The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).

monkeybusinessimages/Thinkstock

In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).

Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABA_A receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.

Zulresso, an IV infusion, was developed by its manufacturer Sage Therapeutics specifically for moderate to severe postpartum depression. There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.

Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.

Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.

What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.

So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.

Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.

Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.

Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at [email protected].
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).

monkeybusinessimages/Thinkstock

In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).

Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABA_A receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.

Zulresso, an IV infusion, was developed by its manufacturer Sage Therapeutics specifically for moderate to severe postpartum depression. There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.

Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.

Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.

What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.

So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.

Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.

Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.

Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at [email protected].
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

The last decade has brought increasing awareness of the need to effectively screen for postpartum depression, with a majority of states across the country now having some sort of formal program by which women are screened for mood disorder during the postnatal period, typically with scales such as the Edinburgh Postnatal Depression Scale (EPDS).

monkeybusinessimages/Thinkstock

In addition to effective screening is a pressing need for effective referral networks of clinicians who have both the expertise and time to manage the 10%-15% of women who have been identified and who suffer from postpartum psychiatric disorders – both postpartum mood and anxiety disorders. Several studies have suggested that only a small percentage of postpartum women who score with clinically significant level of depressive symptoms actually get to a clinician or, if they do get to a clinician, receive adequate treatment restoring their emotional well-being (J Clin Psychiatry. 2016 Sep;77[9]:1189-200).

Zulresso (brexanolone), a novel new antidepressant medication which recently received Food and Drug Administration approval for the treatment of postpartum depression, is a first-in-class molecule to get such approval. Zulresso is a neurosteroid, an analogue of allopregnanolone and a GABA_A receptor–positive allosteric modulator, a primary inhibitory neurotransmitter in the brain.

Zulresso, an IV infusion, was developed by its manufacturer Sage Therapeutics specifically for moderate to severe postpartum depression. There is every reason to believe that, as a class, this group of neurosteroid molecules are effective in treating depression in other populations aside from women with postpartum depression and hence may not be specific to the postpartum period. For example, recent presentations of preliminary data suggest other neurosteroids such as zuranolone (an oral medication also developed by Sage Therapeutics) is effective for both men and women who have major depression in addition to women suffering from postpartum depression.

Zulresso is approved through a Risk Evaluation and Mitigation Strategy–restricted program and, per that protocol, needs to be administered by a health care provider in a recognized health care setting intravenously over 2.5 days (60 hours). Because of concerns regarding increased sedation, continuous pulse oximetry is required, and this is outlined in a boxed warning in the prescribing information. Zulresso has been classified by the Drug Enforcement Administration (DEA) as a Schedule IV injection and is subject to the prescribing regulations for a controlled substance.

Since Zulresso’s approval, my colleagues and I at the Center for Women’s Mental Health have received numerous queries from patients and colleagues about our clinical impression of this new molecule with a different mechanism of action – a welcome addition to the antidepressant pharmacopeia. The question posed to us essentially is: Where does brexanolone fit into our algorithm for treating women who suffer from postpartum depression? And frequently, the follow-up query is: Because subjects in the clinical trials for this medication included women who had onset of depression either late in pregnancy or during the postpartum period, how specific is brexanolone with respect to being a targeted therapy for postpartum depression, compared with depression encountered in other clinical settings.

What clearly can be stated is that Zulresso has a rapid onset of action and was demonstrated across clinical trials to have sustained benefit up to 30 days after IV administration. The question is whether patients have sustained benefit after 30 days or if this is a medicine to be considered as a “bridge” to other treatment. Data answering that critical clinical question are unavailable at this time. From a clinical standpoint, do patients receive this treatment and get sent home on antidepressants, as we would for patients who receive ECT, often discharging them with prophylactic antidepressants to sustain the benefit of the treatment? Or do patients receive this new medicine with the clinician providing close follow-up, assuming a wait-and-see approach? Because data informing the answer to that question are not available, this decision will be made empirically, frequently factoring in the patient’s past clinical history where presumably more liberal use of antidepressant immediately after the administration of Zulresso will be pursued in those with histories of highly recurrent major depression.

So where might this new medicine fit into the treatment of postpartum depression of moderate severity, or modest to moderate severity? It should be kept in mind that for patients with mild to moderate postpartum depression, there are data supporting the efficacy of cognitive-behavioral therapy (CBT). CBT frequently is pursued with concurrent mobilization of substantial social support with good outcomes. In patients with more severe postpartum depression, there are data supporting the use of antidepressants, and in these patients as well, use of established support from the ever-growing network of community-based support groups and services can be particularly helpful. It is unlikely that Zulresso will be a first-line medication for the treatment of postpartum depression, but it may be particularly appropriate for patients with severe illness who have not responded to other interventions.

Other practical considerations regarding use of Zulresso include the requirement that the medicine be administered in hospitals that have established clinical infrastructure to accommodate this particular population of patients and where pharmacists and other relevant parties in hospitals have accepted the medicine into its drug formulary. While coverage by various insurance policies may vary, the cost of this new medication is substantial, between $24,000 and $34,000 per treatment, according to reports.

Where Zulresso fits into the pharmacopeia for treating postpartum depression may fall well beyond the issues of efficacy. Given all of the attention to this first-in-class medicine, Zulresso has reinforced the growing interest in the substantial prevalence and the morbidity associated with postpartum depression. It is hard to imagine Zulresso being used in cases of more mild to moderate depression, in which there is nonemergent opportunity to pursue options that do not require a new mom to absent herself from homelife with a newborn. However, in picking cases of severe new onset or recurrence of depression in postpartum women, the rapid onset of benefit that was noted within days could be an extraordinary relief and be the beginning of a road to wellness for some women.

Ultimately, the collaboration of patients with their doctors, the realities of cost, and the acceptability of use in various clinical settings will determine how Zulresso is incorporated into seeking treatment to mitigate the suffering associated with postpartum depression. We at the Center for Women’s Mental Health are interested in user experience with respect to this medicine and welcome comments from both patients and their doctors at [email protected].
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. This center was an investigator site for one of the studies supported by Sage Therapeutics, the manufacturer of Zulresso. Dr. Cohen is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School, also in Boston. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

SAN DIEGO – As the gender reassignment surgery market continues to grow in North America, more people are turning to dermatologists for laser hair removal prior to undergoing the procedures.

“In the last year, in terms of hair removal, this has been the biggest change in my practice,” Mathew M. Avram, MD, JD, said at the annual Masters of Aesthetics Symposium.

R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and Melanie Grossman, MD, who practices in New York City, developed laser hair removal in the 1990s, and today laser hair removal stands as the most common laser treatment in medicine, said Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston. He described it as “safe and effective in skilled hands,” requiring about six treatments. Indications are for hypertrichosis, hirsutism (sometimes in the setting of polycystic ovary syndrome), pseudofolliculitis barbae, pilonidal cysts, and gender reassignment surgery.

Laser hair removal works by the extended theory of selective photothermolysis. “You’re targeting by proxy,” Dr. Avram explained. “The laser targets eumelanin in darkly pigmented hairs, with the secondary target being the follicular stem cells. Pigment is a prerequisite for effective treatment. So if there is no pigment in the hair, with current technology, it’s not going to work.”

He advises clinicians to avoid a cookbook approach to fluences when performing laser hair removal. Even though higher fluences have been correlated with greater permanent hair removal, they are also more likely to cause unexpected side effects. “The recommended treatment fluences are often provided with each individual laser device for nonexperienced operators, but I would not recommend doing that,” he said. “You want to evaluate for the desired clinical endpoint of perifollicular erythema and edema. The highest possible tolerated fluence, which yields this endpoint, without any adverse effects, is often the best fluence for treatment.” In 2016, Dr. Avram and his colleagues published a paper that focuses on desirable and therapeutic endpoints when performing laser and light treatments (J Am Acad Dermatol 2016;74[5]:821-33).

The best candidates for laser hair removal are those with light skin color and dark hair. “The more pigment that’s in the hair, the more it’s going to absorb the energy,” he said. Coarse, thick hair responds better than thin vellus hairs, and blond, gray hairs do not respond. A new silver nanoparticle technology is being developed that may improve efficacy for people with blond or gray hair in the future. “Modest initial data showed that it works, but it requires several treatments,” Dr. Avram said.

A past president of the American Society for Laser Medicine and Surgery, Dr. Avram went on to note that laser hair removal is often delegated to nonphysicians and is the most common cause of lawsuits for laser injury. “The rates of lawsuits rise dramatically when delegated to nonphysicians,” he said. “They even rise higher when performed by nonphysicians without supervision such as in medi-spas. Some of the side effects when performed by nonexperienced users can include temporary hyperpigmentation and longterm hypopigmentation.”

One of his clinical pearls is to never perform laser hair removal on suntanned individuals (“you will get obvious, bizarre-appearing hypopigmentation,” he said) and to exercise caution in patients with darker skin types. “If you do a test spot, give it a couple of weeks to see if hyperpigmentation develops,” he advised. “However, their sun exposure may change, and the area you treat with a test spot may be different than the entire area you intend to treat, so don’t think that a test spot is going to guarantee a particular result. You also have to be aware of paradoxical hypertrichosis, where you get more hair growth rather than less.”

Laser hair removal is mandatory prior to neovaginoplasty surgery. Surgeons use skin from the penile shaft and the midscrotum to create the new vagina, Dr. Avram said, so all hair must be removed prior to surgery so that the inside of the new vagina will be free of hair.

“You can use laser or electrolysis for this,” he said. “Electrolysis takes a lot more treatments and is going to be much more tedious than laser hair removal.” Areas to be targeted include all hair on the scrotum and all hair on the penile shaft, plus one inch around the base. “In the perineum, you want to remove hair from the bottom of the scrotum to one inch above the anus in order to clear a 2.5-inch-wide strip,” he said.

For a phalloplasty, surgeons use skin from the underside of arm to create a urethra. This means that all hair should be removed from the crease of the wrist to 15-18 cm up the arm. “You treat the underside of the arm at 4 cm distally and 5.5 cm proximally,” Dr. Avram said. “It should be 15-18 cm in length, and you cannot have any hair that remains within the new urethra.”

To create a penis, surgeons use skin from the prone arm and around. This requires removing hair at 10 cm distally, 13 cm proximally, and 14 cm in length.

Dr. Avram emphasized the importance of patient and staff education and use of preferred pronouns when performing laser hair removal on patients prior to their gender reassignment surgery. “It requires an explanation that this requires multiple treatments and will not remove all hair,” he said. “You can work with an experienced electrologist for nonresponsive hair.”

Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, Soliton, and Zalea. He also reported having ownership and/or shareholder interest in Cytrellis, Invasix, and Zalea and intellectual property rights with Cytrellis.

[email protected]

SAN DIEGO – As the gender reassignment surgery market continues to grow in North America, more people are turning to dermatologists for laser hair removal prior to undergoing the procedures.

“In the last year, in terms of hair removal, this has been the biggest change in my practice,” Mathew M. Avram, MD, JD, said at the annual Masters of Aesthetics Symposium.

R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and Melanie Grossman, MD, who practices in New York City, developed laser hair removal in the 1990s, and today laser hair removal stands as the most common laser treatment in medicine, said Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston. He described it as “safe and effective in skilled hands,” requiring about six treatments. Indications are for hypertrichosis, hirsutism (sometimes in the setting of polycystic ovary syndrome), pseudofolliculitis barbae, pilonidal cysts, and gender reassignment surgery.

Laser hair removal works by the extended theory of selective photothermolysis. “You’re targeting by proxy,” Dr. Avram explained. “The laser targets eumelanin in darkly pigmented hairs, with the secondary target being the follicular stem cells. Pigment is a prerequisite for effective treatment. So if there is no pigment in the hair, with current technology, it’s not going to work.”

He advises clinicians to avoid a cookbook approach to fluences when performing laser hair removal. Even though higher fluences have been correlated with greater permanent hair removal, they are also more likely to cause unexpected side effects. “The recommended treatment fluences are often provided with each individual laser device for nonexperienced operators, but I would not recommend doing that,” he said. “You want to evaluate for the desired clinical endpoint of perifollicular erythema and edema. The highest possible tolerated fluence, which yields this endpoint, without any adverse effects, is often the best fluence for treatment.” In 2016, Dr. Avram and his colleagues published a paper that focuses on desirable and therapeutic endpoints when performing laser and light treatments (J Am Acad Dermatol 2016;74[5]:821-33).

The best candidates for laser hair removal are those with light skin color and dark hair. “The more pigment that’s in the hair, the more it’s going to absorb the energy,” he said. Coarse, thick hair responds better than thin vellus hairs, and blond, gray hairs do not respond. A new silver nanoparticle technology is being developed that may improve efficacy for people with blond or gray hair in the future. “Modest initial data showed that it works, but it requires several treatments,” Dr. Avram said.

A past president of the American Society for Laser Medicine and Surgery, Dr. Avram went on to note that laser hair removal is often delegated to nonphysicians and is the most common cause of lawsuits for laser injury. “The rates of lawsuits rise dramatically when delegated to nonphysicians,” he said. “They even rise higher when performed by nonphysicians without supervision such as in medi-spas. Some of the side effects when performed by nonexperienced users can include temporary hyperpigmentation and longterm hypopigmentation.”

One of his clinical pearls is to never perform laser hair removal on suntanned individuals (“you will get obvious, bizarre-appearing hypopigmentation,” he said) and to exercise caution in patients with darker skin types. “If you do a test spot, give it a couple of weeks to see if hyperpigmentation develops,” he advised. “However, their sun exposure may change, and the area you treat with a test spot may be different than the entire area you intend to treat, so don’t think that a test spot is going to guarantee a particular result. You also have to be aware of paradoxical hypertrichosis, where you get more hair growth rather than less.”

Laser hair removal is mandatory prior to neovaginoplasty surgery. Surgeons use skin from the penile shaft and the midscrotum to create the new vagina, Dr. Avram said, so all hair must be removed prior to surgery so that the inside of the new vagina will be free of hair.

“You can use laser or electrolysis for this,” he said. “Electrolysis takes a lot more treatments and is going to be much more tedious than laser hair removal.” Areas to be targeted include all hair on the scrotum and all hair on the penile shaft, plus one inch around the base. “In the perineum, you want to remove hair from the bottom of the scrotum to one inch above the anus in order to clear a 2.5-inch-wide strip,” he said.

For a phalloplasty, surgeons use skin from the underside of arm to create a urethra. This means that all hair should be removed from the crease of the wrist to 15-18 cm up the arm. “You treat the underside of the arm at 4 cm distally and 5.5 cm proximally,” Dr. Avram said. “It should be 15-18 cm in length, and you cannot have any hair that remains within the new urethra.”

To create a penis, surgeons use skin from the prone arm and around. This requires removing hair at 10 cm distally, 13 cm proximally, and 14 cm in length.

Dr. Avram emphasized the importance of patient and staff education and use of preferred pronouns when performing laser hair removal on patients prior to their gender reassignment surgery. “It requires an explanation that this requires multiple treatments and will not remove all hair,” he said. “You can work with an experienced electrologist for nonresponsive hair.”

Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, Soliton, and Zalea. He also reported having ownership and/or shareholder interest in Cytrellis, Invasix, and Zalea and intellectual property rights with Cytrellis.

[email protected]

SAN DIEGO – As the gender reassignment surgery market continues to grow in North America, more people are turning to dermatologists for laser hair removal prior to undergoing the procedures.

“In the last year, in terms of hair removal, this has been the biggest change in my practice,” Mathew M. Avram, MD, JD, said at the annual Masters of Aesthetics Symposium.

R. Rox Anderson, MD, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, and Melanie Grossman, MD, who practices in New York City, developed laser hair removal in the 1990s, and today laser hair removal stands as the most common laser treatment in medicine, said Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital, Boston. He described it as “safe and effective in skilled hands,” requiring about six treatments. Indications are for hypertrichosis, hirsutism (sometimes in the setting of polycystic ovary syndrome), pseudofolliculitis barbae, pilonidal cysts, and gender reassignment surgery.

Laser hair removal works by the extended theory of selective photothermolysis. “You’re targeting by proxy,” Dr. Avram explained. “The laser targets eumelanin in darkly pigmented hairs, with the secondary target being the follicular stem cells. Pigment is a prerequisite for effective treatment. So if there is no pigment in the hair, with current technology, it’s not going to work.”

He advises clinicians to avoid a cookbook approach to fluences when performing laser hair removal. Even though higher fluences have been correlated with greater permanent hair removal, they are also more likely to cause unexpected side effects. “The recommended treatment fluences are often provided with each individual laser device for nonexperienced operators, but I would not recommend doing that,” he said. “You want to evaluate for the desired clinical endpoint of perifollicular erythema and edema. The highest possible tolerated fluence, which yields this endpoint, without any adverse effects, is often the best fluence for treatment.” In 2016, Dr. Avram and his colleagues published a paper that focuses on desirable and therapeutic endpoints when performing laser and light treatments (J Am Acad Dermatol 2016;74[5]:821-33).

The best candidates for laser hair removal are those with light skin color and dark hair. “The more pigment that’s in the hair, the more it’s going to absorb the energy,” he said. Coarse, thick hair responds better than thin vellus hairs, and blond, gray hairs do not respond. A new silver nanoparticle technology is being developed that may improve efficacy for people with blond or gray hair in the future. “Modest initial data showed that it works, but it requires several treatments,” Dr. Avram said.

A past president of the American Society for Laser Medicine and Surgery, Dr. Avram went on to note that laser hair removal is often delegated to nonphysicians and is the most common cause of lawsuits for laser injury. “The rates of lawsuits rise dramatically when delegated to nonphysicians,” he said. “They even rise higher when performed by nonphysicians without supervision such as in medi-spas. Some of the side effects when performed by nonexperienced users can include temporary hyperpigmentation and longterm hypopigmentation.”

One of his clinical pearls is to never perform laser hair removal on suntanned individuals (“you will get obvious, bizarre-appearing hypopigmentation,” he said) and to exercise caution in patients with darker skin types. “If you do a test spot, give it a couple of weeks to see if hyperpigmentation develops,” he advised. “However, their sun exposure may change, and the area you treat with a test spot may be different than the entire area you intend to treat, so don’t think that a test spot is going to guarantee a particular result. You also have to be aware of paradoxical hypertrichosis, where you get more hair growth rather than less.”

Laser hair removal is mandatory prior to neovaginoplasty surgery. Surgeons use skin from the penile shaft and the midscrotum to create the new vagina, Dr. Avram said, so all hair must be removed prior to surgery so that the inside of the new vagina will be free of hair.

“You can use laser or electrolysis for this,” he said. “Electrolysis takes a lot more treatments and is going to be much more tedious than laser hair removal.” Areas to be targeted include all hair on the scrotum and all hair on the penile shaft, plus one inch around the base. “In the perineum, you want to remove hair from the bottom of the scrotum to one inch above the anus in order to clear a 2.5-inch-wide strip,” he said.

For a phalloplasty, surgeons use skin from the underside of arm to create a urethra. This means that all hair should be removed from the crease of the wrist to 15-18 cm up the arm. “You treat the underside of the arm at 4 cm distally and 5.5 cm proximally,” Dr. Avram said. “It should be 15-18 cm in length, and you cannot have any hair that remains within the new urethra.”

To create a penis, surgeons use skin from the prone arm and around. This requires removing hair at 10 cm distally, 13 cm proximally, and 14 cm in length.

Dr. Avram emphasized the importance of patient and staff education and use of preferred pronouns when performing laser hair removal on patients prior to their gender reassignment surgery. “It requires an explanation that this requires multiple treatments and will not remove all hair,” he said. “You can work with an experienced electrologist for nonresponsive hair.”

Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, Soliton, and Zalea. He also reported having ownership and/or shareholder interest in Cytrellis, Invasix, and Zalea and intellectual property rights with Cytrellis.

[email protected]

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

Approximately two-thirds of adults with uveitis achieved inflammation control after 6 months on either methotrexate or mycophenolate alongside a reduction in corticosteroid use in an international, multicenter, open-label, randomized trial.

“The findings of this trial have implications for clinical practice because they provide scientific justification that mycophenolate mofetil is not more effective than methotrexate as a corticosteroid-sparing immunosuppressive therapy for uveitis,” wrote S.R. Rathinam, MD, PhD, of Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, and colleagues.

Although corticosteroid therapy is the first-line treatment for uveitis, adverse effects limit long-term use. Mycophenolate mofetil and methotrexate are options for corticosteroid-sparing immunosuppressive therapy for uveitis, but their effectiveness has not been compared until the current study, they said.

In the First-line Antimetabolites as Steroid-sparing Treatment (FAST) trial published Sept. 10 in JAMA, the researchers randomized 216 adults with uveitis (a total of 407 eyes with uveitis) to 25 mg of weekly oral methotrexate or 1.5 g of twice-daily oral mycophenolate mofetil at nine referral eye care centers in India, the United States, Australia, Saudi Arabia, and Mexico; the investigators were masked to the treatment assignment.

Patients with treatment success continued taking their randomized medication for another 6 months. If treatment failed, patients switched to the other antimetabolite with another 6-month follow-up. Overall, 84%-93% in each group had bilateral uveitis. Forty-six patients (21%) had intermediate uveitis only or anterior uveitis and intermediate uveitis, and 170 patients (79%) had posterior uveitis or panuveitis. The median age of the patients was 36 years in the methotrexate group and 41 years in the mycophenolate group; other demographic characteristics were similar between the groups.

SOURCE: Rathinam SR et al. JAMA. 2019;322(10):936-45. doi: 10.1001/jama.2019.12618.

The Diagnosis: Bullous Systemic Lupus Erythematosus  

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease that affects patients with systemic lupus erythematosus (SLE). Our patient had a several-year history of SLE and was being managed by a rheumatologist. She was taking hydroxychloroquine at the time of the flare. Although BSLE tends to present in those with SLE that has already been diagnosed, BSLE has been reported as a possible initial manifestation of SLE.¹  

Bullous systemic lupus erythematosus is estimated to occur in less than 5% of patients with SLE and is more common in black women between the second and third decades of life,² though it also can be seen in the pediatric population.³ The lesions of BSLE usually present as subepidermal blisters often located on the face, neck, and arms on an erythematous or possibly urticarial base. Although non-BSLE vesiculobullous eruptions may be seen in patients with SLE, BSLE is differentiated from these other eruptions by its appearance on sun-exposed and non-sun-exposed areas of the body, while other vesiculobullous eruptions associated with SLE typically are limited to sun-exposed sites.⁴  

Due to its clinical presentation overlapping with several vesiculobullous conditions, a set of diagnostic criteria have been suggested for BSLE, including the following: (1) fulfillment of the American Rheumatism Association's criteria for SLE⁵; (2) a new-onset vesiculobullous eruption, primarily on sun-exposed skin; (3) histology showing a subepidermal blister with a predominantly neutrophilic infiltrate; (4) presence of IgG, IgA, IgM, and C3 at the basement membrane zone; (5) evidence of antibodies to type VII collagen; and (6) immunoelectron microscopy showing codistribution of immunoglobulin deposits with anchoring fibrils/type VII collagen. To meet the diagnosis of type I BSLE, all 6 criteria must be satisfied. To meet the diagnosis of type II BSLE, only criteria 1 to 4 need to be satisfied.⁶  

Patients with BSLE may be presumed to have a different but clinically similar vesiculobullous condition (eg, bullous pemphigoid, cutaneous manifestations of SLE) and may be started on systemic corticosteroids. However, BSLE patients often do not show great improvement while on corticosteroids and may even flare shortly after beginning systemic corticosteroid treatment. The current treatment of choice for BSLE is dapsone, a sulfa drug that is thought to exhibit its anti-inflammatory properties via the inhibition of the alternative pathway of the complement system and through the inhibition of polymorphonuclear leukocyte functions.⁷ A response to dapsone helps differentiate BSLE from histopathologically and immunopathologically identical conditions such as epidermolysis bullosa acquisita.⁴ Bullous systemic lupus erythematosus can be differentiated from dermatitis herpetiformis with the presence of antigliadin and antitissue transglutaminase antibodies, which are found in the latter.  Additionally, BSLE may show the presence of IgG and IgM deposition in addition to IgA deposition, as opposed to dermatitis herpetiformis where only IgA is found.⁸ The presence of these additional antibody depositions also help differentiate BSLE from linear IgA bullous dermatosis (LABD), as LABD will only have IgA depositions and often presents with an annular, crown of jewels-like appearance.  Finally, there is a well-described phenomenon of LABD being drug induced, particularly after a course of vancomycin,⁹ and such an association with vancomycin has not been documented for BSLE. 

Our patient was diagnosed with BSLE following the flare approximately 1.5 years prior to the current presentation. She had been started on dapsone 75 mg daily at that time and was taking 75 mg at the time of presentation. She was admitted and treated as an inpatient with high-dose (1 mg/kg) intravenous prednisone due to the extensive current flare. 

The Diagnosis: Bullous Systemic Lupus Erythematosus  

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease that affects patients with systemic lupus erythematosus (SLE). Our patient had a several-year history of SLE and was being managed by a rheumatologist. She was taking hydroxychloroquine at the time of the flare. Although BSLE tends to present in those with SLE that has already been diagnosed, BSLE has been reported as a possible initial manifestation of SLE.¹  

Bullous systemic lupus erythematosus is estimated to occur in less than 5% of patients with SLE and is more common in black women between the second and third decades of life,² though it also can be seen in the pediatric population.³ The lesions of BSLE usually present as subepidermal blisters often located on the face, neck, and arms on an erythematous or possibly urticarial base. Although non-BSLE vesiculobullous eruptions may be seen in patients with SLE, BSLE is differentiated from these other eruptions by its appearance on sun-exposed and non-sun-exposed areas of the body, while other vesiculobullous eruptions associated with SLE typically are limited to sun-exposed sites.⁴  

Due to its clinical presentation overlapping with several vesiculobullous conditions, a set of diagnostic criteria have been suggested for BSLE, including the following: (1) fulfillment of the American Rheumatism Association's criteria for SLE⁵; (2) a new-onset vesiculobullous eruption, primarily on sun-exposed skin; (3) histology showing a subepidermal blister with a predominantly neutrophilic infiltrate; (4) presence of IgG, IgA, IgM, and C3 at the basement membrane zone; (5) evidence of antibodies to type VII collagen; and (6) immunoelectron microscopy showing codistribution of immunoglobulin deposits with anchoring fibrils/type VII collagen. To meet the diagnosis of type I BSLE, all 6 criteria must be satisfied. To meet the diagnosis of type II BSLE, only criteria 1 to 4 need to be satisfied.⁶  

Patients with BSLE may be presumed to have a different but clinically similar vesiculobullous condition (eg, bullous pemphigoid, cutaneous manifestations of SLE) and may be started on systemic corticosteroids. However, BSLE patients often do not show great improvement while on corticosteroids and may even flare shortly after beginning systemic corticosteroid treatment. The current treatment of choice for BSLE is dapsone, a sulfa drug that is thought to exhibit its anti-inflammatory properties via the inhibition of the alternative pathway of the complement system and through the inhibition of polymorphonuclear leukocyte functions.⁷ A response to dapsone helps differentiate BSLE from histopathologically and immunopathologically identical conditions such as epidermolysis bullosa acquisita.⁴ Bullous systemic lupus erythematosus can be differentiated from dermatitis herpetiformis with the presence of antigliadin and antitissue transglutaminase antibodies, which are found in the latter.  Additionally, BSLE may show the presence of IgG and IgM deposition in addition to IgA deposition, as opposed to dermatitis herpetiformis where only IgA is found.⁸ The presence of these additional antibody depositions also help differentiate BSLE from linear IgA bullous dermatosis (LABD), as LABD will only have IgA depositions and often presents with an annular, crown of jewels-like appearance.  Finally, there is a well-described phenomenon of LABD being drug induced, particularly after a course of vancomycin,⁹ and such an association with vancomycin has not been documented for BSLE. 

Our patient was diagnosed with BSLE following the flare approximately 1.5 years prior to the current presentation. She had been started on dapsone 75 mg daily at that time and was taking 75 mg at the time of presentation. She was admitted and treated as an inpatient with high-dose (1 mg/kg) intravenous prednisone due to the extensive current flare. 

The Diagnosis: Bullous Systemic Lupus Erythematosus  

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease that affects patients with systemic lupus erythematosus (SLE). Our patient had a several-year history of SLE and was being managed by a rheumatologist. She was taking hydroxychloroquine at the time of the flare. Although BSLE tends to present in those with SLE that has already been diagnosed, BSLE has been reported as a possible initial manifestation of SLE.¹  

Bullous systemic lupus erythematosus is estimated to occur in less than 5% of patients with SLE and is more common in black women between the second and third decades of life,² though it also can be seen in the pediatric population.³ The lesions of BSLE usually present as subepidermal blisters often located on the face, neck, and arms on an erythematous or possibly urticarial base. Although non-BSLE vesiculobullous eruptions may be seen in patients with SLE, BSLE is differentiated from these other eruptions by its appearance on sun-exposed and non-sun-exposed areas of the body, while other vesiculobullous eruptions associated with SLE typically are limited to sun-exposed sites.⁴  

Due to its clinical presentation overlapping with several vesiculobullous conditions, a set of diagnostic criteria have been suggested for BSLE, including the following: (1) fulfillment of the American Rheumatism Association's criteria for SLE⁵; (2) a new-onset vesiculobullous eruption, primarily on sun-exposed skin; (3) histology showing a subepidermal blister with a predominantly neutrophilic infiltrate; (4) presence of IgG, IgA, IgM, and C3 at the basement membrane zone; (5) evidence of antibodies to type VII collagen; and (6) immunoelectron microscopy showing codistribution of immunoglobulin deposits with anchoring fibrils/type VII collagen. To meet the diagnosis of type I BSLE, all 6 criteria must be satisfied. To meet the diagnosis of type II BSLE, only criteria 1 to 4 need to be satisfied.⁶  

Patients with BSLE may be presumed to have a different but clinically similar vesiculobullous condition (eg, bullous pemphigoid, cutaneous manifestations of SLE) and may be started on systemic corticosteroids. However, BSLE patients often do not show great improvement while on corticosteroids and may even flare shortly after beginning systemic corticosteroid treatment. The current treatment of choice for BSLE is dapsone, a sulfa drug that is thought to exhibit its anti-inflammatory properties via the inhibition of the alternative pathway of the complement system and through the inhibition of polymorphonuclear leukocyte functions.⁷ A response to dapsone helps differentiate BSLE from histopathologically and immunopathologically identical conditions such as epidermolysis bullosa acquisita.⁴ Bullous systemic lupus erythematosus can be differentiated from dermatitis herpetiformis with the presence of antigliadin and antitissue transglutaminase antibodies, which are found in the latter.  Additionally, BSLE may show the presence of IgG and IgM deposition in addition to IgA deposition, as opposed to dermatitis herpetiformis where only IgA is found.⁸ The presence of these additional antibody depositions also help differentiate BSLE from linear IgA bullous dermatosis (LABD), as LABD will only have IgA depositions and often presents with an annular, crown of jewels-like appearance.  Finally, there is a well-described phenomenon of LABD being drug induced, particularly after a course of vancomycin,⁹ and such an association with vancomycin has not been documented for BSLE. 

Our patient was diagnosed with BSLE following the flare approximately 1.5 years prior to the current presentation. She had been started on dapsone 75 mg daily at that time and was taking 75 mg at the time of presentation. She was admitted and treated as an inpatient with high-dose (1 mg/kg) intravenous prednisone due to the extensive current flare. 

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

To the Editor:

A 43-year-old woman presented with a mole on the central back that had been present since childhood and had changed and grown over the last few years. The patient reported that her 2-year-old rescue dog frequently sniffed the mole and would subsequently get agitated and try to scratch and bite the lesion. This behavior prompted the patient to visit a dermatologist.

She reported no personal history of melanoma or nonmelanoma skin cancer, tanning booth exposure, blistering sunburns, or use of immunosuppressant medications. Her family history was remarkable for basal cell carcinoma in her father but no family history of melanoma. Physical examination revealed a 1.2×1.5-cm brown patch along with a 1×1-cm ulcerated nodule on the lower aspect of the lesion (Figure 1). Dermoscopy showed a blue-white veil and an irregular vascular pattern (Figure 2). No cervical, axillary, or inguinal lymphadenopathy was appreciated on physical examination. Reflectance confocal microscopy showed pagetoid spread of atypical round melanocytes as well as melanocytes in the stratum corneum (Figure 3).

The patient was referred to a surgical oncologist for wide local excision and sentinel lymph node biopsy. Pathology showed a 4-mm-thick melanoma with numerous positive lymph nodes (Figure 4). The patient subsequently underwent a right axillary lymphadenectomy and was diagnosed with stage IIIB malignant melanoma. After surgery, the patient reported that her dog would now sniff her back and calmly rest his head in her lap.

Both anecdotal and systematic evidence have emerged on the role of canine olfaction in the detection of lung, breast, colorectal, ovarian, prostate, and skin cancers, including malignant melanoma.^1-6 A 1989 case report described a woman who was prompted to seek dermatologic evaluation of a pigmented lesion because her dog consistently targeted the lesion. Excision and subsequent histopathologic examination of the lesion revealed that it was malignant melanoma.⁵ Another case report described a patient whose dog, which was not trained to detect cancers in humans, persistently licked a lesion behind the patient’s ear that eventually was found to be malignant melanoma.⁶ These reports have inspired considerable research interest regarding canine olfaction as a potential method to noninvasively screen for and even diagnose malignant melanomas in humans.

Both physiologic and pathologic metabolic processes result in the production of volatile organic compounds (VOCs), or small odorant molecules that evaporate at normal temperatures and pressures.¹ Individual cells release VOCs in extremely low concentrations into the blood, urine, feces, and breath, as well as onto the skin’s surface, but there are methods for detecting these VOCs, including gas chromatography–mass spectrometry and canine olfaction.^7,8 Pathologic processes, such as infection and malignancy, result in irregular protein synthesis and metabolism, producing new VOCs or differing concentrations of VOCs as compared to normal processes.¹

Dimethyl disulfide and dimethyl trisulfide compounds have been identified in malignant melanoma, and these compounds are not produced by normal melanocytes.⁷ Furthermore, malignant melanoma produces differing quantities of these compounds as compared to normal melanocytes, including isovaleric acid, 2-methylbutyric acid, isoamyl alcohol (3-methyl-1-butanol), and 2-methyl-1-butanol, resulting in a distinct odorant profile that previously has been detected via canine olfaction.⁷ Canine olfaction can identify odorant molecules at up to 1 part per trillion (a magnitude more sensitive than the currently available gas chromatography–mass spectrometry technologies) and can detect the production of new VOCs or altered VOC ratios due to pathologic processes.¹ Systematic studies with dogs that are trained to detect cancers in humans have shown that canine olfaction correctly identified malignant melanomas against healthy skin, benign nevi, and even basal cell carcinomas at higher rates than what would have been expected by chance alone.^2,3

Canine olfaction can identify new or altered ratios of odorant VOCs associated with pathologic metabolic processes, and canines can be trained to target odor profiles associated with specific diseases.¹ Canine olfaction for melanoma screening and diagnosis may seem appealing, as it provides an easily transportable, real-time, low-cost method compared to other techniques such as gas chromatography–mass spectrometry.¹ Although preliminary results have shown that canine olfaction detects melanoma at higher rates than would be expected by chance alone, these findings have not approached clinical utility for the widespread use of canine olfaction as a screening method for melanoma.^2,3,9 Further studies are needed to understand the role of canine olfaction in melanoma screening and diagnosis as well as to explore methods to optimize sensitivity and specificity. Until then, patients and dermatologists should not ignore the behavior of dogs toward skin lesions. Dogs may be beneficial in the detection of melanoma and help save lives, as was seen in our case.

PARIS – Middle-aged adults with a body mass index of 25-29 kg/m² had a significantly better adjusted survival during a median follow-up of nearly 10 years than did people with a “normal” body mass index of 20-24 kg/m² in a worldwide study of more than 140,000. This finding suggests the current, widely accepted definition of normal body mass index is wrong.*

Mitchel L. Zoler/MDedge News

The new findings suggest that the current definition of a “healthy” body mass index (BMI) “should be re-evaluated,” Darryl P. Leong, MBBS, said at the annual Congress of the European Society of Cardiology. The analysis also identified a BMI specifically of 27 kg/m² as associated with optimal survival among both women and men, “clearly outside the range of 20 to less than 25 kg/m² that is considered normal,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Dr. Leong cited three potential explanations for why the new study identified optimal survival with a BMI of 25 to less than 30 kg/m² among people who were 35-70 years old when they entered the study and were followed for a median of 9.5 years: The current study collected data and adjusted the results using a wider range of potential confounders than in prior studies, the data reflect the impact of contemporary interventions to reduce cardiovascular disease illness and death while past studies relied on data from earlier times when less cardiovascular disease protection occurred, and the current study included people from lower-income countries, although the finding is just as applicable to people who live in high-income countries, who were also included in the study population, noted Salim Yusuf, MBBS, principal investigator for the study.

A BMI of 20-24 kg/m² “is actually low and harmful,” noted Dr. Yusuf in an interview. Despite recent data consistently showing better survival among people with a BMI of 25-29 kg/m², panels that have recently written weight guidelines are “ossified” and “refuse to accept” the implications of these findings, said Dr. Yusuf, professor of medicine at McMaster and executive director of the Population Health Research Institute.

The results of the analyses that Dr. Leong reported also showed that BMI paled as a prognosticator for survival when compared with two other assessments of weight: waist/hip ratio, and even more powerful prognostically, a novel measure developed for this analysis that calculates the ratio of hand-grip strength/body weight. Waist/hip ratio adds the dimension of the location of body fat rather than just the amount, and the ratio of grip strength/body weight assesses the contribution of muscle mass to overall weight, noted Dr. Leong. He reported an optimal waist/hip ratio for survival of 0.83 in women and 0.93 in men, and an optimal strength/weight ratio of 0.42 in women and 0.50 in men. This means that a man whose hand-grip strength (measured in kg) is half of the person’s body weight has the best prospect for survival.
 
The study used data collected in PURE (Prospective Urban Rural Epidemiology Study) on 142,410 people aged 35-70 years from any one of four high-income countries, 12 middle-income countries, and five low-income countries. The study excluded people who had at baseline known coronary artery disease, stroke, heart failure, or cancer, and the adjusted analysis controlled for age, sex, region, education, activity, alcohol and tobacco use, and the baseline prevalence of hypertension and diabetes. During follow-up, 9,712 of these people died.

The researchers saw a nadir for mortality among people with a BMI of 25-29 kg/m² for both cardiovascular and noncardiovascular deaths. In addition, the link between total mortality and BMI was strongest in the subgroup of people on one or more treatments aimed at preventing cardiovascular disease, while it essentially disappeared among people not receiving any cardiovascular disease preventive measures, highlighting that the relationship now identified depends on a context of overall cardiovascular disease risk reduction, Dr. Leong said. The results also showed a very clear, direct, linear relationship between higher BMI and both the incidence of diabetes and cardiovascular disease, as well as increased all-cause and noncardiovascular mortality among people with a BMI of less than 20 kg/m².

Dr. Yusuf discussed the results of the analysis in a video interview.

The PURE study has received partial funding from unrestricted grants from several drug companies. Dr. Leong has been an advisor to Ferring Pharmaceuticals and has been a speaker on behalf of Janssen. Dr. Yusuf had no disclosures.

[email protected]

This story was updated 9/19/2019.

PARIS – Middle-aged adults with a body mass index of 25-29 kg/m² had a significantly better adjusted survival during a median follow-up of nearly 10 years than did people with a “normal” body mass index of 20-24 kg/m² in a worldwide study of more than 140,000. This finding suggests the current, widely accepted definition of normal body mass index is wrong.*

Mitchel L. Zoler/MDedge News

The new findings suggest that the current definition of a “healthy” body mass index (BMI) “should be re-evaluated,” Darryl P. Leong, MBBS, said at the annual Congress of the European Society of Cardiology. The analysis also identified a BMI specifically of 27 kg/m² as associated with optimal survival among both women and men, “clearly outside the range of 20 to less than 25 kg/m² that is considered normal,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Dr. Leong cited three potential explanations for why the new study identified optimal survival with a BMI of 25 to less than 30 kg/m² among people who were 35-70 years old when they entered the study and were followed for a median of 9.5 years: The current study collected data and adjusted the results using a wider range of potential confounders than in prior studies, the data reflect the impact of contemporary interventions to reduce cardiovascular disease illness and death while past studies relied on data from earlier times when less cardiovascular disease protection occurred, and the current study included people from lower-income countries, although the finding is just as applicable to people who live in high-income countries, who were also included in the study population, noted Salim Yusuf, MBBS, principal investigator for the study.

A BMI of 20-24 kg/m² “is actually low and harmful,” noted Dr. Yusuf in an interview. Despite recent data consistently showing better survival among people with a BMI of 25-29 kg/m², panels that have recently written weight guidelines are “ossified” and “refuse to accept” the implications of these findings, said Dr. Yusuf, professor of medicine at McMaster and executive director of the Population Health Research Institute.

The results of the analyses that Dr. Leong reported also showed that BMI paled as a prognosticator for survival when compared with two other assessments of weight: waist/hip ratio, and even more powerful prognostically, a novel measure developed for this analysis that calculates the ratio of hand-grip strength/body weight. Waist/hip ratio adds the dimension of the location of body fat rather than just the amount, and the ratio of grip strength/body weight assesses the contribution of muscle mass to overall weight, noted Dr. Leong. He reported an optimal waist/hip ratio for survival of 0.83 in women and 0.93 in men, and an optimal strength/weight ratio of 0.42 in women and 0.50 in men. This means that a man whose hand-grip strength (measured in kg) is half of the person’s body weight has the best prospect for survival.
 
The study used data collected in PURE (Prospective Urban Rural Epidemiology Study) on 142,410 people aged 35-70 years from any one of four high-income countries, 12 middle-income countries, and five low-income countries. The study excluded people who had at baseline known coronary artery disease, stroke, heart failure, or cancer, and the adjusted analysis controlled for age, sex, region, education, activity, alcohol and tobacco use, and the baseline prevalence of hypertension and diabetes. During follow-up, 9,712 of these people died.

The researchers saw a nadir for mortality among people with a BMI of 25-29 kg/m² for both cardiovascular and noncardiovascular deaths. In addition, the link between total mortality and BMI was strongest in the subgroup of people on one or more treatments aimed at preventing cardiovascular disease, while it essentially disappeared among people not receiving any cardiovascular disease preventive measures, highlighting that the relationship now identified depends on a context of overall cardiovascular disease risk reduction, Dr. Leong said. The results also showed a very clear, direct, linear relationship between higher BMI and both the incidence of diabetes and cardiovascular disease, as well as increased all-cause and noncardiovascular mortality among people with a BMI of less than 20 kg/m².

Dr. Yusuf discussed the results of the analysis in a video interview.

The PURE study has received partial funding from unrestricted grants from several drug companies. Dr. Leong has been an advisor to Ferring Pharmaceuticals and has been a speaker on behalf of Janssen. Dr. Yusuf had no disclosures.

[email protected]

This story was updated 9/19/2019.

PARIS – Middle-aged adults with a body mass index of 25-29 kg/m² had a significantly better adjusted survival during a median follow-up of nearly 10 years than did people with a “normal” body mass index of 20-24 kg/m² in a worldwide study of more than 140,000. This finding suggests the current, widely accepted definition of normal body mass index is wrong.*

Mitchel L. Zoler/MDedge News

The new findings suggest that the current definition of a “healthy” body mass index (BMI) “should be re-evaluated,” Darryl P. Leong, MBBS, said at the annual Congress of the European Society of Cardiology. The analysis also identified a BMI specifically of 27 kg/m² as associated with optimal survival among both women and men, “clearly outside the range of 20 to less than 25 kg/m² that is considered normal,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Dr. Leong cited three potential explanations for why the new study identified optimal survival with a BMI of 25 to less than 30 kg/m² among people who were 35-70 years old when they entered the study and were followed for a median of 9.5 years: The current study collected data and adjusted the results using a wider range of potential confounders than in prior studies, the data reflect the impact of contemporary interventions to reduce cardiovascular disease illness and death while past studies relied on data from earlier times when less cardiovascular disease protection occurred, and the current study included people from lower-income countries, although the finding is just as applicable to people who live in high-income countries, who were also included in the study population, noted Salim Yusuf, MBBS, principal investigator for the study.

A BMI of 20-24 kg/m² “is actually low and harmful,” noted Dr. Yusuf in an interview. Despite recent data consistently showing better survival among people with a BMI of 25-29 kg/m², panels that have recently written weight guidelines are “ossified” and “refuse to accept” the implications of these findings, said Dr. Yusuf, professor of medicine at McMaster and executive director of the Population Health Research Institute.

The results of the analyses that Dr. Leong reported also showed that BMI paled as a prognosticator for survival when compared with two other assessments of weight: waist/hip ratio, and even more powerful prognostically, a novel measure developed for this analysis that calculates the ratio of hand-grip strength/body weight. Waist/hip ratio adds the dimension of the location of body fat rather than just the amount, and the ratio of grip strength/body weight assesses the contribution of muscle mass to overall weight, noted Dr. Leong. He reported an optimal waist/hip ratio for survival of 0.83 in women and 0.93 in men, and an optimal strength/weight ratio of 0.42 in women and 0.50 in men. This means that a man whose hand-grip strength (measured in kg) is half of the person’s body weight has the best prospect for survival.
 
The study used data collected in PURE (Prospective Urban Rural Epidemiology Study) on 142,410 people aged 35-70 years from any one of four high-income countries, 12 middle-income countries, and five low-income countries. The study excluded people who had at baseline known coronary artery disease, stroke, heart failure, or cancer, and the adjusted analysis controlled for age, sex, region, education, activity, alcohol and tobacco use, and the baseline prevalence of hypertension and diabetes. During follow-up, 9,712 of these people died.

The researchers saw a nadir for mortality among people with a BMI of 25-29 kg/m² for both cardiovascular and noncardiovascular deaths. In addition, the link between total mortality and BMI was strongest in the subgroup of people on one or more treatments aimed at preventing cardiovascular disease, while it essentially disappeared among people not receiving any cardiovascular disease preventive measures, highlighting that the relationship now identified depends on a context of overall cardiovascular disease risk reduction, Dr. Leong said. The results also showed a very clear, direct, linear relationship between higher BMI and both the incidence of diabetes and cardiovascular disease, as well as increased all-cause and noncardiovascular mortality among people with a BMI of less than 20 kg/m².

Dr. Yusuf discussed the results of the analysis in a video interview.

The PURE study has received partial funding from unrestricted grants from several drug companies. Dr. Leong has been an advisor to Ferring Pharmaceuticals and has been a speaker on behalf of Janssen. Dr. Yusuf had no disclosures.

[email protected]

This story was updated 9/19/2019.

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

BARCELONA – Adding a blood microRNA (miRNA) assay to low-dose computed tomography (LDCT)–based lung cancer screening in heavy smokers bolsters lung cancer prevention efforts, according to findings from the prospective bioMILD trial.

Specifically, the addition of the miRNA assay appears to reduce unnecessary repeat LDCT scans based on individual risk profiles without adversely affecting lung cancer detection or mortality, Ugo Pastorino, MD, director of thoracic surgery at the Istituto Nazionale dei Tumori Foundation, Milan, reported at the World Conference on Lung Cancer.

Of 4,119 volunteers with a median age of 60 years and a median of 42 pack-years who were enrolled between January 2013 and March 2016, 2,384 (58%) were assigned a 3-year LDCT repeat according to their double-negative baseline LDCT and miRNA profile, whereas 1,526 (37%) with a single-positive screen (either a positive miRNA or indeterminate/positive LDCT) and 209 (5%) with double positive (both a positive miRNA and indeterminate/positive LDCT) were assigned to annual or shorter LDCT repeat.

After four screening runs, a total of 115 lung cancers were diagnosed. The cumulative lung cancer rates “were enormously different” in the 3 groups, despite similar group composition with respect to age, gender, and tobacco consumption (0.6% for double-negative screening, 3.8% for single-positive screening, and 20.1% for double-positive screening), and lung cancer mortality was 0.1%, 0.6%, and 3.8% in the groups, respectively, Dr. Pastorino said at the conference, which is sponsored by the International Association for the Study of Lung Cancer.

However, no significant differences were seen in the proportion of stage I lung cancers, resection rates, or interval cancer incidence in subjects sent to 3-year LDCT repeat, he noted.

The bioMILD trial was designed in the wake of the National Lung Screening Trial (NLST), which showed that three annual LDCT rounds for lung cancer screening reduced lung cancer mortality, and the Multicentric Italian Lung Detection (MILD) trial, which provided additional evidence that intervention beyond 5 years with annual or biennial rounds enhanced the benefit of screening.

Dr. Pastorino, the lead author on the MILD trial, previously reported that miRNA expression profiles in tumors and in normal lung tissue indicate aggressive lung cancer development and that specific miRNA signatures can be identified in plasma samples up to 2 years before spiral-CT detection of the disease.

The bioMILD trial tested the additional value of an miRNA assay at the time of LDCT.

Subjects were current (79%) or former heavy smokers, and 39% were women.

The findings suggest that adding the miRNA assay to LDCT for lung cancer screening is a “valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening,” Dr. Pastorino said.

“But what is more important for us [is that] the knowledge of individual biologic risk can improve the efficacy of screening, but can [also] guide prevention strategies because the problem in a heavy smoker is not to just detect lung cancer, it’s to reduce mortality,” he said at a press conference highlighting the findings. “And so, personalized prevention is a real option now, and that means diagnosis, but also preventive measures [such as] smoking cessation and chemoprevention.”

Invited discussant Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus Medical Center, Rotterdam, the Netherlands, noted that no other studies have evaluated screening intervals longer than 2 years, but he agreed that “reducing regular follow-up scans based on additional risk information is a way forward.”

However, the approach would increase costs, he said, adding that large, prospective, randomized, controlled trials are needed to confirm the safety of such approaches in nationwide programs.

Dr. Pastorino and Dr. de Koning each reported having no disclosures.

SOURCE: Pastorino U et al. WCLC 2019, Abstract PL02.04

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

[email protected]

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

[email protected]

The number of measles cases reported in the United States dropped for the fourth month in a row in August after reaching a peak of 341 in April, according to the Centers for Disease Control and Prevention.

A total of 24 measles cases were confirmed in August, and the total for the year is now 1,241 cases in 31 states. Only seven of those cases were added during the most recent reporting week, which ended Sept. 5, but five were older cases that had just been reported, the CDC said Sept. 9.

With the ending of the measles outbreak in New York, announced Sept. 3, the largest of the three remaining active outbreaks in the country is in Rockland County, N.Y., just north of the city, which has reported 312 cases since it began in 2018.

The two other outbreaks are located in El Paso, Tex., where six cases have been reported so far, and Wyoming County in western New York State, where five cases have occurred.

[email protected]

NEW YORK – The most recently approved therapy for acne, sarecycline, as well as several agents in late stages of clinical testing, might represent a particular advance for treating black patients or others with darker skin tones due to a reduced risk of irritation, according to a review presented at the Skin of Color Update 2019.

Hulldude30/Getty Images

Acne is an inflammatory skin disease, but patients with darker skin tones are at a high risk of postinflammatory hyperpigmentation (PIH), a complication many consider worse than the acne itself, according to Andrew Alexis, MD, director of the Skin of Color Center and chair of the department of dermatology at Mount Sinai St. Luke’s, New York.

“The importance of PIH is that it alters our endpoint in patients of color. Not only are we treating the pustules, comedones, and other classic features of acne, but we have to treat all the way through to the resolution of the PIH if we want a satisfied patient,” he said.

There are data to back this up. In one of the surveys cited by Dr. Alexis, 42% of nonwhite patients identified resolution of PIH as the most important goal in the treatment of their acne.

As in those with light skin, acute acne lesions in darker skin can resolve relatively rapidly after initiating an effective regimen that includes established therapies such as retinoids or antibiotics. However, PIH, once it develops, might take 6-12 months to resolve, according to Dr. Alexis, who is a professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Ted Bosworth/MDedge News

“You have to keep in mind the subclinical inflammation, which can be a slow burning process beneath the surface of the skin,” he said. He cited a biopsy study that demonstrated inflammation even in nonlesional skin of black patients with acne.

Because of the slow reversal of PIH, it is imperative in skin of color patients to employ therapies with the least risk of exacerbating PIH. While this includes judicious use of currently available agents, Dr. Alexis believes that newer agents might have a larger therapeutic window, reducing the potential for inflammation at effective doses.

This advantage has yet to be confirmed in head-to-head studies, but Dr. Alexis is optimistic. In the case of sarecycline, which became the first antibiotic approved specifically for acne when it was approved by the Food and Drug Administration in 2018, about 20% of those included in the phase 3 registration trial were nonwhite, he said.

The results were “impressive” regardless of skin color in the phase 3 study, according to Dr. Alexis. He conceded that this is not the only antibiotic with anti-inflammatory activity, but he suggested that a high degree of efficacy might be relevant for early acne control and a reduced risk of PIH.

The same can be said for trifarotene, a novel topical retinoid that was associated with highly significant reductions in both inflammatory and noninflammatory lesion counts in a recently published phase 3 trial (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9). According to Dr. Alexis, the impact of this therapy on PIH has not been specifically tested, but he expects those data to be forthcoming.

A new 0.045% lotion formulation of tazarotene might also widen the therapeutic window relative to current tazarotene formulations based on clinical trials he cited. Despite a concentration that is about half that of the currently available tazarotene cream, the efficacy of this product appeared to be at least as good “without the baggage of a greater potential for irritation,” he said.

After “a few years of drought” regarding new options for treatment of acne, these are not the only promising agents in clinical trials, according to Dr. Alexis. If these agents prove to offer greater efficacy with less irritation, their increased clinical value might prove most meaningful to patients with darker skin.

“There is a delicate balance between maximizing efficacy without causing irritation that leads to PIH in patients with skin of color,” he cautioned. He is hopeful that the newer agents will make this balance easier to achieve.

Dr. Alexis has financial relationships with many pharmaceutical companies, including many that market drugs for acne.


 

NEW YORK – The most recently approved therapy for acne, sarecycline, as well as several agents in late stages of clinical testing, might represent a particular advance for treating black patients or others with darker skin tones due to a reduced risk of irritation, according to a review presented at the Skin of Color Update 2019.

Hulldude30/Getty Images

Acne is an inflammatory skin disease, but patients with darker skin tones are at a high risk of postinflammatory hyperpigmentation (PIH), a complication many consider worse than the acne itself, according to Andrew Alexis, MD, director of the Skin of Color Center and chair of the department of dermatology at Mount Sinai St. Luke’s, New York.

“The importance of PIH is that it alters our endpoint in patients of color. Not only are we treating the pustules, comedones, and other classic features of acne, but we have to treat all the way through to the resolution of the PIH if we want a satisfied patient,” he said.

There are data to back this up. In one of the surveys cited by Dr. Alexis, 42% of nonwhite patients identified resolution of PIH as the most important goal in the treatment of their acne.

As in those with light skin, acute acne lesions in darker skin can resolve relatively rapidly after initiating an effective regimen that includes established therapies such as retinoids or antibiotics. However, PIH, once it develops, might take 6-12 months to resolve, according to Dr. Alexis, who is a professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

Ted Bosworth/MDedge News

“You have to keep in mind the subclinical inflammation, which can be a slow burning process beneath the surface of the skin,” he said. He cited a biopsy study that demonstrated inflammation even in nonlesional skin of black patients with acne.

Because of the slow reversal of PIH, it is imperative in skin of color patients to employ therapies with the least risk of exacerbating PIH. While this includes judicious use of currently available agents, Dr. Alexis believes that newer agents might have a larger therapeutic window, reducing the potential for inflammation at effective doses.

This advantage has yet to be confirmed in head-to-head studies, but Dr. Alexis is optimistic. In the case of sarecycline, which became the first antibiotic approved specifically for acne when it was approved by the Food and Drug Administration in 2018, about 20% of those included in the phase 3 registration trial were nonwhite, he said.

The results were “impressive” regardless of skin color in the phase 3 study, according to Dr. Alexis. He conceded that this is not the only antibiotic with anti-inflammatory activity, but he suggested that a high degree of efficacy might be relevant for early acne control and a reduced risk of PIH.

The same can be said for trifarotene, a novel topical retinoid that was associated with highly significant reductions in both inflammatory and noninflammatory lesion counts in a recently published phase 3 trial (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9). According to Dr. Alexis, the impact of this therapy on PIH has not been specifically tested, but he expects those data to be forthcoming.

A new 0.045% lotion formulation of tazarotene might also widen the therapeutic window relative to current tazarotene formulations based on clinical trials he cited. Despite a concentration that is about half that of the currently available tazarotene cream, the efficacy of this product appeared to be at least as good “without the baggage of a greater potential for irritation,” he said.

After “a few years of drought” regarding new options for treatment of acne, these are not the only promising agents in clinical trials, according to Dr. Alexis. If these agents prove to offer greater efficacy with less irritation, their increased clinical value might prove most meaningful to patients with darker skin.

“There is a delicate balance between maximizing efficacy without causing irritation that leads to PIH in patients with skin of color,” he cautioned. He is hopeful that the newer agents will make this balance easier to achieve.

Dr. Alexis has financial relationships with many pharmaceutical companies, including many that market drugs for acne.


 

NEW YORK – The most recently approved therapy for acne, sarecycline, as well as several agents in late stages of clinical testing, might represent a particular advance for treating black patients or others with darker skin tones due to a reduced risk of irritation, according to a review presented at the Skin of Color Update 2019.

Hulldude30/Getty Images

Acne is an inflammatory skin disease, but patients with darker skin tones are at a high risk of postinflammatory hyperpigmentation (PIH), a complication many consider worse than the acne itself, according to Andrew Alexis, MD, director of the Skin of Color Center and chair of the department of dermatology at Mount Sinai St. Luke’s, New York.

“The importance of PIH is that it alters our endpoint in patients of color. Not only are we treating the pustules, comedones, and other classic features of acne, but we have to treat all the way through to the resolution of the PIH if we want a satisfied patient,” he said.

There are data to back this up. In one of the surveys cited by Dr. Alexis, 42% of nonwhite patients identified resolution of PIH as the most important goal in the treatment of their acne.

As in those with light skin, acute acne lesions in darker skin can resolve relatively rapidly after initiating an effective regimen that includes established therapies such as retinoids or antibiotics. However, PIH, once it develops, might take 6-12 months to resolve, according to Dr. Alexis, who is a professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

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“You have to keep in mind the subclinical inflammation, which can be a slow burning process beneath the surface of the skin,” he said. He cited a biopsy study that demonstrated inflammation even in nonlesional skin of black patients with acne.

Because of the slow reversal of PIH, it is imperative in skin of color patients to employ therapies with the least risk of exacerbating PIH. While this includes judicious use of currently available agents, Dr. Alexis believes that newer agents might have a larger therapeutic window, reducing the potential for inflammation at effective doses.

This advantage has yet to be confirmed in head-to-head studies, but Dr. Alexis is optimistic. In the case of sarecycline, which became the first antibiotic approved specifically for acne when it was approved by the Food and Drug Administration in 2018, about 20% of those included in the phase 3 registration trial were nonwhite, he said.

The results were “impressive” regardless of skin color in the phase 3 study, according to Dr. Alexis. He conceded that this is not the only antibiotic with anti-inflammatory activity, but he suggested that a high degree of efficacy might be relevant for early acne control and a reduced risk of PIH.

The same can be said for trifarotene, a novel topical retinoid that was associated with highly significant reductions in both inflammatory and noninflammatory lesion counts in a recently published phase 3 trial (J Am Acad Dermatol. 2019 Jun;80[6]:1691-9). According to Dr. Alexis, the impact of this therapy on PIH has not been specifically tested, but he expects those data to be forthcoming.

A new 0.045% lotion formulation of tazarotene might also widen the therapeutic window relative to current tazarotene formulations based on clinical trials he cited. Despite a concentration that is about half that of the currently available tazarotene cream, the efficacy of this product appeared to be at least as good “without the baggage of a greater potential for irritation,” he said.

After “a few years of drought” regarding new options for treatment of acne, these are not the only promising agents in clinical trials, according to Dr. Alexis. If these agents prove to offer greater efficacy with less irritation, their increased clinical value might prove most meaningful to patients with darker skin.

“There is a delicate balance between maximizing efficacy without causing irritation that leads to PIH in patients with skin of color,” he cautioned. He is hopeful that the newer agents will make this balance easier to achieve.

Dr. Alexis has financial relationships with many pharmaceutical companies, including many that market drugs for acne.