Gil Yosipovitch, MD, reflects on the strides being made in the world of eczema and atopic dermatitis, his work on itch as a complex disease, and future plans that look at the effect of itch by targeting pathways in the brain.
To some, itch is simply a symptom, to Gil Yosipovitch, MD, professor of dermatology and director of the Miami Itch Center in the department of dermatology and cutaneous surgery in the Miller School of Medicine, itch is a complex disease. Dr Yosipovitch said there is a lot to be learned from the sensory aspects and characterizations of different types of itch. “The phenotype of itch is not homogeneous,” he said. “Eczema itch is different from psoriasis itch, which is different from neuropathic itch and they are all different from pruritus in lymphoma or uremic itch. There are common denominators, but there are also differences—and if we understand itch better, then we can treat it better.”
Dr Yosipovitch has been awarded dozens of grants from the government, industry, and private foundations to pursue his investigations into the causes and cures of diseases of the skin, with a particular focus on itch. In an interview with The Dermatologist, he reflected on the strides being made in the world of eczema and atopic dermatitis, his current work that focuses on itch as a complex disease, and his future plans to attenuate the effect of itch by targeting pathways in the brain.
Q. What sparked your interest in dermatology, and particularly eczema as the focus of your research and practice?
A. I was an internist and saw the suffering of chronic itch patients with end-stage renal failure on dialysis and decided to work on research in the field of itch. Given that atopic eczema is the No. 1 itchy dermatosis, it led me to do studies in these patients.
Q. What are some of the eczema/atopic dermatitis advances that you are excited about?
A. The targeted treatments such as dupilumab (Dupixent)—which just launched, as well as topicals such as crisaborole (Eucrisa) and the IL-31 inhibitor nemolizumab are exciting. New drugs that are targeting the neural system to reduce itch, such as neurokinin-1 (NK1) inhibitors and k-opioids, are ushering in a new era of effective treatments for chronic itch of atopic eczema and other chronic types of itch.
Q. Where do you see the future treatment of eczema/atopic dermatitis?
A. A revolution in the treatment of chronic pruritus is underway. Recently, much effort in treatment has been placed on targeting the immune system in pruritic diseases. Agents that target IL-4, IL-13, and IL-31, as well as a topical phosphodiesterase-4 inhibitor, have been successfully used in patients with atopic eczema. Agents targeting the nervous system are also showing promise in clinical trials for itch of different types. k-Opioid agonists and combined k-opioid agonists/m-opioid antagonists are being explored as treatment options and NK1 inhibitors have also shown some success in the treatment of itch.
Q. Can you comment on your involvement with the National Eczema Association (NEA) and why the organization is of value to dermatologists and patients?
A. My first brain imaging study in the United States imaging atopic eczema itch was funded by NEA. The results of this study enabled me later on to receive a RO-1 grant from the National Institutes of Health. I later became a scientific board member of NEA and saw firsthand the important ground work in eczema education that the Association is doing for patients and physicians.
Q. What professional endeavor has been the most personally rewarding?
A. Addressing chronic itch as a disease state and exploring different modalities to reduce itch is quite gratifying. Due to the complexity of the different etiologies, cell types, and mediators involved in chronic itch, a combination of topical and systemic therapies addressing peripheral mediators and top-down approaches targeting the brain and spinal cord may be the best strategy of treatment.
Q. What development in the eczema/atopic dermatitis world are you most surprised by?
A.We now understand better that itch is a complex disease. There are a lot of components that are not just skin related in terms of immune or neural elements that we now know are more itch specific and that has opened a whole new field of drugs that are more targeted on the itch pathway—from periphery to nerves—that transfer to the spinal cord up to the brain. The field is booming. Part of it is that we better understand the mechanisms of pathways of itch and that the immune system works very closely with nerves; we still have to better understand how the immune cells work directly with the nerves.
Q. Would you describe some of your current research?
A. Our basic research focuses on mechanisms of chronic itch and scratching in healthy and chronic itch patients, as well as in animal models, and the cross-talk between immune and neural cells. We demonstrated with functional magnetic resonance imaging using arterial spin labeling that scratching an itch led to activation in several brain areas involved in reward and perception. We further found a difference in brain activity during active scratching of an itch by the participant compared with passive scratching by an experimenter.
Several reward-associated areas were activated during active scratching and correlated with pleasure, itch relief, or both. We identified that areas of the brain that respond to reward and pleasure are linked to the ability of a drug known as butorphanol to relieve itch. The findings point to the involvement of the brain’s opioid receptors—widely known for their roles in pain, reward, and addiction in itch relief—potentially opening up new avenues to the development of treatments for chronic itch.1-6
Q. What’s next on your agenda?
A. My group is working on several things. We are moving forward in terms of better understanding both the physiological aspects of itch in different diseases as well as understanding some molecular targets, and we are very interested in developing treatments to reduce itch intensity. We are also looking at gaining a better understanding of mechanisms in the brain, which is the final common pathway of itch transmission, as well as better understanding of some cognitive aspects of itch, such as the pleasure of scratching and how the interaction of scratching and itch work together as a whole, and how we can attenuate it through techniques that target the brain.
Another area we are putting a lot of emphasis on is how the immune cells induce itch on the neural system. In the next couple of years, I think we’ll be contributing findings with respect to cytokines that induce itch and how to they interact with the nerves in these diseases.
References
1. Papoiu AD, Nattkemper LA, Sanders KM, et al. Brain’s reward circuits mediate itch relief. A functional MRI study of active scratching. PLoS One. 2013;8(12):e82389. doi:10.1371/journal.pone.0082389
2. Mochizuki H, Schut C, Nattkemper LA, Yosipovitch G. Brain mechanism of itch in atopic dermatitis and its possible alteration through non-invasive treatments. Allergol Int. 2017;66(1):14-21.
3. Mochizuki H, Papoiu AD, Nattkemper LA, et al. Scratching induces overactivity in motor-related regions and reward system in chronic itch patients. J Invest Dermatol. 2015;135(11):2814-2823.
4. Lloyd DM, McGlone FP, Yosipovitch G. Somatosensory pleasure circuit: from skin to brain and back. Exp Dermatol. 2015;24(5):321-324.
5. Papoiu AD, Kraft RA, Coghill RC, Yosipovitch G. Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study. J Invest Dermatol. 2015;135(2):560-568.
6. Bin Saif GA, Papoiu AD, Banari L, et al. The pleasurability of scratching an itch: a psychophysical and topographical assessment. Br J Dermatol. 2012;166(5):981-985.
Gil Yosipovitch, MD, reflects on the strides being made in the world of eczema and atopic dermatitis, his work on itch as a complex disease, and future plans that look at the effect of itch by targeting pathways in the brain.
To some, itch is simply a symptom, to Gil Yosipovitch, MD, professor of dermatology and director of the Miami Itch Center in the department of dermatology and cutaneous surgery in the Miller School of Medicine, itch is a complex disease. Dr Yosipovitch said there is a lot to be learned from the sensory aspects and characterizations of different types of itch. “The phenotype of itch is not homogeneous,” he said. “Eczema itch is different from psoriasis itch, which is different from neuropathic itch and they are all different from pruritus in lymphoma or uremic itch. There are common denominators, but there are also differences—and if we understand itch better, then we can treat it better.”
Dr Yosipovitch has been awarded dozens of grants from the government, industry, and private foundations to pursue his investigations into the causes and cures of diseases of the skin, with a particular focus on itch. In an interview with The Dermatologist, he reflected on the strides being made in the world of eczema and atopic dermatitis, his current work that focuses on itch as a complex disease, and his future plans to attenuate the effect of itch by targeting pathways in the brain.
Q. What sparked your interest in dermatology, and particularly eczema as the focus of your research and practice?
A. I was an internist and saw the suffering of chronic itch patients with end-stage renal failure on dialysis and decided to work on research in the field of itch. Given that atopic eczema is the No. 1 itchy dermatosis, it led me to do studies in these patients.
Q. What are some of the eczema/atopic dermatitis advances that you are excited about?
A. The targeted treatments such as dupilumab (Dupixent)—which just launched, as well as topicals such as crisaborole (Eucrisa) and the IL-31 inhibitor nemolizumab are exciting. New drugs that are targeting the neural system to reduce itch, such as neurokinin-1 (NK1) inhibitors and k-opioids, are ushering in a new era of effective treatments for chronic itch of atopic eczema and other chronic types of itch.
Q. Where do you see the future treatment of eczema/atopic dermatitis?
A. A revolution in the treatment of chronic pruritus is underway. Recently, much effort in treatment has been placed on targeting the immune system in pruritic diseases. Agents that target IL-4, IL-13, and IL-31, as well as a topical phosphodiesterase-4 inhibitor, have been successfully used in patients with atopic eczema. Agents targeting the nervous system are also showing promise in clinical trials for itch of different types. k-Opioid agonists and combined k-opioid agonists/m-opioid antagonists are being explored as treatment options and NK1 inhibitors have also shown some success in the treatment of itch.
Q. Can you comment on your involvement with the National Eczema Association (NEA) and why the organization is of value to dermatologists and patients?
A. My first brain imaging study in the United States imaging atopic eczema itch was funded by NEA. The results of this study enabled me later on to receive a RO-1 grant from the National Institutes of Health. I later became a scientific board member of NEA and saw firsthand the important ground work in eczema education that the Association is doing for patients and physicians.
Q. What professional endeavor has been the most personally rewarding?
A. Addressing chronic itch as a disease state and exploring different modalities to reduce itch is quite gratifying. Due to the complexity of the different etiologies, cell types, and mediators involved in chronic itch, a combination of topical and systemic therapies addressing peripheral mediators and top-down approaches targeting the brain and spinal cord may be the best strategy of treatment.
Q. What development in the eczema/atopic dermatitis world are you most surprised by?
A.We now understand better that itch is a complex disease. There are a lot of components that are not just skin related in terms of immune or neural elements that we now know are more itch specific and that has opened a whole new field of drugs that are more targeted on the itch pathway—from periphery to nerves—that transfer to the spinal cord up to the brain. The field is booming. Part of it is that we better understand the mechanisms of pathways of itch and that the immune system works very closely with nerves; we still have to better understand how the immune cells work directly with the nerves.
Q. Would you describe some of your current research?
A. Our basic research focuses on mechanisms of chronic itch and scratching in healthy and chronic itch patients, as well as in animal models, and the cross-talk between immune and neural cells. We demonstrated with functional magnetic resonance imaging using arterial spin labeling that scratching an itch led to activation in several brain areas involved in reward and perception. We further found a difference in brain activity during active scratching of an itch by the participant compared with passive scratching by an experimenter.
Several reward-associated areas were activated during active scratching and correlated with pleasure, itch relief, or both. We identified that areas of the brain that respond to reward and pleasure are linked to the ability of a drug known as butorphanol to relieve itch. The findings point to the involvement of the brain’s opioid receptors—widely known for their roles in pain, reward, and addiction in itch relief—potentially opening up new avenues to the development of treatments for chronic itch.1-6
Q. What’s next on your agenda?
A. My group is working on several things. We are moving forward in terms of better understanding both the physiological aspects of itch in different diseases as well as understanding some molecular targets, and we are very interested in developing treatments to reduce itch intensity. We are also looking at gaining a better understanding of mechanisms in the brain, which is the final common pathway of itch transmission, as well as better understanding of some cognitive aspects of itch, such as the pleasure of scratching and how the interaction of scratching and itch work together as a whole, and how we can attenuate it through techniques that target the brain.
Another area we are putting a lot of emphasis on is how the immune cells induce itch on the neural system. In the next couple of years, I think we’ll be contributing findings with respect to cytokines that induce itch and how to they interact with the nerves in these diseases.
References
1. Papoiu AD, Nattkemper LA, Sanders KM, et al. Brain’s reward circuits mediate itch relief. A functional MRI study of active scratching. PLoS One. 2013;8(12):e82389. doi:10.1371/journal.pone.0082389
2. Mochizuki H, Schut C, Nattkemper LA, Yosipovitch G. Brain mechanism of itch in atopic dermatitis and its possible alteration through non-invasive treatments. Allergol Int. 2017;66(1):14-21.
3. Mochizuki H, Papoiu AD, Nattkemper LA, et al. Scratching induces overactivity in motor-related regions and reward system in chronic itch patients. J Invest Dermatol. 2015;135(11):2814-2823.
4. Lloyd DM, McGlone FP, Yosipovitch G. Somatosensory pleasure circuit: from skin to brain and back. Exp Dermatol. 2015;24(5):321-324.
5. Papoiu AD, Kraft RA, Coghill RC, Yosipovitch G. Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study. J Invest Dermatol. 2015;135(2):560-568.
6. Bin Saif GA, Papoiu AD, Banari L, et al. The pleasurability of scratching an itch: a psychophysical and topographical assessment. Br J Dermatol. 2012;166(5):981-985.
Gil Yosipovitch, MD, reflects on the strides being made in the world of eczema and atopic dermatitis, his work on itch as a complex disease, and future plans that look at the effect of itch by targeting pathways in the brain.
To some, itch is simply a symptom, to Gil Yosipovitch, MD, professor of dermatology and director of the Miami Itch Center in the department of dermatology and cutaneous surgery in the Miller School of Medicine, itch is a complex disease. Dr Yosipovitch said there is a lot to be learned from the sensory aspects and characterizations of different types of itch. “The phenotype of itch is not homogeneous,” he said. “Eczema itch is different from psoriasis itch, which is different from neuropathic itch and they are all different from pruritus in lymphoma or uremic itch. There are common denominators, but there are also differences—and if we understand itch better, then we can treat it better.”
Dr Yosipovitch has been awarded dozens of grants from the government, industry, and private foundations to pursue his investigations into the causes and cures of diseases of the skin, with a particular focus on itch. In an interview with The Dermatologist, he reflected on the strides being made in the world of eczema and atopic dermatitis, his current work that focuses on itch as a complex disease, and his future plans to attenuate the effect of itch by targeting pathways in the brain.
Q. What sparked your interest in dermatology, and particularly eczema as the focus of your research and practice?
A. I was an internist and saw the suffering of chronic itch patients with end-stage renal failure on dialysis and decided to work on research in the field of itch. Given that atopic eczema is the No. 1 itchy dermatosis, it led me to do studies in these patients.
Q. What are some of the eczema/atopic dermatitis advances that you are excited about?
A. The targeted treatments such as dupilumab (Dupixent)—which just launched, as well as topicals such as crisaborole (Eucrisa) and the IL-31 inhibitor nemolizumab are exciting. New drugs that are targeting the neural system to reduce itch, such as neurokinin-1 (NK1) inhibitors and k-opioids, are ushering in a new era of effective treatments for chronic itch of atopic eczema and other chronic types of itch.
Q. Where do you see the future treatment of eczema/atopic dermatitis?
A. A revolution in the treatment of chronic pruritus is underway. Recently, much effort in treatment has been placed on targeting the immune system in pruritic diseases. Agents that target IL-4, IL-13, and IL-31, as well as a topical phosphodiesterase-4 inhibitor, have been successfully used in patients with atopic eczema. Agents targeting the nervous system are also showing promise in clinical trials for itch of different types. k-Opioid agonists and combined k-opioid agonists/m-opioid antagonists are being explored as treatment options and NK1 inhibitors have also shown some success in the treatment of itch.
Q. Can you comment on your involvement with the National Eczema Association (NEA) and why the organization is of value to dermatologists and patients?
A. My first brain imaging study in the United States imaging atopic eczema itch was funded by NEA. The results of this study enabled me later on to receive a RO-1 grant from the National Institutes of Health. I later became a scientific board member of NEA and saw firsthand the important ground work in eczema education that the Association is doing for patients and physicians.
Q. What professional endeavor has been the most personally rewarding?
A. Addressing chronic itch as a disease state and exploring different modalities to reduce itch is quite gratifying. Due to the complexity of the different etiologies, cell types, and mediators involved in chronic itch, a combination of topical and systemic therapies addressing peripheral mediators and top-down approaches targeting the brain and spinal cord may be the best strategy of treatment.
Q. What development in the eczema/atopic dermatitis world are you most surprised by?
A.We now understand better that itch is a complex disease. There are a lot of components that are not just skin related in terms of immune or neural elements that we now know are more itch specific and that has opened a whole new field of drugs that are more targeted on the itch pathway—from periphery to nerves—that transfer to the spinal cord up to the brain. The field is booming. Part of it is that we better understand the mechanisms of pathways of itch and that the immune system works very closely with nerves; we still have to better understand how the immune cells work directly with the nerves.
Q. Would you describe some of your current research?
A. Our basic research focuses on mechanisms of chronic itch and scratching in healthy and chronic itch patients, as well as in animal models, and the cross-talk between immune and neural cells. We demonstrated with functional magnetic resonance imaging using arterial spin labeling that scratching an itch led to activation in several brain areas involved in reward and perception. We further found a difference in brain activity during active scratching of an itch by the participant compared with passive scratching by an experimenter.
Several reward-associated areas were activated during active scratching and correlated with pleasure, itch relief, or both. We identified that areas of the brain that respond to reward and pleasure are linked to the ability of a drug known as butorphanol to relieve itch. The findings point to the involvement of the brain’s opioid receptors—widely known for their roles in pain, reward, and addiction in itch relief—potentially opening up new avenues to the development of treatments for chronic itch.1-6
Q. What’s next on your agenda?
A. My group is working on several things. We are moving forward in terms of better understanding both the physiological aspects of itch in different diseases as well as understanding some molecular targets, and we are very interested in developing treatments to reduce itch intensity. We are also looking at gaining a better understanding of mechanisms in the brain, which is the final common pathway of itch transmission, as well as better understanding of some cognitive aspects of itch, such as the pleasure of scratching and how the interaction of scratching and itch work together as a whole, and how we can attenuate it through techniques that target the brain.
Another area we are putting a lot of emphasis on is how the immune cells induce itch on the neural system. In the next couple of years, I think we’ll be contributing findings with respect to cytokines that induce itch and how to they interact with the nerves in these diseases.
References
1. Papoiu AD, Nattkemper LA, Sanders KM, et al. Brain’s reward circuits mediate itch relief. A functional MRI study of active scratching. PLoS One. 2013;8(12):e82389. doi:10.1371/journal.pone.0082389
2. Mochizuki H, Schut C, Nattkemper LA, Yosipovitch G. Brain mechanism of itch in atopic dermatitis and its possible alteration through non-invasive treatments. Allergol Int. 2017;66(1):14-21.
3. Mochizuki H, Papoiu AD, Nattkemper LA, et al. Scratching induces overactivity in motor-related regions and reward system in chronic itch patients. J Invest Dermatol. 2015;135(11):2814-2823.
4. Lloyd DM, McGlone FP, Yosipovitch G. Somatosensory pleasure circuit: from skin to brain and back. Exp Dermatol. 2015;24(5):321-324.
5. Papoiu AD, Kraft RA, Coghill RC, Yosipovitch G. Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study. J Invest Dermatol. 2015;135(2):560-568.
6. Bin Saif GA, Papoiu AD, Banari L, et al. The pleasurability of scratching an itch: a psychophysical and topographical assessment. Br J Dermatol. 2012;166(5):981-985.
