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Aiming for Tailored Treatments for Rosacea Subtypes

August 2017

If one attempted to predict the future professional path of Yolanda R. Helfrich, MD, based on her undergraduate pursuits, the odds would have been squarely against them. Dr Helfrich majored in Latin and minored in ancient history at Swarthmore College, a small liberal arts school just outside of Philadelphia. But there’s a twist. “I had wanted to be a doctor since I was a child, so I did all the pre-med requirements that allowed me to apply to medical school,” she explained. Dr Helfrich, now known for furthering developments in rosacea research and treatment, attended the University of Michigan Medical School and also completed her internship in internal medicine and her residency in dermatology at the University of Michigan. She then joined the faculty at the University of Michigan’s Department of Dermatology in 2005, and is now the director of both its Program for Clinical Research in Dermatology and its Residency Training Program.

Working with residents, she told The Dermatologist, is among the most gratifying aspects of her professional life. “When I started my residency, I would never have imagined that I would be an academic dermatologist. However, the rewards of working with and training residents have been life-changing.

There are few things more rewarding than hearing a resident say that he or she has modeled their practice style on your own,” said Dr Helfrich.

Below Dr Helfrich talks about exciting developments in rosacea research, as well as what inspired her to specialize in the field, among other things.

Q. What drew you to dermatology?
A. Dermatology appealed to me for common reasons—I loved being able to diagnose people using only my eyes, and not having to rely on tests or other tools. I loved the variety—the common and the unusual, as well as the range of patients—men, women, infants to the very elderly.

In residency, I participated in clinical research within our department, and my mentors encouraged me to stay on as a faculty member. My career is exclusively focused on medical dermatology; I do not perform any cosmetic or complex surgical work.

Q. What inspired you to focus your research on rosacea?
A. Rosacea pursued me rather than me pursuing rosacea. Our department has a long history of looking at photoaged skin. In practice, we saw many men with really red faces. Some people would call them rosacea, but they often lacked the typical rosacea symptoms of flushing, stinging, and burning; they were just red. These men often had significant photodamage, with histories of skin cancers and actinic keratoses. We decided to examine whether we could find differences, both by history, physical exam, and biopsy, as well as with examination of molecular markers.1

Q. What are some exciting developments in rosacea research and how might patients benefit?
A.  A lot has been happening in rosacea research, which is very exciting. The work of Richard L. Gallo, MD, PhD, on cathelicidin and the innate immune pathways involved in rosacea—especially papulopustular rosacea—has been groundbreaking. The mast cell story is also evolving, and I think that’s very interesting as well. I’m also very intrigued by the intersection between innate immunity, mast cell activation, and neuropeptides.

We still need more research into the mechanism of action of drugs that work in rosacea. We have new drugs in our armamentarium, such as topical ivermectin (Soolantra), topical brimonidine (Mirvaso), and topical oxymetazoline (Rhofade), but I do not think we fully understand why some are more effective than others and how exactly they elicit improvement.
 
Q. Can you provide some highlights of your recent rosacea research for our readers?
A.  Our research really focused on differences between erythematotelangiectatic rosacea and what we termed telangiectatic photoaging—the older, usually male, patient with significant erythema and telangiectasia, but an absence of symptoms or flushing. We found that subjects with rosacea had a greater degree of mast cell degranulation and increased levels of substance P—which causes stinging and burning—as well as calcitonin gene-related-a, a potent vasodilator.1 Clinical signs more characteristic of telangiectatic photoaging were a lateral distribution of erythema and telangiectasia, as opposed to the more central erythema of rosacea, and a lack of prominent flushing symptoms.

Article continues on page 2

Q. What is one of the biggest misconceptions about rosacea?
A.  I think every patient with rosacea comes in with the fear that they will develop prominent rhinophyma. Phymatous rosacea is pretty unusual, and it is quite uncommon for female patients to progress to a phymatous appearance. While there are similarities at a molecular level between the different rosacea subtypes, it is appropriate to reassure most patients that it is unlikely that they will develop the big “W.C. Fields”-type nose in the future.

Q. What does the future landscape of rosacea treatment look like?
A.  I hope that there will be more tailoring of treatment to the form of rosacea with which the patients present. A large number of patients have prominent flushing and erythema, and they do not tend to respond very well to our typical rosacea therapies, such as topical metronidazole, azelaic acid, ivermectin, and sulfur derivatives, and systemic doxycycline and minocycline.

Given the very high costs of all of our dermatologic medications, it will be very important for our patients to receive medications and treatment recommendations that are more likely to work for each patient’s particular subtype of disease.

Q. What professional experience in the realm of dermatology in general and rosacea in particular has been the most personally rewarding? Why?
A. It has been extraordinarily rewarding for me to work with residents. Within our program, residents have the opportunity to participate in clinical research. My rosacea projects rely quite a bit on resident evaluators and residents performing biopsies. I love being able to educate residents on the intricacies of rosacea identification and treatment.

Q. Are there roadblocks that stand in the way of patient compliance to available rosacea treatments?
A.  I worry tremendously about the enormous costs of our dermatology drugs. Many brand name drugs offer various coupons and incentives, but these are not available for patients on Medicare or Medicaid. The cash price of these drugs is also enormous. All of our dermatologic generics are very expensive as well; prices for many generics have skyrocketed in the past 5 years. I’m very excited that there are new therapies for rosacea, but the high prices make them unavailable to many of our patients.

Q. What do you hope your contribution to the field of dermatology will be?
A. Educating residents has been the most rewarding aspect of my career. If I can convey my love of dermatology to scores of residents over the years, teaching them to love the discovery and the mystery of our specialty, I will feel that I have accomplished something truly worthwhile. 

 
Reference
1. Helfrich YR, Maier LE, Cui Y, et al. Clinical, histologic, and molecular analysis of differences between erythematotelangiectatic rosacea and telangiectatic photoaging. JAMA Dermatol. 2015;151(8):825-836.

If one attempted to predict the future professional path of Yolanda R. Helfrich, MD, based on her undergraduate pursuits, the odds would have been squarely against them. Dr Helfrich majored in Latin and minored in ancient history at Swarthmore College, a small liberal arts school just outside of Philadelphia. But there’s a twist. “I had wanted to be a doctor since I was a child, so I did all the pre-med requirements that allowed me to apply to medical school,” she explained. Dr Helfrich, now known for furthering developments in rosacea research and treatment, attended the University of Michigan Medical School and also completed her internship in internal medicine and her residency in dermatology at the University of Michigan. She then joined the faculty at the University of Michigan’s Department of Dermatology in 2005, and is now the director of both its Program for Clinical Research in Dermatology and its Residency Training Program.

Working with residents, she told The Dermatologist, is among the most gratifying aspects of her professional life. “When I started my residency, I would never have imagined that I would be an academic dermatologist. However, the rewards of working with and training residents have been life-changing.

There are few things more rewarding than hearing a resident say that he or she has modeled their practice style on your own,” said Dr Helfrich.

Below Dr Helfrich talks about exciting developments in rosacea research, as well as what inspired her to specialize in the field, among other things.

Q. What drew you to dermatology?
A. Dermatology appealed to me for common reasons—I loved being able to diagnose people using only my eyes, and not having to rely on tests or other tools. I loved the variety—the common and the unusual, as well as the range of patients—men, women, infants to the very elderly.

In residency, I participated in clinical research within our department, and my mentors encouraged me to stay on as a faculty member. My career is exclusively focused on medical dermatology; I do not perform any cosmetic or complex surgical work.

Q. What inspired you to focus your research on rosacea?
A. Rosacea pursued me rather than me pursuing rosacea. Our department has a long history of looking at photoaged skin. In practice, we saw many men with really red faces. Some people would call them rosacea, but they often lacked the typical rosacea symptoms of flushing, stinging, and burning; they were just red. These men often had significant photodamage, with histories of skin cancers and actinic keratoses. We decided to examine whether we could find differences, both by history, physical exam, and biopsy, as well as with examination of molecular markers.1

Q. What are some exciting developments in rosacea research and how might patients benefit?
A.  A lot has been happening in rosacea research, which is very exciting. The work of Richard L. Gallo, MD, PhD, on cathelicidin and the innate immune pathways involved in rosacea—especially papulopustular rosacea—has been groundbreaking. The mast cell story is also evolving, and I think that’s very interesting as well. I’m also very intrigued by the intersection between innate immunity, mast cell activation, and neuropeptides.

We still need more research into the mechanism of action of drugs that work in rosacea. We have new drugs in our armamentarium, such as topical ivermectin (Soolantra), topical brimonidine (Mirvaso), and topical oxymetazoline (Rhofade), but I do not think we fully understand why some are more effective than others and how exactly they elicit improvement.
 
Q. Can you provide some highlights of your recent rosacea research for our readers?
A.  Our research really focused on differences between erythematotelangiectatic rosacea and what we termed telangiectatic photoaging—the older, usually male, patient with significant erythema and telangiectasia, but an absence of symptoms or flushing. We found that subjects with rosacea had a greater degree of mast cell degranulation and increased levels of substance P—which causes stinging and burning—as well as calcitonin gene-related-a, a potent vasodilator.1 Clinical signs more characteristic of telangiectatic photoaging were a lateral distribution of erythema and telangiectasia, as opposed to the more central erythema of rosacea, and a lack of prominent flushing symptoms.

Article continues on page 2

Q. What is one of the biggest misconceptions about rosacea?
A.  I think every patient with rosacea comes in with the fear that they will develop prominent rhinophyma. Phymatous rosacea is pretty unusual, and it is quite uncommon for female patients to progress to a phymatous appearance. While there are similarities at a molecular level between the different rosacea subtypes, it is appropriate to reassure most patients that it is unlikely that they will develop the big “W.C. Fields”-type nose in the future.

Q. What does the future landscape of rosacea treatment look like?
A.  I hope that there will be more tailoring of treatment to the form of rosacea with which the patients present. A large number of patients have prominent flushing and erythema, and they do not tend to respond very well to our typical rosacea therapies, such as topical metronidazole, azelaic acid, ivermectin, and sulfur derivatives, and systemic doxycycline and minocycline.

Given the very high costs of all of our dermatologic medications, it will be very important for our patients to receive medications and treatment recommendations that are more likely to work for each patient’s particular subtype of disease.

Q. What professional experience in the realm of dermatology in general and rosacea in particular has been the most personally rewarding? Why?
A. It has been extraordinarily rewarding for me to work with residents. Within our program, residents have the opportunity to participate in clinical research. My rosacea projects rely quite a bit on resident evaluators and residents performing biopsies. I love being able to educate residents on the intricacies of rosacea identification and treatment.

Q. Are there roadblocks that stand in the way of patient compliance to available rosacea treatments?
A.  I worry tremendously about the enormous costs of our dermatology drugs. Many brand name drugs offer various coupons and incentives, but these are not available for patients on Medicare or Medicaid. The cash price of these drugs is also enormous. All of our dermatologic generics are very expensive as well; prices for many generics have skyrocketed in the past 5 years. I’m very excited that there are new therapies for rosacea, but the high prices make them unavailable to many of our patients.

Q. What do you hope your contribution to the field of dermatology will be?
A. Educating residents has been the most rewarding aspect of my career. If I can convey my love of dermatology to scores of residents over the years, teaching them to love the discovery and the mystery of our specialty, I will feel that I have accomplished something truly worthwhile. 

 
Reference
1. Helfrich YR, Maier LE, Cui Y, et al. Clinical, histologic, and molecular analysis of differences between erythematotelangiectatic rosacea and telangiectatic photoaging. JAMA Dermatol. 2015;151(8):825-836.

If one attempted to predict the future professional path of Yolanda R. Helfrich, MD, based on her undergraduate pursuits, the odds would have been squarely against them. Dr Helfrich majored in Latin and minored in ancient history at Swarthmore College, a small liberal arts school just outside of Philadelphia. But there’s a twist. “I had wanted to be a doctor since I was a child, so I did all the pre-med requirements that allowed me to apply to medical school,” she explained. Dr Helfrich, now known for furthering developments in rosacea research and treatment, attended the University of Michigan Medical School and also completed her internship in internal medicine and her residency in dermatology at the University of Michigan. She then joined the faculty at the University of Michigan’s Department of Dermatology in 2005, and is now the director of both its Program for Clinical Research in Dermatology and its Residency Training Program.

Working with residents, she told The Dermatologist, is among the most gratifying aspects of her professional life. “When I started my residency, I would never have imagined that I would be an academic dermatologist. However, the rewards of working with and training residents have been life-changing.

There are few things more rewarding than hearing a resident say that he or she has modeled their practice style on your own,” said Dr Helfrich.

Below Dr Helfrich talks about exciting developments in rosacea research, as well as what inspired her to specialize in the field, among other things.

Q. What drew you to dermatology?
A. Dermatology appealed to me for common reasons—I loved being able to diagnose people using only my eyes, and not having to rely on tests or other tools. I loved the variety—the common and the unusual, as well as the range of patients—men, women, infants to the very elderly.

In residency, I participated in clinical research within our department, and my mentors encouraged me to stay on as a faculty member. My career is exclusively focused on medical dermatology; I do not perform any cosmetic or complex surgical work.

Q. What inspired you to focus your research on rosacea?
A. Rosacea pursued me rather than me pursuing rosacea. Our department has a long history of looking at photoaged skin. In practice, we saw many men with really red faces. Some people would call them rosacea, but they often lacked the typical rosacea symptoms of flushing, stinging, and burning; they were just red. These men often had significant photodamage, with histories of skin cancers and actinic keratoses. We decided to examine whether we could find differences, both by history, physical exam, and biopsy, as well as with examination of molecular markers.1

Q. What are some exciting developments in rosacea research and how might patients benefit?
A.  A lot has been happening in rosacea research, which is very exciting. The work of Richard L. Gallo, MD, PhD, on cathelicidin and the innate immune pathways involved in rosacea—especially papulopustular rosacea—has been groundbreaking. The mast cell story is also evolving, and I think that’s very interesting as well. I’m also very intrigued by the intersection between innate immunity, mast cell activation, and neuropeptides.

We still need more research into the mechanism of action of drugs that work in rosacea. We have new drugs in our armamentarium, such as topical ivermectin (Soolantra), topical brimonidine (Mirvaso), and topical oxymetazoline (Rhofade), but I do not think we fully understand why some are more effective than others and how exactly they elicit improvement.
 
Q. Can you provide some highlights of your recent rosacea research for our readers?
A.  Our research really focused on differences between erythematotelangiectatic rosacea and what we termed telangiectatic photoaging—the older, usually male, patient with significant erythema and telangiectasia, but an absence of symptoms or flushing. We found that subjects with rosacea had a greater degree of mast cell degranulation and increased levels of substance P—which causes stinging and burning—as well as calcitonin gene-related-a, a potent vasodilator.1 Clinical signs more characteristic of telangiectatic photoaging were a lateral distribution of erythema and telangiectasia, as opposed to the more central erythema of rosacea, and a lack of prominent flushing symptoms.

Article continues on page 2

Q. What is one of the biggest misconceptions about rosacea?
A.  I think every patient with rosacea comes in with the fear that they will develop prominent rhinophyma. Phymatous rosacea is pretty unusual, and it is quite uncommon for female patients to progress to a phymatous appearance. While there are similarities at a molecular level between the different rosacea subtypes, it is appropriate to reassure most patients that it is unlikely that they will develop the big “W.C. Fields”-type nose in the future.

Q. What does the future landscape of rosacea treatment look like?
A.  I hope that there will be more tailoring of treatment to the form of rosacea with which the patients present. A large number of patients have prominent flushing and erythema, and they do not tend to respond very well to our typical rosacea therapies, such as topical metronidazole, azelaic acid, ivermectin, and sulfur derivatives, and systemic doxycycline and minocycline.

Given the very high costs of all of our dermatologic medications, it will be very important for our patients to receive medications and treatment recommendations that are more likely to work for each patient’s particular subtype of disease.

Q. What professional experience in the realm of dermatology in general and rosacea in particular has been the most personally rewarding? Why?
A. It has been extraordinarily rewarding for me to work with residents. Within our program, residents have the opportunity to participate in clinical research. My rosacea projects rely quite a bit on resident evaluators and residents performing biopsies. I love being able to educate residents on the intricacies of rosacea identification and treatment.

Q. Are there roadblocks that stand in the way of patient compliance to available rosacea treatments?
A.  I worry tremendously about the enormous costs of our dermatology drugs. Many brand name drugs offer various coupons and incentives, but these are not available for patients on Medicare or Medicaid. The cash price of these drugs is also enormous. All of our dermatologic generics are very expensive as well; prices for many generics have skyrocketed in the past 5 years. I’m very excited that there are new therapies for rosacea, but the high prices make them unavailable to many of our patients.

Q. What do you hope your contribution to the field of dermatology will be?
A. Educating residents has been the most rewarding aspect of my career. If I can convey my love of dermatology to scores of residents over the years, teaching them to love the discovery and the mystery of our specialty, I will feel that I have accomplished something truly worthwhile. 

 
Reference
1. Helfrich YR, Maier LE, Cui Y, et al. Clinical, histologic, and molecular analysis of differences between erythematotelangiectatic rosacea and telangiectatic photoaging. JAMA Dermatol. 2015;151(8):825-836.

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