Elaine Fuchs, and learning molecular biology” in her lab at the University of Chicago.

“I think we’ve all had discrimination along the way. Sometimes there’s implicit bias and sometimes there’s overt bias,” said Dr. Paller, who in 2004 led the society which her mentor Dr. Jacobs had founded several decades earlier. “I just jumped right in, and that’s enabled me to find good role models.”

Across dermatology broadly, the often holistic nature of the specialty – of the ability to peer into the body and its internal health – is another quality that women have been drawn to and advanced, Dr. Hinshaw said. “One of the reasons why I chose dermatology is because it’s a window to total patient health. Patients often see their dermatologists as physicians who help them identify next steps in their health care, who can help them address issues related to their overall health and well-being, including their mental health.”

In a WDS membership survey conducted in 2018, most respondents reported that they frequently or occasionally detect and diagnose systemic/internal diseases and conditions in their female patients, and that they consult and collaborate with different kinds of physicians (Int J Womens Dermatol. 2018 Nov 15;4[4]:189-92).

And in a March 2019 “Dialogues in Dermatology” podcast episode on the history and advancement of women in dermatology produced by the American Academy of Dermatology, Pearl Grimes, MD, a clinical professor of dermatology of the University of California, Los Angeles, and then-president of the WDS, described why “total women’s health” had become an additional focus for the society.

“We’re already gatekeepers” in many respects, Dr. Grimes said. “In addition to my addressing specific skin issues, my patients query me on hormone issues, on nutrition, on stress-related issues….and on [what other physicians they should see].”

Disparities in academia

Dermatology departments in academic medicine have burgeoned in size in the past 50 years, and women are well represented overall. In 2018, women comprised 51.2% of dermatology department faculty – up from 10.8% in 1970 – a current proportion that ranks fifth among specialties for the proportion of female faculty, according to a cross-sectional study of faculty diversity trends using data from the AAMC faculty roster (JAMA Dermatol. 2020 Jan 8;156[3]:280-7).

The AAMC data show the share of women dermatology faculty declining at each subsequent rank, however – a finding that suggests that women are not promoted as quickly or to the same levels of leadership as men, the report’s authors noted. (Dermatology isn’t alone: The AAMC issued a call to action on gender equity in medicine this year, citing this inverse association.)

Another recently published study of gender trends in academic dermatology – this one looking at a smaller sample of data from 15 institutions – similarly found that women dermatologists made up a majority of faculty (53.6%) and were well represented as assistant professors (60.7%) but underrepresented as full professors (17%).

This study differed from the larger AAMC study, however, in that it controlled for “achievement indicators” – career duration, publications per year, and National Institutes of Health research funding – and found that gender alone was not associated with higher rank. Instead, promotions were correlated most significantly with NIH research funding and also with career duration and publications per year.

“If research achievement is to be used as a benchmark for academic promotion, increased efforts are needed to support the research activities of women,” the authors wrote, adding that recognition should be given to other factors as well.

Dr. Paller and Dr. Hinshaw both described the situation as complex and multifaceted. Some research on promotion in academia in general – but not all – has suggested that women do need to publish more than men in order to be promoted. But “the promotion process also has within it the ability to use judgment [about] the impact and merits of work,” said Dr. Hinshaw. “Not all publications [and levels of authorship] may be considered equal, for instance.”

Dr. Hinshaw said she is also concerned by data showing that women still perform the majority of household duties, “even in households in which both partners work outside the home equivalently.” As long as this is the case, women may be “inherently disadvantaged” in their ability to have adequate research time and to advance.

From where she sits, Dr. Paller sees several factors at play: “The pipeline, achievement during the pipeline, and decision-making about advancement” on the part of women themselves. Having served on search committees for top leadership in specialties in which women are well represented, she said, “I’ve seen fewer women who’ve come forward and been interested in rising into a chair or a dean position.”

And “having talked to so many women,” Dr. Paller added, “I think there’s a phenomenon where it’s harder for women to accept positions [that require] a significant change.”

Women “are nurturers, which makes them extremely good [leaders] and chairs, but it also makes it harder to make life changes that affect the people they love,” she said, noting that becoming a department chair or a dean often involves moving. “I also think that women in general are happier and committed to what they’re [currently] doing.”

Dr. Paller is optimistic that, with the support of department chairs and continued attention to role modeling and mentoring, the portrait of women in academic dermatology will continue to improve. Currently, 34 chairs of dermatology departments are female, she noted. “That number was 11 less 15 years ago.”

In the meantime, researchers are increasingly documenting trends in women’s editorships of journals as well as leadership and speaking opportunities at professional conferences.

The authors of one study published this year, for instance, reviewed the editorial boards of dermatology journals and found that women occupied 18% of editor in chief roles, 36% of deputy editor positions, and 22% of overall editorial board roles (Int J Womens Dermatol. 2019 Sep 12;6[1]:20-4). Other research shows women comprising 43% of all authorships across 23 dermatologic journals from 2008 to May 2017, 50.2% of first authorships, and 33.1% of last authorships (BMJ Open. 2018 Apr 13;8[4]:e020089).

Both in academic medicine and in practice, a gender pay gap still affects women physicians across the board. Medscape’s 2020 dermatologist compensation report shows male dermatologists earning about 12% more than their female peers (average, $435,000 vs. $387,000, respectively), while the average number of hours per week spent seeing patients is similar (36.2 vs. 35.6 hours, respectively).

And in its 2020 statement on gender equity, the AAMC said that women in academic medicine are offered less in starting salary, negotiated pay, and other forms of compensation than men “despite equal effort, rank, training, and experience.”

It’s complicated to tease apart all the factors that may be involved – but important to keep challenging the system, said Dr. Bergfeld, who was a long-time board adviser for Dermatology News. “I was underpaid,” she noted, and “this was only rectified in the last 10 years.”

 

Work-life balance

In the AAD podcast on women in dermatology, Dr. Grimes said that achieving a healthy and balanced work life remains one of the greatest challenges for women dermatologists – and it may be even greater than in the past given the growing numbers of group practices. “When women enter the realm of group practice, they have less flexibility in controlling their time and their own schedules.”

If Anna Hare, MD, is any indication, younger dermatologists may buck this trend. The daughter of Dr. Rich in Portland, Dr. Hare joined her mother’s dermatology practice and research center knowing that she’d have “the respect and flexibility for deciding how I want to practice.”

Younger dermatologists, she said, place “more of an emphasis on work-life balance and quality of life.”

Fortunately, said Dr. Bergfeld, women have advanced enough in the ranks of dermatology that, in networking, in mentorship, and in workplace settings, attention can be paid more fully to discussions about work-life management – “how to manage your life when you’re working with family and kids and parents.”

In the 1970s, at the Cleveland Clinic, “there were only five women on staff and we were fighting for [basic] rights,” she said. “We wanted equality – we were [perceived as] little worker bees….We needed to climb as the men did to positions of leadership and address the problems of women.”

In pursuing their goals and making further progress, women dermatologists today should be “steady and calm,” she advised. Formally acquiring leadership skills and communication skills is a timeless need. And when there are biases or conflicts, “you cannot have righteous indignation, you cannot have revenge. You have to calm yourself and move forward.”

When Stephen Tyring, MD, PhD, an infectious disease dermatologist, started his career in the early 1980s, he said “we were diagnosing Kaposi’s sarcoma right and left. We would see a new case every day or two.”

It was the early days of the HIV/AIDS epidemic, and dermatologists were at the forefront because HIV/AIDS often presented with skin manifestations. Dr. Tyring, clinical professor in the departments of dermatology, microbiology & molecular genetics and internal medicine at the University of Texas Health Science Center, Houston, and his colleagues referred Kaposi’s patients for chemotherapy and radiation, but the outlook was often grim, especially if lesions developed in the lungs.

Dermatologist don’t see much Kaposi’s anymore because of highly effective treatments for HIV. It highlights one of the major advances in infectious disease (ID) dermatology since Dermatology News published its first issue under the name Skin & Allergy News in January 1970: improved management of viral disease.

Members of the original editorial advisory board saw it coming. In a feature in which board members provided their prediction for the 1970s that appeared in the first issue, New York dermatologist Norman Orentreich, MD, counted the “probable introduction of virucidal agents” as one of the “significant advances or changes that I foresee in the next 10 years.” J. Lamar Callaway, MD, professor of dermatology at Duke University, Durham, N.C., predicted that “the next 10 years should develop effective anti-viral agents for warts, herpes simplex, and herpes zoster.”

“A lot of advancements against herpes viruses”

One of the biggest wins for ID dermatology over the last 5 decades has been the management of herpes, both herpes simplex virus 1 and 2, as well as herpes zoster virus. It started with the approval of acyclovir in 1981. Before then, “we had no direct therapy for genital herpes, herpes zoster, or disseminated herpes in immunosuppressed or cancer patients,” Dr. Rosen said.

“I can remember doing an interview with Good Morning America when I gave the first IV dose of acyclovir in the city of Houston for really bad disseminated herpes” in an HIV patient, he said, and it worked.

Two derivatives, valacyclovir and famciclovir, became available in the mid-1990s, so today “we have three drugs and some others at the periphery that are all highly effective not only” against herpes, but also for preventing outbreaks; valacyclovir can even prevent asymptomatic shedding, therefore possibly preventing new infections. “That’s a concept we didn’t even have 40 years ago,” Dr. Rosen said.

Cidofovir has also made a difference. The IV formulation was approved for AIDS-associated cytomegalovirus retinitis in 1996 but discontinued a few years later amid concerns of severe renal toxicity. It’s found a new home in dermatology since then, explained ID dermatologist Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia.

Dermatologists see acyclovir-resistant herpes “heaped up on the genitals in HIV patients,” and there weren’t many options in the past. A few years ago, “we [tried] injecting cidofovir directly into the skin lesions, and it’s been remarkably successful. It is a good way to treat these lesions” if dermatologists can get it compounded, she said.

Shingles vaccines, first the live attenuated zoster vaccine (Zostavax) approved by the Food and Drug Administration in 2006 and the more effective recombinant zoster vaccine (Shingrix) approved in 2017, have also had a significant impact.

Dr. Rosen remembers what it was like when he first started practicing over 40 years ago. Not uncommonly, “we saw horrible cases of shingles,” including one in his uncle, who was left with permanent hand pain long after the rash subsided.

Today, “I see much less shingles, and when I do see it, it’s in a much-attenuated form. [Shingrix], even if it doesn’t prevent the disease, often prevents postherpetic neuralgia,” he said.

Also, with pediatric vaccinations against chicken pox, “we’re probably going to see a whole new generation without shingles, which is huge. We’ve made a lot of advancements against herpes viruses,” Dr. Kovarik said.
 

“We finally found something that helps”

“We’ve [also] come a really long way with genital wart treatment,” Dr. Kovarik said.

It started with approval of topical imiquimod in 1997. “Before that, we were just killing one wart here and one wart there” but they would often come back and pop up in other areas. Injectable interferon was an option at the time, but people didn’t like all the needles.

With imiquimod, “we finally [had] a way to target HPV [human papillomavirus] and not just scrape” or freeze one wart at a time, and “we were able to generate an inflammatory response in the whole area to clear the virus.” Working with HIV patients, “I see sheets and sheets of confluent warts throughout the whole genital area; to try to freeze that is impossible. Now I have a way to get rid of [genital] warts and keep them away even if you have a big cluster,” she said.

“Sometimes, we’ll do both liquid nitrogen and imiquimod. That’s a good way to tackle people who have a high burden of warts,” Dr. Kovarik noted. Other effective treatments have come out as well, including an ointment formulation of sinecatechins, extracted from green tea, “but you have to put it on several times a day, and insurance companies don’t cover it often,” she said.

Intralesional cidofovir is also proving to be boon for potentially malignant refractory warts in HIV and transplant patients. “It’s an incredible treatment. We can inject that antiviral into warts and get rid of them. We finally found something that helps” these people, Dr. Kovarik said.

The HPV vaccine Gardasil is making a difference, as well. In addition to cervical dysplasia and anogenital cancers, it protects against two condyloma strains. Dr. Rosen said he’s seeing fewer cases of genital warts now than when he started practicing, likely because of the vaccine.
 

“Organisms that weren’t pathogens are now pathogens”

Antibiotic resistance probably tops the list for what’s changed in a bad way in ID dermatology since 1970. Dr. Rosen remembers at the start of his career that “we never worried about antibiotic resistance. We’d put people on antibiotics for acne, rosacea, and we’d keep them on them for 3 years, 6 years”; resistance wasn’t on the radar screen and was not mentioned once in the first issue of Dermatology News, which was packed with articles and ran 24 pages.

The situation is different now. Driven by decades of overuse in agriculture and the medical system, antibiotic resistance is a concern throughout medicine, and unfortunately, “we have not come nearly as far as fast with antibiotics,” at least the ones dermatologists use, “as we have with antivirals,” Dr. Tyring said.

For instance, methicillin-resistant Staphylococcus aureus (MRSA), first described in the United States in 1968, is “no longer the exception to the rule, but the rule” itself, he said, with carbuncles, furuncles, and abscesses not infrequently growing out MRSA. There are also new drug-resistant forms of old problems like gonorrhea and tuberculosis, among other developments, and impetigo has shifted since 1970 from mostly a Streptococcus infection easily treated with penicillin to often a Staphylococcus disease that’s resistant to it. There’s also been a steady march of new pathogens, including the latest one, SARS-CoV-2, the virus that causes COVID-19, which has been recognized as having a variety of skin manifestations.

“No matter how smart we think we are, nature has a way of putting us back in our place,” Dr. Rosen said.

The bright spot is that “we’ve become very adept at identifying and characterizing” microbes “based on techniques we didn’t even have when I started practicing,” such as polymerase chain reaction. “It has taken a lot of guess work out of treating infectious diseases,” he said.

The widespread use of immunosuppressives such as cyclophosphamide, mycophenolate, azathioprine, rituximab, and other agents used in conjunction with solid organ transplantation, has also been a challenge. “We are seeing infections with really odd organisms. Just recently, I had a patient with fusarium in the skin; it’s a fungus that lives in the dirt. I saw a patient with a species of algae” that normally lives in stagnant water, he commented. “We used to get [things like that] back on reports, and we’d throw them away. You can’t do that anymore. Organisms that weren’t pathogens in the past are now pathogens,” particularly in immunosuppressed people, Dr. Rosen said.
 

Venereologists no more

There’s been another big change in the field. “Back in the not too distant past, dermatologists in the U.S. were referred to as ‘dermatologist-venereologists.’ ” It goes back to the time when syphilis wasn’t diagnosed and treated early, so patients often presented with secondary skin complications and went to dermatologists for help. As a result, “dermatologists became the most experienced at treating it,” Dr. Tyring said.

That’s faded from practice. Part of the reason is that as late as 2000, syphilis seemed to be on the way out; the Centers for Disease and Control and Prevention even raised the possibility of elimination. Dermatologists turned their attention to other areas.

It might have been short-sighted, Dr. Rosen said. Syphilis has made a strong comeback, and drug-resistant gonorrhea has also emerged globally and in at least a few states. No other medical field has stepped in to take up the slack. “Ob.gyns. are busy delivering babies, ID [physicians are] concerned about HIV, and urologists are worried about kidney stones and cancer.” Other than herpes and genital warts, “we have not done well” with management of sexually transmitted diseases, he said.
 

“I could sense” his frustration

The first issue of Dermatology News carried an article and photospread about scabies that could run today, except that topical permethrin and oral ivermectin have largely replaced benzyl benzoate and sulfur ointments for treatment in the United States. In the article, Scottish dermatologist J. O’D. Alexander, MD, called scabies “the scourge of mankind” and blamed it’s prevalence on “an offhand attitude to the disease which makes control very difficult.”

“I could sense this man’s frustration that people were not recognizing scabies,” Dr. Kovarik said, and it’s no closer to being eradicated than it was in 1970. “It’s still around, and we see it in our clinics. It’s a horrible disease in kids we see in dermatology not infrequently,” and treatment has only advanced a bit.

The article highlights what hasn’t changed much in ID dermatology over the years. Common warts are another one. “With all the evolution in medicine, we don’t have any better treatments approved for common warts than we ever had.” Injecting cidofovir “works great,” but access is a problem, Dr. Tyring said.

Onychomycosis has also proven a tough nut to crack. Readers back in 1970 counted the introduction of the antifungal, griseofulvin, as a major advancement in the 1960s; it’s still a go-to for tinea capitis, but it didn’t work very well for toenail fungus. Terbinafine (Lamisil), approved in 1993, and subsequent developments have helped, but the field still awaits more effective options; a few potential new agents are in the pipeline.

Although there have been major advancements for serious systemic fungal infections, “we’ve mainly seen small steps forward” in ID dermatology, Dr. Tyring said.

Dr. Tyring, Dr. Kovarik, and Dr. Rosen said they had no relevant disclosures.

[email protected]

When Stephen Tyring, MD, PhD, an infectious disease dermatologist, started his career in the early 1980s, he said “we were diagnosing Kaposi’s sarcoma right and left. We would see a new case every day or two.”

It was the early days of the HIV/AIDS epidemic, and dermatologists were at the forefront because HIV/AIDS often presented with skin manifestations. Dr. Tyring, clinical professor in the departments of dermatology, microbiology & molecular genetics and internal medicine at the University of Texas Health Science Center, Houston, and his colleagues referred Kaposi’s patients for chemotherapy and radiation, but the outlook was often grim, especially if lesions developed in the lungs.

Dermatologist don’t see much Kaposi’s anymore because of highly effective treatments for HIV. It highlights one of the major advances in infectious disease (ID) dermatology since Dermatology News published its first issue under the name Skin & Allergy News in January 1970: improved management of viral disease.

Members of the original editorial advisory board saw it coming. In a feature in which board members provided their prediction for the 1970s that appeared in the first issue, New York dermatologist Norman Orentreich, MD, counted the “probable introduction of virucidal agents” as one of the “significant advances or changes that I foresee in the next 10 years.” J. Lamar Callaway, MD, professor of dermatology at Duke University, Durham, N.C., predicted that “the next 10 years should develop effective anti-viral agents for warts, herpes simplex, and herpes zoster.”

“A lot of advancements against herpes viruses”

One of the biggest wins for ID dermatology over the last 5 decades has been the management of herpes, both herpes simplex virus 1 and 2, as well as herpes zoster virus. It started with the approval of acyclovir in 1981. Before then, “we had no direct therapy for genital herpes, herpes zoster, or disseminated herpes in immunosuppressed or cancer patients,” Dr. Rosen said.

“I can remember doing an interview with Good Morning America when I gave the first IV dose of acyclovir in the city of Houston for really bad disseminated herpes” in an HIV patient, he said, and it worked.

Two derivatives, valacyclovir and famciclovir, became available in the mid-1990s, so today “we have three drugs and some others at the periphery that are all highly effective not only” against herpes, but also for preventing outbreaks; valacyclovir can even prevent asymptomatic shedding, therefore possibly preventing new infections. “That’s a concept we didn’t even have 40 years ago,” Dr. Rosen said.

Cidofovir has also made a difference. The IV formulation was approved for AIDS-associated cytomegalovirus retinitis in 1996 but discontinued a few years later amid concerns of severe renal toxicity. It’s found a new home in dermatology since then, explained ID dermatologist Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia.

Dermatologists see acyclovir-resistant herpes “heaped up on the genitals in HIV patients,” and there weren’t many options in the past. A few years ago, “we [tried] injecting cidofovir directly into the skin lesions, and it’s been remarkably successful. It is a good way to treat these lesions” if dermatologists can get it compounded, she said.

Shingles vaccines, first the live attenuated zoster vaccine (Zostavax) approved by the Food and Drug Administration in 2006 and the more effective recombinant zoster vaccine (Shingrix) approved in 2017, have also had a significant impact.

Dr. Rosen remembers what it was like when he first started practicing over 40 years ago. Not uncommonly, “we saw horrible cases of shingles,” including one in his uncle, who was left with permanent hand pain long after the rash subsided.

Today, “I see much less shingles, and when I do see it, it’s in a much-attenuated form. [Shingrix], even if it doesn’t prevent the disease, often prevents postherpetic neuralgia,” he said.

Also, with pediatric vaccinations against chicken pox, “we’re probably going to see a whole new generation without shingles, which is huge. We’ve made a lot of advancements against herpes viruses,” Dr. Kovarik said.
 

“We finally found something that helps”

“We’ve [also] come a really long way with genital wart treatment,” Dr. Kovarik said.

It started with approval of topical imiquimod in 1997. “Before that, we were just killing one wart here and one wart there” but they would often come back and pop up in other areas. Injectable interferon was an option at the time, but people didn’t like all the needles.

With imiquimod, “we finally [had] a way to target HPV [human papillomavirus] and not just scrape” or freeze one wart at a time, and “we were able to generate an inflammatory response in the whole area to clear the virus.” Working with HIV patients, “I see sheets and sheets of confluent warts throughout the whole genital area; to try to freeze that is impossible. Now I have a way to get rid of [genital] warts and keep them away even if you have a big cluster,” she said.

“Sometimes, we’ll do both liquid nitrogen and imiquimod. That’s a good way to tackle people who have a high burden of warts,” Dr. Kovarik noted. Other effective treatments have come out as well, including an ointment formulation of sinecatechins, extracted from green tea, “but you have to put it on several times a day, and insurance companies don’t cover it often,” she said.

Intralesional cidofovir is also proving to be boon for potentially malignant refractory warts in HIV and transplant patients. “It’s an incredible treatment. We can inject that antiviral into warts and get rid of them. We finally found something that helps” these people, Dr. Kovarik said.

The HPV vaccine Gardasil is making a difference, as well. In addition to cervical dysplasia and anogenital cancers, it protects against two condyloma strains. Dr. Rosen said he’s seeing fewer cases of genital warts now than when he started practicing, likely because of the vaccine.
 

“Organisms that weren’t pathogens are now pathogens”

Antibiotic resistance probably tops the list for what’s changed in a bad way in ID dermatology since 1970. Dr. Rosen remembers at the start of his career that “we never worried about antibiotic resistance. We’d put people on antibiotics for acne, rosacea, and we’d keep them on them for 3 years, 6 years”; resistance wasn’t on the radar screen and was not mentioned once in the first issue of Dermatology News, which was packed with articles and ran 24 pages.

The situation is different now. Driven by decades of overuse in agriculture and the medical system, antibiotic resistance is a concern throughout medicine, and unfortunately, “we have not come nearly as far as fast with antibiotics,” at least the ones dermatologists use, “as we have with antivirals,” Dr. Tyring said.

For instance, methicillin-resistant Staphylococcus aureus (MRSA), first described in the United States in 1968, is “no longer the exception to the rule, but the rule” itself, he said, with carbuncles, furuncles, and abscesses not infrequently growing out MRSA. There are also new drug-resistant forms of old problems like gonorrhea and tuberculosis, among other developments, and impetigo has shifted since 1970 from mostly a Streptococcus infection easily treated with penicillin to often a Staphylococcus disease that’s resistant to it. There’s also been a steady march of new pathogens, including the latest one, SARS-CoV-2, the virus that causes COVID-19, which has been recognized as having a variety of skin manifestations.

“No matter how smart we think we are, nature has a way of putting us back in our place,” Dr. Rosen said.

The bright spot is that “we’ve become very adept at identifying and characterizing” microbes “based on techniques we didn’t even have when I started practicing,” such as polymerase chain reaction. “It has taken a lot of guess work out of treating infectious diseases,” he said.

The widespread use of immunosuppressives such as cyclophosphamide, mycophenolate, azathioprine, rituximab, and other agents used in conjunction with solid organ transplantation, has also been a challenge. “We are seeing infections with really odd organisms. Just recently, I had a patient with fusarium in the skin; it’s a fungus that lives in the dirt. I saw a patient with a species of algae” that normally lives in stagnant water, he commented. “We used to get [things like that] back on reports, and we’d throw them away. You can’t do that anymore. Organisms that weren’t pathogens in the past are now pathogens,” particularly in immunosuppressed people, Dr. Rosen said.
 

Venereologists no more

There’s been another big change in the field. “Back in the not too distant past, dermatologists in the U.S. were referred to as ‘dermatologist-venereologists.’ ” It goes back to the time when syphilis wasn’t diagnosed and treated early, so patients often presented with secondary skin complications and went to dermatologists for help. As a result, “dermatologists became the most experienced at treating it,” Dr. Tyring said.

That’s faded from practice. Part of the reason is that as late as 2000, syphilis seemed to be on the way out; the Centers for Disease and Control and Prevention even raised the possibility of elimination. Dermatologists turned their attention to other areas.

It might have been short-sighted, Dr. Rosen said. Syphilis has made a strong comeback, and drug-resistant gonorrhea has also emerged globally and in at least a few states. No other medical field has stepped in to take up the slack. “Ob.gyns. are busy delivering babies, ID [physicians are] concerned about HIV, and urologists are worried about kidney stones and cancer.” Other than herpes and genital warts, “we have not done well” with management of sexually transmitted diseases, he said.
 

“I could sense” his frustration

The first issue of Dermatology News carried an article and photospread about scabies that could run today, except that topical permethrin and oral ivermectin have largely replaced benzyl benzoate and sulfur ointments for treatment in the United States. In the article, Scottish dermatologist J. O’D. Alexander, MD, called scabies “the scourge of mankind” and blamed it’s prevalence on “an offhand attitude to the disease which makes control very difficult.”

“I could sense this man’s frustration that people were not recognizing scabies,” Dr. Kovarik said, and it’s no closer to being eradicated than it was in 1970. “It’s still around, and we see it in our clinics. It’s a horrible disease in kids we see in dermatology not infrequently,” and treatment has only advanced a bit.

The article highlights what hasn’t changed much in ID dermatology over the years. Common warts are another one. “With all the evolution in medicine, we don’t have any better treatments approved for common warts than we ever had.” Injecting cidofovir “works great,” but access is a problem, Dr. Tyring said.

Onychomycosis has also proven a tough nut to crack. Readers back in 1970 counted the introduction of the antifungal, griseofulvin, as a major advancement in the 1960s; it’s still a go-to for tinea capitis, but it didn’t work very well for toenail fungus. Terbinafine (Lamisil), approved in 1993, and subsequent developments have helped, but the field still awaits more effective options; a few potential new agents are in the pipeline.

Although there have been major advancements for serious systemic fungal infections, “we’ve mainly seen small steps forward” in ID dermatology, Dr. Tyring said.

Dr. Tyring, Dr. Kovarik, and Dr. Rosen said they had no relevant disclosures.

[email protected]

When Stephen Tyring, MD, PhD, an infectious disease dermatologist, started his career in the early 1980s, he said “we were diagnosing Kaposi’s sarcoma right and left. We would see a new case every day or two.”

It was the early days of the HIV/AIDS epidemic, and dermatologists were at the forefront because HIV/AIDS often presented with skin manifestations. Dr. Tyring, clinical professor in the departments of dermatology, microbiology & molecular genetics and internal medicine at the University of Texas Health Science Center, Houston, and his colleagues referred Kaposi’s patients for chemotherapy and radiation, but the outlook was often grim, especially if lesions developed in the lungs.

Dermatologist don’t see much Kaposi’s anymore because of highly effective treatments for HIV. It highlights one of the major advances in infectious disease (ID) dermatology since Dermatology News published its first issue under the name Skin & Allergy News in January 1970: improved management of viral disease.

Members of the original editorial advisory board saw it coming. In a feature in which board members provided their prediction for the 1970s that appeared in the first issue, New York dermatologist Norman Orentreich, MD, counted the “probable introduction of virucidal agents” as one of the “significant advances or changes that I foresee in the next 10 years.” J. Lamar Callaway, MD, professor of dermatology at Duke University, Durham, N.C., predicted that “the next 10 years should develop effective anti-viral agents for warts, herpes simplex, and herpes zoster.”

“A lot of advancements against herpes viruses”

One of the biggest wins for ID dermatology over the last 5 decades has been the management of herpes, both herpes simplex virus 1 and 2, as well as herpes zoster virus. It started with the approval of acyclovir in 1981. Before then, “we had no direct therapy for genital herpes, herpes zoster, or disseminated herpes in immunosuppressed or cancer patients,” Dr. Rosen said.

“I can remember doing an interview with Good Morning America when I gave the first IV dose of acyclovir in the city of Houston for really bad disseminated herpes” in an HIV patient, he said, and it worked.

Two derivatives, valacyclovir and famciclovir, became available in the mid-1990s, so today “we have three drugs and some others at the periphery that are all highly effective not only” against herpes, but also for preventing outbreaks; valacyclovir can even prevent asymptomatic shedding, therefore possibly preventing new infections. “That’s a concept we didn’t even have 40 years ago,” Dr. Rosen said.

Cidofovir has also made a difference. The IV formulation was approved for AIDS-associated cytomegalovirus retinitis in 1996 but discontinued a few years later amid concerns of severe renal toxicity. It’s found a new home in dermatology since then, explained ID dermatologist Carrie Kovarik, MD, associate professor of dermatology at the University of Pennsylvania, Philadelphia.

Dermatologists see acyclovir-resistant herpes “heaped up on the genitals in HIV patients,” and there weren’t many options in the past. A few years ago, “we [tried] injecting cidofovir directly into the skin lesions, and it’s been remarkably successful. It is a good way to treat these lesions” if dermatologists can get it compounded, she said.

Shingles vaccines, first the live attenuated zoster vaccine (Zostavax) approved by the Food and Drug Administration in 2006 and the more effective recombinant zoster vaccine (Shingrix) approved in 2017, have also had a significant impact.

Dr. Rosen remembers what it was like when he first started practicing over 40 years ago. Not uncommonly, “we saw horrible cases of shingles,” including one in his uncle, who was left with permanent hand pain long after the rash subsided.

Today, “I see much less shingles, and when I do see it, it’s in a much-attenuated form. [Shingrix], even if it doesn’t prevent the disease, often prevents postherpetic neuralgia,” he said.

Also, with pediatric vaccinations against chicken pox, “we’re probably going to see a whole new generation without shingles, which is huge. We’ve made a lot of advancements against herpes viruses,” Dr. Kovarik said.
 

“We finally found something that helps”

“We’ve [also] come a really long way with genital wart treatment,” Dr. Kovarik said.

It started with approval of topical imiquimod in 1997. “Before that, we were just killing one wart here and one wart there” but they would often come back and pop up in other areas. Injectable interferon was an option at the time, but people didn’t like all the needles.

With imiquimod, “we finally [had] a way to target HPV [human papillomavirus] and not just scrape” or freeze one wart at a time, and “we were able to generate an inflammatory response in the whole area to clear the virus.” Working with HIV patients, “I see sheets and sheets of confluent warts throughout the whole genital area; to try to freeze that is impossible. Now I have a way to get rid of [genital] warts and keep them away even if you have a big cluster,” she said.

“Sometimes, we’ll do both liquid nitrogen and imiquimod. That’s a good way to tackle people who have a high burden of warts,” Dr. Kovarik noted. Other effective treatments have come out as well, including an ointment formulation of sinecatechins, extracted from green tea, “but you have to put it on several times a day, and insurance companies don’t cover it often,” she said.

Intralesional cidofovir is also proving to be boon for potentially malignant refractory warts in HIV and transplant patients. “It’s an incredible treatment. We can inject that antiviral into warts and get rid of them. We finally found something that helps” these people, Dr. Kovarik said.

The HPV vaccine Gardasil is making a difference, as well. In addition to cervical dysplasia and anogenital cancers, it protects against two condyloma strains. Dr. Rosen said he’s seeing fewer cases of genital warts now than when he started practicing, likely because of the vaccine.
 

“Organisms that weren’t pathogens are now pathogens”

Antibiotic resistance probably tops the list for what’s changed in a bad way in ID dermatology since 1970. Dr. Rosen remembers at the start of his career that “we never worried about antibiotic resistance. We’d put people on antibiotics for acne, rosacea, and we’d keep them on them for 3 years, 6 years”; resistance wasn’t on the radar screen and was not mentioned once in the first issue of Dermatology News, which was packed with articles and ran 24 pages.

The situation is different now. Driven by decades of overuse in agriculture and the medical system, antibiotic resistance is a concern throughout medicine, and unfortunately, “we have not come nearly as far as fast with antibiotics,” at least the ones dermatologists use, “as we have with antivirals,” Dr. Tyring said.

For instance, methicillin-resistant Staphylococcus aureus (MRSA), first described in the United States in 1968, is “no longer the exception to the rule, but the rule” itself, he said, with carbuncles, furuncles, and abscesses not infrequently growing out MRSA. There are also new drug-resistant forms of old problems like gonorrhea and tuberculosis, among other developments, and impetigo has shifted since 1970 from mostly a Streptococcus infection easily treated with penicillin to often a Staphylococcus disease that’s resistant to it. There’s also been a steady march of new pathogens, including the latest one, SARS-CoV-2, the virus that causes COVID-19, which has been recognized as having a variety of skin manifestations.

“No matter how smart we think we are, nature has a way of putting us back in our place,” Dr. Rosen said.

The bright spot is that “we’ve become very adept at identifying and characterizing” microbes “based on techniques we didn’t even have when I started practicing,” such as polymerase chain reaction. “It has taken a lot of guess work out of treating infectious diseases,” he said.

The widespread use of immunosuppressives such as cyclophosphamide, mycophenolate, azathioprine, rituximab, and other agents used in conjunction with solid organ transplantation, has also been a challenge. “We are seeing infections with really odd organisms. Just recently, I had a patient with fusarium in the skin; it’s a fungus that lives in the dirt. I saw a patient with a species of algae” that normally lives in stagnant water, he commented. “We used to get [things like that] back on reports, and we’d throw them away. You can’t do that anymore. Organisms that weren’t pathogens in the past are now pathogens,” particularly in immunosuppressed people, Dr. Rosen said.
 

Venereologists no more

There’s been another big change in the field. “Back in the not too distant past, dermatologists in the U.S. were referred to as ‘dermatologist-venereologists.’ ” It goes back to the time when syphilis wasn’t diagnosed and treated early, so patients often presented with secondary skin complications and went to dermatologists for help. As a result, “dermatologists became the most experienced at treating it,” Dr. Tyring said.

That’s faded from practice. Part of the reason is that as late as 2000, syphilis seemed to be on the way out; the Centers for Disease and Control and Prevention even raised the possibility of elimination. Dermatologists turned their attention to other areas.

It might have been short-sighted, Dr. Rosen said. Syphilis has made a strong comeback, and drug-resistant gonorrhea has also emerged globally and in at least a few states. No other medical field has stepped in to take up the slack. “Ob.gyns. are busy delivering babies, ID [physicians are] concerned about HIV, and urologists are worried about kidney stones and cancer.” Other than herpes and genital warts, “we have not done well” with management of sexually transmitted diseases, he said.
 

“I could sense” his frustration

The first issue of Dermatology News carried an article and photospread about scabies that could run today, except that topical permethrin and oral ivermectin have largely replaced benzyl benzoate and sulfur ointments for treatment in the United States. In the article, Scottish dermatologist J. O’D. Alexander, MD, called scabies “the scourge of mankind” and blamed it’s prevalence on “an offhand attitude to the disease which makes control very difficult.”

“I could sense this man’s frustration that people were not recognizing scabies,” Dr. Kovarik said, and it’s no closer to being eradicated than it was in 1970. “It’s still around, and we see it in our clinics. It’s a horrible disease in kids we see in dermatology not infrequently,” and treatment has only advanced a bit.

The article highlights what hasn’t changed much in ID dermatology over the years. Common warts are another one. “With all the evolution in medicine, we don’t have any better treatments approved for common warts than we ever had.” Injecting cidofovir “works great,” but access is a problem, Dr. Tyring said.

Onychomycosis has also proven a tough nut to crack. Readers back in 1970 counted the introduction of the antifungal, griseofulvin, as a major advancement in the 1960s; it’s still a go-to for tinea capitis, but it didn’t work very well for toenail fungus. Terbinafine (Lamisil), approved in 1993, and subsequent developments have helped, but the field still awaits more effective options; a few potential new agents are in the pipeline.

Although there have been major advancements for serious systemic fungal infections, “we’ve mainly seen small steps forward” in ID dermatology, Dr. Tyring said.

Dr. Tyring, Dr. Kovarik, and Dr. Rosen said they had no relevant disclosures.

[email protected]

For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.

“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”

Much has changed. Knowledge about the pathophysiology of dermatologic diseases has exponentially increased, largely because of basic and translational research by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.

Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.

This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.

Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.

Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”

Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.


 

The new frontier of atopic dermatitis

The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”

As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.

But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”

Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.

“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.

Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”

Bruce Jancin/MDedge News

Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.

“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”

Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.

“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”

Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.

“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”

Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.

JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”

Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.

In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
 

Spillover to other diseases

JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.

“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”

Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.

“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”

Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
 

Action on rare skin diseases

Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.

According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).

Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.

Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.

“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.

While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.

Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.

Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”

Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.

 

For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.

“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”

Much has changed. Knowledge about the pathophysiology of dermatologic diseases has exponentially increased, largely because of basic and translational research by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.

Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.

This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.

Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.

Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”

Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.


 

The new frontier of atopic dermatitis

The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”

As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.

But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”

Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.

“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.

Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”

Bruce Jancin/MDedge News

Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.

“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”

Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.

“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”

Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.

“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”

Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.

JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”

Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.

In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
 

Spillover to other diseases

JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.

“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”

Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.

“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”

Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
 

Action on rare skin diseases

Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.

According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).

Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.

Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.

“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.

While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.

Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.

Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”

Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.

 

For much of the past 50 years, many of the drugs used in dermatology have been adopted – and often adapted – from other specialties and used for dermatologic conditions.

“Almost every drug was more or less a hand-me-down” developed first for cancer or other diseases and found later, often serendipitously, to be useful for the skin, said William Eaglstein, MD, thinking back to the 1970s and recalling steroids, tetracyclines, methotrexate, and 5-flourouracil. “The perception always was that skin diseases weren’t serious, that the market was small.”

Much has changed. Knowledge about the pathophysiology of dermatologic diseases has exponentially increased, largely because of basic and translational research by dermatologist investigators, and “more and more companies are recognizing the importance of our diseases and the ability to get a return on investment,” said Dr. Eaglstein, past professor and chair of the departments of dermatology at the University of Miami and the University of Pittsburgh, who worked in industry after his academic career.

Psoriasis was a game changer, he and other dermatologists said in interviews. The tumor necrosis factor (TNF)–alpha blockers were first used for other indications, but their marked follow-on success in psoriasis “offered proof of concept clinically – showing that by targeting immune pathways in the skin we could achieve a clinical effect – and proof of concept commercially” that dermatology drugs are worth pursuing by pharmaceutical companies, said William Ju, MD, a cofounder and president of Advancing Innovation in Dermatology, a nonprofit organization that brings together stakeholders to develop novel dermatologic drugs and products.

This resulted in the approval of subsequent biologics, such as ustekinumab (Stelara) which inhibits the signaling of interleukin (IL)–12/IL-23, for psoriasis as their initial indication. Then, biologics targeting IL-17 followed this dermatology-first approach. “Researchers have continued further dissecting out the immunopathological pathways, and antibody drugs targeting IL-23p19 have been approved for psoriasis as the lead indication,” said Dr. Ju, a dermatologist who has worked in industry.

Seth Orlow, MD, PhD, who chairs the department of dermatology at NYU Langone Health, remembers the 1970s through the 1990s as the “era of topicals” developed for dermatologic conditions – topical antifungals, topical corticosteroids, and topical retinoids. The next decade was characterized by formulation tweaks and few novel treatments for dermatology, said Dr. Orlow, who is also professor of pediatric dermatology and director of the program in cutaneous biology at New York University.

Now, given the succession of psoriasis discoveries in the last decade, “large companies are interested in dermatology,” he said in an interview. “There’s an explosion of interest in atopic dermatitis. … and companies are dipping their toes in the water for alopecia areata and vitiligo. That’s amazing.”

Rare diseases like epidermolysis bullosa, ichthyosis, and basal cell nevus syndrome are getting attention as well, boosted by the Orphan Drug Act of 1983, in addition to increased research on disease pathways and growing appreciation of skin diseases. “There’s a lot under development, from small molecules to biologics to gene-based therapies,” Dr. Orlow commented.


 

The new frontier of atopic dermatitis

The approval in 2017 of dupilumab (Dupixent), a monoclonal antibody that inhibits the signaling of both IL-4 and IL-13) for moderate-severe atopic dermatitis (AD) in adults illustrates the new standing of dermatologic diseases in the field of drug development and commercialization. “Atopic dermatitis had always been the forgotten chronic disease in dermatology. … We’ve had no good treatments,” said Eric Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland. “Dupilumab coming to the forefront [as a dermatology-first indication] has changed the entire perspective of the field. … Everyone is now trying to find the next best drug.”

As with psoriasis, a targeted therapy for AD was made possible by the development in the 1990s of monoclonal antibody technology and the ensuing ability to create biologics that target specific molecules in the body – as well as bedside-to-bench research that homed in on the involvement of particular cytokines.

But there also is a “new understanding of the burden of the disease,” Dr. Simpson observed. In the last 5 years, he said, research funded by the National Eczema Association documented that AD “not only causes inflammation of the skin … but that it affects people at school and in the workplace, that people have multiple mental health comorbidities and skin infections, and that the disease profoundly affects the entire patient in ways that weren’t really recognized or appreciated.”

Having evolved in the footsteps of psoriasis, AD is at a higher starting point in terms of the safety and efficacy of its first biologic, sources said. On the other hand, AD is a much more complex and heterogeneous disease, and researchers are trying to determine which immune pathways and cytokines are most important – and in which populations.

“We’re at the beginning. We’re trying to figure out how to get 80% of patients clear or almost clear [as we can now with psoriasis biologics] rather than almost 40% [as in the dupilumab pivotal trials],” said Dr. Simpson, former cochair of the National Eczema Association’s scientific committee. Public data from ongoing phase 2 and 3 trials of other Th2 cytokine inhibitors suggest that 25%-45% of enrolled patients achieve high levels of clearance, he noted.

Emma Guttman-Yassky, MD, PhD, Sol and Clara Kest Professor and vice-chair for research in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said that AD’s heterogeneity involves “many factors, like ethnicity, age … and whether they have an atopic background such as asthma.”

Bruce Jancin/MDedge News

Her research is showing, for instance, that AD in Asian and black patients is different than AD in European-American patients, and that the presence of comorbidities may well have treatment implications. She has also shown that children may have a different phenotype than adults, with greater activation of the Th17 axis that typifies psoriasis.

“For certain patients, we may need to target more than one pathway, or target a different pathway than the Th2 pathway. And treatment may be different in the setting of comorbidities,” said Dr. Guttman-Yassky, who is also director of the laboratory of inflammatory skin diseases at Mount Sinai. “We may think of one treatment – dupilumab, for example – for someone who has asthma and AD. But for patients who don’t have asthma and are Asian, for instance, or for children, we may need additional agents.”

Her research over the years on AD has taught her the importance of human studies over mouse model studies; it was in humans, she noted, that she and other investigators demonstrated “without doubt” that AD is an immune disease and not simply a barrier disease. The Th2 cytokine pathway appears to play the predominant role in AD, though “there still is a strong Th1 component,” she said.

“We’re in a better position to figure this out today [than in the past 20 or even 10 years],” said Dr. Guttman-Yassky, who recalls being told years ago that AD was a “dead end,” that it “would kill [her] career.” Given the evolution of science and the recognition of comorbidities and seriousness of dermatologic diseases, “the stars are aligned to get more [therapies] to these patients.”

Janus kinase (JAK) inhibitors are among these therapies. Three JAK inhibitors are in or have recently completed phase 3 studies for AD; two are currently approved for rheumatoid arthritis, and the other has been designed specifically for AD, Dr. Simpson pointed out. The drugs are oral small molecule drugs that block the JAK signaling pathways for certain proinflammatory cytokines.

“The JAK inhibitors are a real exciting story for dermatology,” he said. “Theoretically, by blocking more cytokines than biologics do, there could be some safety issues – that’s why we’re awaiting big phase 3 study results so we can figure out the risk-benefit balance and guide our patients as to which drug is best.”

Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center in Portland – a stand-alone dermatology clinical trial center founded in 1998 – likes to envision the evolution of drugs for dermatologic conditions as a funnel, with the most broad-acting drugs at the wide top of the funnel and the most targeted drugs at the bottom tip.

JAK inhibitors, he said, sit near the middle – more targeted and safer than cyclosporine and methotrexate, for instance, but not as targeted as the biologics now available for psoriasis and being developed for AD. “The oral medications that have been developed for psoriasis and those coming for AD are not quite as targeted to the disease,” he noted. “JAK inhibitors have great efficacy – it’s more a question of safety and being able to treat without causing collateral damage.”

Dr. Blauvelt expects the armamentarium of new drugs approved for AD to go from one (dupilumab) to seven within the next 2 years. This will include three new biologics and three new oral JAK inhibitors, he predicts. As the specialty sorts through and integrates these new drugs into practice, dermatologists will increasingly personalize treatment and will face the “nonscientific” challenge of the cost of new therapies and patient access to them, he noted.

In the meantime, said Dr. Simpson, recent drug discoveries have driven more non–pharmaceutical-funded translational research aimed at understanding the underlying biology of AD. The National Institutes of Health, for instance, “is interested in dupilumab and its impact on the skin barrier and skin defense mechanisms,” he said. “We’ll learn a lot more [in coming years].”
 

Spillover to other diseases

JAK inhibitors – some in oral and some in topical form – are showing efficacy in ongoing research for alopecia areata (AA) and vitiligo as well, Dr. Blauvelt said.

“We’re understanding more about the pathophysiology of these diseases, which historically have been tough diseases for dermatologists to treat,” he said. “The successes in alopecia areata and vitiligo are incredibly exciting actually – it’s very exciting to see hair and pigment coming back. And as we learn more, we should be able to develop [additional] drugs that are more disease targeted than the JAK inhibitors.”

Already, some of the biologics used to treat psoriasis have been studied in patients with hidradenitis suppurativa (HS), a disease in which painful lumps and sometimes tunnels form under the skin, with some success; adalimumab (Humira), a TNF-inhibitor, is now FDA approved for the treatment of moderate-severe HS, and studies are ongoing of IL-17 and IL-23 blockers for the disease.

“The pathophysiology [of HS] is very complex; it’s not nearly as straightforward as psoriasis, and there haven’t been any major breakthroughs yet,” Dr. Blauvelt said. “But the drugs seem to be working better than historical alternatives.”

Regarding AA, Dr. Guttman-Yassky, who is participating in a study of dupilumab for AA, recently found in a retrospective cross-sectional study that patients with the condition are more likely to have atopic comorbidities – asthma, allergic rhinitis, and AD, for instance. “The more comorbid conditions, the greater the risk of developing alopecia areata,” she said. “That could point to a potential pathogenic role of the Th2 axis in the disorder [challenging the traditional view of AA as a singularly Th1-centered disease.] The future will tell.”
 

Action on rare skin diseases

Both large and small companies have moved into the orphan drug space, investing in research and pursuing orphan drug indications for dermatologic conditions, because “it’s clear now in the marketplace that companies can develop effective drugs for rare disorders and be quite successful,” Dr. Orlow said.

According to a recent analysis, as a result of incentives for rare disease drug development contained in the Orphan Drug Act, 72 indications have been approved for rare skin disease, skin-related cancers, and hereditary disorders with prominent dermatologic manifestations since the law was passed in 1983 (J. Am. Acad. Dermatol. 2019;81[3]:867-77).

Epidermolysis bullosa (EB) is a good example, he and other sources said, of commercial interests merging with growing knowledge of disease pathogenesis as well as the tools needed to develop new treatments.

Research by dermatology scientists and others over the past 40 years, Dr. Ju explained, shed light on the molecular basis underlying the structure and function of the junction between the epidermis and dermis, including the pivotal role that type VII collagen plays in the normal adhesion of these two layers. Researchers then learned that, in EB, the family of genetic diseases characterized by skin fragility, “dystrophic types are caused by mutations in the gene encoding type VII collagen,” he said.

“Just as the advent of monoclonal antibodies allowed us to start attacking psoriasis and atopic dermatitis in unprecedented ways, the advent of gene therapy allows us to potentially address the fundamental molecular genetic defect of various types of EB,” Dr. Ju said.

While gene therapy is “still in its infancy,” companies have begun using the tools to address EB. One gene therapy in the pipeline – in phase 3 clinical trial testing – involves grafting back into patients with recessive dystrophic EB their skin cells that have been genetically modified to produce a correct (nonmutated) type VII collagen, he said.

Basal cell nevus syndrome, or Gorlin syndrome, a rare disease in which patients develop a multitude of basal cell carcinoma tumors, is another example of a “dermatology first” approach, Dr. Ju said. Research identified a genetic mutation that causes the hedgehog signaling pathway to be inappropriately activated in the disease, and a drug, vismodegib, was developed to inhibit this pathway. The drug was initially approved for patients with metastatic basal cell cancer and types of advanced basal cell cancer, and is now being tested in cancers affecting other organs, he said.

Basal cell cancer “is a huge market, but it was really unrecognized in the past,” Dr. Eaglstein said. “Seeing drugs come to market for basal cell cancer – this wouldn’t have happened [decades ago].”

Dr. Ju has worked in the pharmaceutical industry; all other sources in this story have worked with pharmaceutical manufacturers of treatments that are being developed or have been approved to treat dermatologic diseases mentioned in this story. In addition to Dr. Ju, Dr. Eaglstein and Dr. Orlow are cofounders of the Advancing Innovation in Dermatology group; Dr. Orlow is a member of the program committee for the organization’s dermatology summit conference.

 

A dive into the dermatology data pool reveals a great deal of change in the 50 years that Dermatology News and Skin & Allergy News have been covering the specialty.

For one thing, there are a lot more dermatologists now. In 1970, there were 4,004 dermatologists in the United States, according to the American Medical Association, and as of 2019, the total was up to 19,957. The American Academy of Dermatology puts its 2020 membership at a somewhat lower 18,898, noting that not all dermatologists are AAD members.

Much of that 50-year increase comes from the larger proportion of women entering the specialty. In 1970, only 7% of dermatologists were women, but by 2019 they represented over 37% of the dermatology workforce, according to the AMA numbers. The AAD, however, reports more women than the AMA (8,940 vs. 7,482), so the proportion of female academy members in 2020 is about 47%.

The population of dermatologists has increased faster than the general population since 1970, leading to a rising density of providers. A report from 1973 put the national figure at 1.7 dermatologists per 100,000 population in 1970, and two more recent studies in JAMA Dermatology reported density levels of 3.65 per 100,000 in 2013 and 3.36 per 100,000 in 2016.

In that 1973 report, the authors said that there was “no evidence to suggest that there will not be sufficient dermatologists in the future, if training centers are maintained and adequately financed,” noting that “the current rate of filling of dermatologic residency positions should not diminish and may continue to increase.”

In 2017, the conclusion was quite different: “Dermatologists alone have been unable to meet increasing patient demand for dermatologic services. The number of dermatology residency training positions has been relatively stagnant, suggesting that the current supply of dermatologists in training will be insufficient to fully meet growing future demand.”

The current state of strong demand for dermatologists does come with some benefits. In a 2019 survey by physician recruitment firm Merritt Hawkins, dermatologists had the 6th-highest starting salary at $420,000 a year. An article in the July 1971 issue of Skin & Allergy News offered a somewhat different perspective on compensation for first-year dermatologists: Recommendations offered by those already in practice ranged from $12,000 to $24,000.

Those first-year physicians are coming from residencies that, not too surprisingly, are now producing more new dermatologists than they did in 1970, although perhaps not as many more as might be expected.

There were an estimated 250 individuals completing dermatology residencies annually in 1976 (J Am Acad Dermatol. 1981;4[3]:344-5), which suggests a total of approximately 750 active residents at a time when there were about 5,000 practicing dermatologists in the country.

For the 2018-2019 academic year, there were 1,439 active residents in U.S. training programs, according to the Association of American Medical Colleges, so there were twice the number of residents but four times as many dermatologists in practice, compared with 1976.

The next link in the dermatology supply chain would be the medical schools, and there the numbers of full-time faculty have more than kept up. For the 1969-1970 academic year, there were 202 full-time positions in dermatology (JAMA. 1970;214:1483-581). By 2019, the number had risen to 1,519, according to the Association of American Medical Colleges.

[email protected]

A dive into the dermatology data pool reveals a great deal of change in the 50 years that Dermatology News and Skin & Allergy News have been covering the specialty.

For one thing, there are a lot more dermatologists now. In 1970, there were 4,004 dermatologists in the United States, according to the American Medical Association, and as of 2019, the total was up to 19,957. The American Academy of Dermatology puts its 2020 membership at a somewhat lower 18,898, noting that not all dermatologists are AAD members.

Much of that 50-year increase comes from the larger proportion of women entering the specialty. In 1970, only 7% of dermatologists were women, but by 2019 they represented over 37% of the dermatology workforce, according to the AMA numbers. The AAD, however, reports more women than the AMA (8,940 vs. 7,482), so the proportion of female academy members in 2020 is about 47%.

The population of dermatologists has increased faster than the general population since 1970, leading to a rising density of providers. A report from 1973 put the national figure at 1.7 dermatologists per 100,000 population in 1970, and two more recent studies in JAMA Dermatology reported density levels of 3.65 per 100,000 in 2013 and 3.36 per 100,000 in 2016.

In that 1973 report, the authors said that there was “no evidence to suggest that there will not be sufficient dermatologists in the future, if training centers are maintained and adequately financed,” noting that “the current rate of filling of dermatologic residency positions should not diminish and may continue to increase.”

In 2017, the conclusion was quite different: “Dermatologists alone have been unable to meet increasing patient demand for dermatologic services. The number of dermatology residency training positions has been relatively stagnant, suggesting that the current supply of dermatologists in training will be insufficient to fully meet growing future demand.”

The current state of strong demand for dermatologists does come with some benefits. In a 2019 survey by physician recruitment firm Merritt Hawkins, dermatologists had the 6th-highest starting salary at $420,000 a year. An article in the July 1971 issue of Skin & Allergy News offered a somewhat different perspective on compensation for first-year dermatologists: Recommendations offered by those already in practice ranged from $12,000 to $24,000.

Those first-year physicians are coming from residencies that, not too surprisingly, are now producing more new dermatologists than they did in 1970, although perhaps not as many more as might be expected.

There were an estimated 250 individuals completing dermatology residencies annually in 1976 (J Am Acad Dermatol. 1981;4[3]:344-5), which suggests a total of approximately 750 active residents at a time when there were about 5,000 practicing dermatologists in the country.

For the 2018-2019 academic year, there were 1,439 active residents in U.S. training programs, according to the Association of American Medical Colleges, so there were twice the number of residents but four times as many dermatologists in practice, compared with 1976.

The next link in the dermatology supply chain would be the medical schools, and there the numbers of full-time faculty have more than kept up. For the 1969-1970 academic year, there were 202 full-time positions in dermatology (JAMA. 1970;214:1483-581). By 2019, the number had risen to 1,519, according to the Association of American Medical Colleges.

[email protected]

A dive into the dermatology data pool reveals a great deal of change in the 50 years that Dermatology News and Skin & Allergy News have been covering the specialty.

For one thing, there are a lot more dermatologists now. In 1970, there were 4,004 dermatologists in the United States, according to the American Medical Association, and as of 2019, the total was up to 19,957. The American Academy of Dermatology puts its 2020 membership at a somewhat lower 18,898, noting that not all dermatologists are AAD members.

Much of that 50-year increase comes from the larger proportion of women entering the specialty. In 1970, only 7% of dermatologists were women, but by 2019 they represented over 37% of the dermatology workforce, according to the AMA numbers. The AAD, however, reports more women than the AMA (8,940 vs. 7,482), so the proportion of female academy members in 2020 is about 47%.

The population of dermatologists has increased faster than the general population since 1970, leading to a rising density of providers. A report from 1973 put the national figure at 1.7 dermatologists per 100,000 population in 1970, and two more recent studies in JAMA Dermatology reported density levels of 3.65 per 100,000 in 2013 and 3.36 per 100,000 in 2016.

In that 1973 report, the authors said that there was “no evidence to suggest that there will not be sufficient dermatologists in the future, if training centers are maintained and adequately financed,” noting that “the current rate of filling of dermatologic residency positions should not diminish and may continue to increase.”

In 2017, the conclusion was quite different: “Dermatologists alone have been unable to meet increasing patient demand for dermatologic services. The number of dermatology residency training positions has been relatively stagnant, suggesting that the current supply of dermatologists in training will be insufficient to fully meet growing future demand.”

The current state of strong demand for dermatologists does come with some benefits. In a 2019 survey by physician recruitment firm Merritt Hawkins, dermatologists had the 6th-highest starting salary at $420,000 a year. An article in the July 1971 issue of Skin & Allergy News offered a somewhat different perspective on compensation for first-year dermatologists: Recommendations offered by those already in practice ranged from $12,000 to $24,000.

Those first-year physicians are coming from residencies that, not too surprisingly, are now producing more new dermatologists than they did in 1970, although perhaps not as many more as might be expected.

There were an estimated 250 individuals completing dermatology residencies annually in 1976 (J Am Acad Dermatol. 1981;4[3]:344-5), which suggests a total of approximately 750 active residents at a time when there were about 5,000 practicing dermatologists in the country.

For the 2018-2019 academic year, there were 1,439 active residents in U.S. training programs, according to the Association of American Medical Colleges, so there were twice the number of residents but four times as many dermatologists in practice, compared with 1976.

The next link in the dermatology supply chain would be the medical schools, and there the numbers of full-time faculty have more than kept up. For the 1969-1970 academic year, there were 202 full-time positions in dermatology (JAMA. 1970;214:1483-581). By 2019, the number had risen to 1,519, according to the Association of American Medical Colleges.

[email protected]

Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.

Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.

“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.

“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”

Much of the progress in psoriasis treatment in the past 50 years unfolded over the past 2 decades, with biologics emerging for psoriasis, said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.

There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.

In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”

In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.

“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.

Enter the biologics era

The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.

Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.

Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.

“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”

It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.

“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”

Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.

Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.

Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.

Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.

Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.

“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.

Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.

He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.

It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”

“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.

That research is underway, and the future looks bright – and clear.
 

“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”

In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”

All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.

[email protected]
 

Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.

Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.

“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.

“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”

Much of the progress in psoriasis treatment in the past 50 years unfolded over the past 2 decades, with biologics emerging for psoriasis, said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.

There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.

In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”

In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.

“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.

Enter the biologics era

The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.

Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.

Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.

“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”

It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.

“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”

Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.

Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.

Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.

Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.

Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.

“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.

Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.

He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.

It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”

“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.

That research is underway, and the future looks bright – and clear.
 

“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”

In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”

All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.

[email protected]
 

Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.

Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.

“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.

“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”

Much of the progress in psoriasis treatment in the past 50 years unfolded over the past 2 decades, with biologics emerging for psoriasis, said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.

There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.

In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”

In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.

“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.

Enter the biologics era

The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.

Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.

Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.

“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”

It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.

“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”

Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.

Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.

Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.

Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.

Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.

“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.

Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.

He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.

It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”

“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.

That research is underway, and the future looks bright – and clear.
 

“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”

In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”

All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.

[email protected]
 

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

As Dermatology News (formerly Skin and Allergy News) reaches its 50th-year milestone, a reflection on the history of the discipline, especially in the United States, up to the time of the launch of this publication is in order. Such an overview must, of course, be cursory in this context. Yet, for those who want to learn more, a large body of historical references and research has been created to fill in the gaps, as modern dermatology has always been cognizant of the importance of its history, with many individuals and groups drawn to the subject.

National Library of Medicien/Public Domain

Two excellent sources for the history of the field can be found in work by William Allen Pusey, MD (1865-1940), and Herbert Rattner, MD (1900-1962), “The History of Dermatology” published in 1933 and research by members of the History of Dermatology Society, founded in 1973 in New York.

Modern dermatology

The development of the field of modern dermatology can be traced back to the early to mid-19th century. During the first half of the 19th century, England and France dominated the study of dermatology, but by the middle of the century, the German revolution in microparasitology shifted that focus “with remarkable German discoveries,” according to Bernard S. Potter, MD, in his review of bibliographic landmarks of the history of dermatology (J Am Acad Dermatol 2003;48:919-32). For example, Johann Lucas Schoenlein (1793-1864) in 1839 discovered the fungal origin of favus, and in 1841 Jacob Henle (1809-1885) discovered Demodex folliculorum. Karl Ferdinand Eichstedt (1816-1892) in 1846 followed with the discovery of the causative agent of pityriasis versicolor, and Friedrich Wilhelm Felix von Barensprung (1822-1864) in 1862 coined the term erythrasma and named the organism responsible for this condition Microsporum minutissimum.

Dr. Potter described how American dermatology originated in New York City in 1836 when Henry Daggett Bulkley, MD, (1803-1872) opened the first dispensary for skin diseases, the Broome Street Infirmary for Diseases of the Skin, thus creating the first institution in the United States for the treatment of cutaneous disease. As the first American dermatologist, he was also the first in the United States to lecture on and to exclusively practice dermatology.

The rise of interest in the importance of dermatology led to the organization of the early American Dermatological Association in 1886.

However, the state of dermatology as a science in the 19th century was not always looked upon favorably, even by its practitioners, especially in the United States. In 1871, in a “Review on Modern Dermatology,” given as a series of lectures on skin disease at Harvard University, James C. White, MD (1833-1916) of Massachusetts General Hospital, stated that: “Were the literature of skin diseases previous to that of the last half-century absolutely annihilated, and with it, the influence it has exercised upon that of the present day, it would be an immense gain to dermatology, although much of real value would perish.” He lamented that America had contributed little so far to the study of dermatology, and that the discipline was only taught in some of its largest schools, and he urged that this be changed. He also lamented that The American Journal of Syphilography and Dermatology, established the year before, had so far proved itself heavy on syphilis, but light on dermatology, a situation he also hoped would change dramatically.

By the late-19th century, the conviction that diseases of the skin needed to be connected to the overall metabolism and physiology of the patient as a whole was becoming more mainstream.

“It has been, and still is, too much the custom to study diseases of the skin in the light of pathological pictures, to name the local manifestation and to so label it as disease. It is much easier to give the disease name and to label it than it is to comprehend the process at work. The former is comparatively unimportant for the patient, the latter point upon which recovery may depend. The nature and meaning of the process in connection with the cutaneous symptoms has not received enough attention, and I believe this to be one reason why the treatment of many of these diseases in the past has been so notoriously unsatisfactory,” Louis A. Duhring, MD (1845-1913) chided his colleagues in the Section of Dermatology and Syphilography, at the Forty-fourth Annual Meeting of the American Medical Association in 1894. (collections.nlm.nih.gov/ext/dw/101489447/PDF/101489447.pdf)

In the early-20th century, German dermatology influenced American dermatology more than any other, according to Karl Holubar, MD, of the Institute for the History of Medicine, University of Vienna, in his lecture on the history of European dermatopathology.

He stated that, with regard to dermatopathology, it was Oscar Gans, MD (1888-1983) who brought the latest knowledge into the United States by delivering a series of lectures at Mayo Clinic in the late 1920s upon the invitation of Paul A. O’Leary, MD, (1891-1955) who then headed the Mayo section of dermatology.

By the 1930s, a flurry of organizational activity overtook American dermatology. In 1932, the American Board of Dermatology was established, with its first exams given in 1933 (20 students passed, 7 failed). The Society for Investigative Dermatology was founded in 1937, and the American Academy of Dermatology and Syphilology (now the American Academy of Dermatology), founded in 1938.

The 1930s also saw a major influx of German and other European Jews fleeing Nazi oppression who would forever change the face of American dermatology. “Between 1933 and 1938, a series of repressive measures eliminated them from the practice of medicine in Germany and other countries. Although some died in concentration camps and others committed suicide, many were able to emigrate from Europe. Dermatology in the United States particularly benefited from the influx of several stellar Jewish dermatologists who were major contributors to the subsequent flowering of academic dermatology in the United States” (JAMA Derm. 2013;149[9]:1090-4).

“The overtures of the holocaust and the rising power of Hitler in Europe finally brought over to the United States the flower of dermatologists and investigators of the German School, e.g., Alexander and Walter Lever, Felix and Hermann Pinkus, the Epsteins, Erich Auerbach, Stephen Rothman, to name just a few. With this exodus and transfer of brain power, Europe lost its leading role to never again regain it,” according to Dr. Holubar. Walter F. Lever, MD (1909-1992) was especially well-known for his landmark textbook on dermatology, “Histopathology of the Skin,” published in the United States in 1949.

The therapeutic era

Throughout the 19th century, a variety of soaps and patent medicines were touted as cure-alls for a host of skin diseases. Other than their benefits to surface cleanliness and their antiseptic properties, however, they were of little effect.

It wasn’t until the 20th century that truly effective therapeutics entered the dermatologic pharmacopoeia. In their 1989 review, Diane Quintal, MD, and Robert Jackson, MD, discussed the origins of the most important of these drugs and pointed out that, “Until this century, the essence of dermatology resided in the realm of morphology. Early contributors largely confined their activities to the classification of skin diseases and to the elaboration of clinical dermatologic entities based on morphologic features. ... but “in the last 50 years, there have been significant scientific discoveries in the field of therapeutics that have revolutionized the practice of dermatology.“ (Clin Dermatol. 1989;7[3]38-47).

These key drugs comprised:

• Quinacrine was introduced in 1932 by Walter Kikuth, MD, as an antimalarial drug. But it was not until 1940, that A.J. Prokoptchouksi, MD, reported on its effectiveness 35 patients with lupus erythematosus.
• Para-aminobenzoic acid (PABA) came into prominence in 1942, when Stephen Rothman, MD, and Jack Rubin, MD, at the University of Chicago, published the results of their experiment, showing that when PABA was incorporated in an ointment base and applied to the skin, it could protect against sunburn.
• Dapsone. The effectiveness of sulfapyridine was demonstrated in 1947 by M.J. Costello, MD, who reported its usefulness in a patient with dermatitis herpetiformis, which he believed to be caused by a bacterial allergy. Sulfapyridine controlled the disease, but gastrointestinal intolerance and sulfonamide sensitivity were side effects. Ultimately, in 1951, Theodore Cornbleet, MD, introduced the use of sulfoxones in his article entitled “Sulfoxone (diasones) sodium for dermatitis herpetiformis,” considered more effective than sulfapyridine. Dapsone is the active principal ingredient.
• Hydrocortisone. In August 1952, Marion Sulzberger, MD, and Victor H. Witten, MD (both members of the first Skin & Allergy News editorial advisory board), described use of Compound F (17-hydroxycorticosterone-21-acetate, hydrocortisone) in seven cases of atopic dermatitis and one case of discoid or subacute lupus erythematosus, reporting improvement in all of these cases.
• Benzoyl peroxide. Canadian dermatologist William E. Pace, MD, reported on the beneficial effects of benzoyl peroxide on acne in 1953. The product had originally been used for chronic Staphylococcus aureus folliculitis of the beard.
• Griseofulvin, a metabolic byproduct of a number of species of Penicillium, was first isolated in 1939. But in 1958, Harvey Blank, MD, at the University of Miami (also on the first Skin & Allergy News editorial advisory board), and Stanley I. Cullen, MD, administered the drug to a patient with Trichophyton rubrum granuloma, in the first human trial. In 1959, they reported the drug’s benefits on 31 patients with various fungal infections.
• Methotrexate. In 1951, R. Gubner, MD, and colleagues noticed the rapid clearing of skin lesions in a patient with rheumatoid arthritis who had been treated with the folic acid antagonist, aminopterin. And in 1958, W.F. Edmundson, MD, and W.B. Guy, MD, reported on the oral use of the folic acid antagonist, methotrexate. This was followed by multiple reports on the successful use of methotrexate in psoriasis.
• 5-fluorouracil (5-FU). In 1957, 5-FU, an antimetabolite of uracil, was first synthesized. In 1962, G. Falkson, MD, and E.J. Schulz, MD, reported on skin changes observed in 85 patients being treated with systemic 5-FU for advanced carcinomatosis. They found that 31 of the 85 patients developed sensitivity to sunlight and subsequent disappearance of actinic keratoses in these same patients.

Technology in skin care also was developing in the era just before the launch of Skin & Allergy News. For example, Leon Goldman, MD, then chairman of the department of dermatology at the University of Cincinnati, was the first physician to use a laser for tattoo removal. His publication in 1965 helped to solidify its use, leading him to be “regarded by many in the dermatologic community as the ‘godfather of lasers in medicine and surgery’ ” (Clin Dermatol. 2007;25:434-42).

So, by 1970, dermatology as a field had established itself fully with a strong societal infrastructure, a vibrant base of journals and books, and an evolving set of scientific and technical tools. The launch of Skin & Allergy News (now Dermatology News) that year would chronicle dermatology’s commitment to the development of new therapeutics and technologies in service of patient needs – the stories of which would grace the newspaper’s pages for 5 decades and counting.

[email protected]

As Dermatology News (formerly Skin and Allergy News) reaches its 50th-year milestone, a reflection on the history of the discipline, especially in the United States, up to the time of the launch of this publication is in order. Such an overview must, of course, be cursory in this context. Yet, for those who want to learn more, a large body of historical references and research has been created to fill in the gaps, as modern dermatology has always been cognizant of the importance of its history, with many individuals and groups drawn to the subject.

National Library of Medicien/Public Domain

Two excellent sources for the history of the field can be found in work by William Allen Pusey, MD (1865-1940), and Herbert Rattner, MD (1900-1962), “The History of Dermatology” published in 1933 and research by members of the History of Dermatology Society, founded in 1973 in New York.

Modern dermatology

The development of the field of modern dermatology can be traced back to the early to mid-19th century. During the first half of the 19th century, England and France dominated the study of dermatology, but by the middle of the century, the German revolution in microparasitology shifted that focus “with remarkable German discoveries,” according to Bernard S. Potter, MD, in his review of bibliographic landmarks of the history of dermatology (J Am Acad Dermatol 2003;48:919-32). For example, Johann Lucas Schoenlein (1793-1864) in 1839 discovered the fungal origin of favus, and in 1841 Jacob Henle (1809-1885) discovered Demodex folliculorum. Karl Ferdinand Eichstedt (1816-1892) in 1846 followed with the discovery of the causative agent of pityriasis versicolor, and Friedrich Wilhelm Felix von Barensprung (1822-1864) in 1862 coined the term erythrasma and named the organism responsible for this condition Microsporum minutissimum.

Dr. Potter described how American dermatology originated in New York City in 1836 when Henry Daggett Bulkley, MD, (1803-1872) opened the first dispensary for skin diseases, the Broome Street Infirmary for Diseases of the Skin, thus creating the first institution in the United States for the treatment of cutaneous disease. As the first American dermatologist, he was also the first in the United States to lecture on and to exclusively practice dermatology.

The rise of interest in the importance of dermatology led to the organization of the early American Dermatological Association in 1886.

However, the state of dermatology as a science in the 19th century was not always looked upon favorably, even by its practitioners, especially in the United States. In 1871, in a “Review on Modern Dermatology,” given as a series of lectures on skin disease at Harvard University, James C. White, MD (1833-1916) of Massachusetts General Hospital, stated that: “Were the literature of skin diseases previous to that of the last half-century absolutely annihilated, and with it, the influence it has exercised upon that of the present day, it would be an immense gain to dermatology, although much of real value would perish.” He lamented that America had contributed little so far to the study of dermatology, and that the discipline was only taught in some of its largest schools, and he urged that this be changed. He also lamented that The American Journal of Syphilography and Dermatology, established the year before, had so far proved itself heavy on syphilis, but light on dermatology, a situation he also hoped would change dramatically.

By the late-19th century, the conviction that diseases of the skin needed to be connected to the overall metabolism and physiology of the patient as a whole was becoming more mainstream.

“It has been, and still is, too much the custom to study diseases of the skin in the light of pathological pictures, to name the local manifestation and to so label it as disease. It is much easier to give the disease name and to label it than it is to comprehend the process at work. The former is comparatively unimportant for the patient, the latter point upon which recovery may depend. The nature and meaning of the process in connection with the cutaneous symptoms has not received enough attention, and I believe this to be one reason why the treatment of many of these diseases in the past has been so notoriously unsatisfactory,” Louis A. Duhring, MD (1845-1913) chided his colleagues in the Section of Dermatology and Syphilography, at the Forty-fourth Annual Meeting of the American Medical Association in 1894. (collections.nlm.nih.gov/ext/dw/101489447/PDF/101489447.pdf)

In the early-20th century, German dermatology influenced American dermatology more than any other, according to Karl Holubar, MD, of the Institute for the History of Medicine, University of Vienna, in his lecture on the history of European dermatopathology.

He stated that, with regard to dermatopathology, it was Oscar Gans, MD (1888-1983) who brought the latest knowledge into the United States by delivering a series of lectures at Mayo Clinic in the late 1920s upon the invitation of Paul A. O’Leary, MD, (1891-1955) who then headed the Mayo section of dermatology.

By the 1930s, a flurry of organizational activity overtook American dermatology. In 1932, the American Board of Dermatology was established, with its first exams given in 1933 (20 students passed, 7 failed). The Society for Investigative Dermatology was founded in 1937, and the American Academy of Dermatology and Syphilology (now the American Academy of Dermatology), founded in 1938.

The 1930s also saw a major influx of German and other European Jews fleeing Nazi oppression who would forever change the face of American dermatology. “Between 1933 and 1938, a series of repressive measures eliminated them from the practice of medicine in Germany and other countries. Although some died in concentration camps and others committed suicide, many were able to emigrate from Europe. Dermatology in the United States particularly benefited from the influx of several stellar Jewish dermatologists who were major contributors to the subsequent flowering of academic dermatology in the United States” (JAMA Derm. 2013;149[9]:1090-4).

“The overtures of the holocaust and the rising power of Hitler in Europe finally brought over to the United States the flower of dermatologists and investigators of the German School, e.g., Alexander and Walter Lever, Felix and Hermann Pinkus, the Epsteins, Erich Auerbach, Stephen Rothman, to name just a few. With this exodus and transfer of brain power, Europe lost its leading role to never again regain it,” according to Dr. Holubar. Walter F. Lever, MD (1909-1992) was especially well-known for his landmark textbook on dermatology, “Histopathology of the Skin,” published in the United States in 1949.

The therapeutic era

Throughout the 19th century, a variety of soaps and patent medicines were touted as cure-alls for a host of skin diseases. Other than their benefits to surface cleanliness and their antiseptic properties, however, they were of little effect.

It wasn’t until the 20th century that truly effective therapeutics entered the dermatologic pharmacopoeia. In their 1989 review, Diane Quintal, MD, and Robert Jackson, MD, discussed the origins of the most important of these drugs and pointed out that, “Until this century, the essence of dermatology resided in the realm of morphology. Early contributors largely confined their activities to the classification of skin diseases and to the elaboration of clinical dermatologic entities based on morphologic features. ... but “in the last 50 years, there have been significant scientific discoveries in the field of therapeutics that have revolutionized the practice of dermatology.“ (Clin Dermatol. 1989;7[3]38-47).

These key drugs comprised:

• Quinacrine was introduced in 1932 by Walter Kikuth, MD, as an antimalarial drug. But it was not until 1940, that A.J. Prokoptchouksi, MD, reported on its effectiveness 35 patients with lupus erythematosus.
• Para-aminobenzoic acid (PABA) came into prominence in 1942, when Stephen Rothman, MD, and Jack Rubin, MD, at the University of Chicago, published the results of their experiment, showing that when PABA was incorporated in an ointment base and applied to the skin, it could protect against sunburn.
• Dapsone. The effectiveness of sulfapyridine was demonstrated in 1947 by M.J. Costello, MD, who reported its usefulness in a patient with dermatitis herpetiformis, which he believed to be caused by a bacterial allergy. Sulfapyridine controlled the disease, but gastrointestinal intolerance and sulfonamide sensitivity were side effects. Ultimately, in 1951, Theodore Cornbleet, MD, introduced the use of sulfoxones in his article entitled “Sulfoxone (diasones) sodium for dermatitis herpetiformis,” considered more effective than sulfapyridine. Dapsone is the active principal ingredient.
• Hydrocortisone. In August 1952, Marion Sulzberger, MD, and Victor H. Witten, MD (both members of the first Skin & Allergy News editorial advisory board), described use of Compound F (17-hydroxycorticosterone-21-acetate, hydrocortisone) in seven cases of atopic dermatitis and one case of discoid or subacute lupus erythematosus, reporting improvement in all of these cases.
• Benzoyl peroxide. Canadian dermatologist William E. Pace, MD, reported on the beneficial effects of benzoyl peroxide on acne in 1953. The product had originally been used for chronic Staphylococcus aureus folliculitis of the beard.
• Griseofulvin, a metabolic byproduct of a number of species of Penicillium, was first isolated in 1939. But in 1958, Harvey Blank, MD, at the University of Miami (also on the first Skin & Allergy News editorial advisory board), and Stanley I. Cullen, MD, administered the drug to a patient with Trichophyton rubrum granuloma, in the first human trial. In 1959, they reported the drug’s benefits on 31 patients with various fungal infections.
• Methotrexate. In 1951, R. Gubner, MD, and colleagues noticed the rapid clearing of skin lesions in a patient with rheumatoid arthritis who had been treated with the folic acid antagonist, aminopterin. And in 1958, W.F. Edmundson, MD, and W.B. Guy, MD, reported on the oral use of the folic acid antagonist, methotrexate. This was followed by multiple reports on the successful use of methotrexate in psoriasis.
• 5-fluorouracil (5-FU). In 1957, 5-FU, an antimetabolite of uracil, was first synthesized. In 1962, G. Falkson, MD, and E.J. Schulz, MD, reported on skin changes observed in 85 patients being treated with systemic 5-FU for advanced carcinomatosis. They found that 31 of the 85 patients developed sensitivity to sunlight and subsequent disappearance of actinic keratoses in these same patients.

Technology in skin care also was developing in the era just before the launch of Skin & Allergy News. For example, Leon Goldman, MD, then chairman of the department of dermatology at the University of Cincinnati, was the first physician to use a laser for tattoo removal. His publication in 1965 helped to solidify its use, leading him to be “regarded by many in the dermatologic community as the ‘godfather of lasers in medicine and surgery’ ” (Clin Dermatol. 2007;25:434-42).

So, by 1970, dermatology as a field had established itself fully with a strong societal infrastructure, a vibrant base of journals and books, and an evolving set of scientific and technical tools. The launch of Skin & Allergy News (now Dermatology News) that year would chronicle dermatology’s commitment to the development of new therapeutics and technologies in service of patient needs – the stories of which would grace the newspaper’s pages for 5 decades and counting.

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As Dermatology News (formerly Skin and Allergy News) reaches its 50th-year milestone, a reflection on the history of the discipline, especially in the United States, up to the time of the launch of this publication is in order. Such an overview must, of course, be cursory in this context. Yet, for those who want to learn more, a large body of historical references and research has been created to fill in the gaps, as modern dermatology has always been cognizant of the importance of its history, with many individuals and groups drawn to the subject.

National Library of Medicien/Public Domain

Two excellent sources for the history of the field can be found in work by William Allen Pusey, MD (1865-1940), and Herbert Rattner, MD (1900-1962), “The History of Dermatology” published in 1933 and research by members of the History of Dermatology Society, founded in 1973 in New York.

Modern dermatology

The development of the field of modern dermatology can be traced back to the early to mid-19th century. During the first half of the 19th century, England and France dominated the study of dermatology, but by the middle of the century, the German revolution in microparasitology shifted that focus “with remarkable German discoveries,” according to Bernard S. Potter, MD, in his review of bibliographic landmarks of the history of dermatology (J Am Acad Dermatol 2003;48:919-32). For example, Johann Lucas Schoenlein (1793-1864) in 1839 discovered the fungal origin of favus, and in 1841 Jacob Henle (1809-1885) discovered Demodex folliculorum. Karl Ferdinand Eichstedt (1816-1892) in 1846 followed with the discovery of the causative agent of pityriasis versicolor, and Friedrich Wilhelm Felix von Barensprung (1822-1864) in 1862 coined the term erythrasma and named the organism responsible for this condition Microsporum minutissimum.

Dr. Potter described how American dermatology originated in New York City in 1836 when Henry Daggett Bulkley, MD, (1803-1872) opened the first dispensary for skin diseases, the Broome Street Infirmary for Diseases of the Skin, thus creating the first institution in the United States for the treatment of cutaneous disease. As the first American dermatologist, he was also the first in the United States to lecture on and to exclusively practice dermatology.

The rise of interest in the importance of dermatology led to the organization of the early American Dermatological Association in 1886.

However, the state of dermatology as a science in the 19th century was not always looked upon favorably, even by its practitioners, especially in the United States. In 1871, in a “Review on Modern Dermatology,” given as a series of lectures on skin disease at Harvard University, James C. White, MD (1833-1916) of Massachusetts General Hospital, stated that: “Were the literature of skin diseases previous to that of the last half-century absolutely annihilated, and with it, the influence it has exercised upon that of the present day, it would be an immense gain to dermatology, although much of real value would perish.” He lamented that America had contributed little so far to the study of dermatology, and that the discipline was only taught in some of its largest schools, and he urged that this be changed. He also lamented that The American Journal of Syphilography and Dermatology, established the year before, had so far proved itself heavy on syphilis, but light on dermatology, a situation he also hoped would change dramatically.

By the late-19th century, the conviction that diseases of the skin needed to be connected to the overall metabolism and physiology of the patient as a whole was becoming more mainstream.

“It has been, and still is, too much the custom to study diseases of the skin in the light of pathological pictures, to name the local manifestation and to so label it as disease. It is much easier to give the disease name and to label it than it is to comprehend the process at work. The former is comparatively unimportant for the patient, the latter point upon which recovery may depend. The nature and meaning of the process in connection with the cutaneous symptoms has not received enough attention, and I believe this to be one reason why the treatment of many of these diseases in the past has been so notoriously unsatisfactory,” Louis A. Duhring, MD (1845-1913) chided his colleagues in the Section of Dermatology and Syphilography, at the Forty-fourth Annual Meeting of the American Medical Association in 1894. (collections.nlm.nih.gov/ext/dw/101489447/PDF/101489447.pdf)

In the early-20th century, German dermatology influenced American dermatology more than any other, according to Karl Holubar, MD, of the Institute for the History of Medicine, University of Vienna, in his lecture on the history of European dermatopathology.

He stated that, with regard to dermatopathology, it was Oscar Gans, MD (1888-1983) who brought the latest knowledge into the United States by delivering a series of lectures at Mayo Clinic in the late 1920s upon the invitation of Paul A. O’Leary, MD, (1891-1955) who then headed the Mayo section of dermatology.

By the 1930s, a flurry of organizational activity overtook American dermatology. In 1932, the American Board of Dermatology was established, with its first exams given in 1933 (20 students passed, 7 failed). The Society for Investigative Dermatology was founded in 1937, and the American Academy of Dermatology and Syphilology (now the American Academy of Dermatology), founded in 1938.

The 1930s also saw a major influx of German and other European Jews fleeing Nazi oppression who would forever change the face of American dermatology. “Between 1933 and 1938, a series of repressive measures eliminated them from the practice of medicine in Germany and other countries. Although some died in concentration camps and others committed suicide, many were able to emigrate from Europe. Dermatology in the United States particularly benefited from the influx of several stellar Jewish dermatologists who were major contributors to the subsequent flowering of academic dermatology in the United States” (JAMA Derm. 2013;149[9]:1090-4).

“The overtures of the holocaust and the rising power of Hitler in Europe finally brought over to the United States the flower of dermatologists and investigators of the German School, e.g., Alexander and Walter Lever, Felix and Hermann Pinkus, the Epsteins, Erich Auerbach, Stephen Rothman, to name just a few. With this exodus and transfer of brain power, Europe lost its leading role to never again regain it,” according to Dr. Holubar. Walter F. Lever, MD (1909-1992) was especially well-known for his landmark textbook on dermatology, “Histopathology of the Skin,” published in the United States in 1949.

The therapeutic era

Throughout the 19th century, a variety of soaps and patent medicines were touted as cure-alls for a host of skin diseases. Other than their benefits to surface cleanliness and their antiseptic properties, however, they were of little effect.

It wasn’t until the 20th century that truly effective therapeutics entered the dermatologic pharmacopoeia. In their 1989 review, Diane Quintal, MD, and Robert Jackson, MD, discussed the origins of the most important of these drugs and pointed out that, “Until this century, the essence of dermatology resided in the realm of morphology. Early contributors largely confined their activities to the classification of skin diseases and to the elaboration of clinical dermatologic entities based on morphologic features. ... but “in the last 50 years, there have been significant scientific discoveries in the field of therapeutics that have revolutionized the practice of dermatology.“ (Clin Dermatol. 1989;7[3]38-47).

These key drugs comprised:

• Quinacrine was introduced in 1932 by Walter Kikuth, MD, as an antimalarial drug. But it was not until 1940, that A.J. Prokoptchouksi, MD, reported on its effectiveness 35 patients with lupus erythematosus.
• Para-aminobenzoic acid (PABA) came into prominence in 1942, when Stephen Rothman, MD, and Jack Rubin, MD, at the University of Chicago, published the results of their experiment, showing that when PABA was incorporated in an ointment base and applied to the skin, it could protect against sunburn.
• Dapsone. The effectiveness of sulfapyridine was demonstrated in 1947 by M.J. Costello, MD, who reported its usefulness in a patient with dermatitis herpetiformis, which he believed to be caused by a bacterial allergy. Sulfapyridine controlled the disease, but gastrointestinal intolerance and sulfonamide sensitivity were side effects. Ultimately, in 1951, Theodore Cornbleet, MD, introduced the use of sulfoxones in his article entitled “Sulfoxone (diasones) sodium for dermatitis herpetiformis,” considered more effective than sulfapyridine. Dapsone is the active principal ingredient.
• Hydrocortisone. In August 1952, Marion Sulzberger, MD, and Victor H. Witten, MD (both members of the first Skin & Allergy News editorial advisory board), described use of Compound F (17-hydroxycorticosterone-21-acetate, hydrocortisone) in seven cases of atopic dermatitis and one case of discoid or subacute lupus erythematosus, reporting improvement in all of these cases.
• Benzoyl peroxide. Canadian dermatologist William E. Pace, MD, reported on the beneficial effects of benzoyl peroxide on acne in 1953. The product had originally been used for chronic Staphylococcus aureus folliculitis of the beard.
• Griseofulvin, a metabolic byproduct of a number of species of Penicillium, was first isolated in 1939. But in 1958, Harvey Blank, MD, at the University of Miami (also on the first Skin & Allergy News editorial advisory board), and Stanley I. Cullen, MD, administered the drug to a patient with Trichophyton rubrum granuloma, in the first human trial. In 1959, they reported the drug’s benefits on 31 patients with various fungal infections.
• Methotrexate. In 1951, R. Gubner, MD, and colleagues noticed the rapid clearing of skin lesions in a patient with rheumatoid arthritis who had been treated with the folic acid antagonist, aminopterin. And in 1958, W.F. Edmundson, MD, and W.B. Guy, MD, reported on the oral use of the folic acid antagonist, methotrexate. This was followed by multiple reports on the successful use of methotrexate in psoriasis.
• 5-fluorouracil (5-FU). In 1957, 5-FU, an antimetabolite of uracil, was first synthesized. In 1962, G. Falkson, MD, and E.J. Schulz, MD, reported on skin changes observed in 85 patients being treated with systemic 5-FU for advanced carcinomatosis. They found that 31 of the 85 patients developed sensitivity to sunlight and subsequent disappearance of actinic keratoses in these same patients.

Technology in skin care also was developing in the era just before the launch of Skin & Allergy News. For example, Leon Goldman, MD, then chairman of the department of dermatology at the University of Cincinnati, was the first physician to use a laser for tattoo removal. His publication in 1965 helped to solidify its use, leading him to be “regarded by many in the dermatologic community as the ‘godfather of lasers in medicine and surgery’ ” (Clin Dermatol. 2007;25:434-42).

So, by 1970, dermatology as a field had established itself fully with a strong societal infrastructure, a vibrant base of journals and books, and an evolving set of scientific and technical tools. The launch of Skin & Allergy News (now Dermatology News) that year would chronicle dermatology’s commitment to the development of new therapeutics and technologies in service of patient needs – the stories of which would grace the newspaper’s pages for 5 decades and counting.

[email protected]