There is little doubt that the psychopharmacology revolution has been transformational for psychiatry and is also credited for sparking the momentous neuroscience advances of the past half century.

The field of psychiatry, dominated by Freudian psychology for decades, radically evolved from psychoanalysis to pharmacotherapy with the discovery that serious mental disorders are treatable with medications, thus dispensing with the couch.

Prior to 1952, the prevailing dogma was that “madness is irreversible.” That’s why millions of patients with various psychiatric disorders were locked up in institutions, which added to the stigma of mental illness. Then came the first antipsychotic drug, chlorpromazine, which “magically” eliminated the delusions and hallucinations of patients who had been hospitalized for years. That serendipitous and historic discovery was as transformational for psychiatry as penicillin was for infections (yet inexplicably, only the discovery of penicillin received a Nobel Prize). Most people today do not know that before chlorpromazine, 50% of all hospital beds in the U.S. were occupied by psychiatric patients. The massive shuttering of state hospitals in the 1970s and ’80s was a direct consequence of the widespread use of chlorpromazine and its cohort of first-generation antipsychotics (FGAs).

That was Psychopharmacology 1.0, spanning the period 1952 to 1987. It included dozens of FGAs belonging to 6 classes: phenothiazines, thioxanthenes, butyrophenones, dibenzazepines, dihydroindolones, and dibenzodiazepines. Psychopharmacology 1.0 also included monoamine oxidase inhibitors and tricyclic antidepressants for depression, and lithium for bipolar mania. Ironically, clozapine, the incognito seed template of the second-generation antipsychotic (SGA) class, was synthesized in 1959 with the early wave of FGAs, and launched in Europe in 1972, only to be withdrawn in 1974 due to agranulocytosis-induced deaths not recognized during the clinical trials.

The late 1980s ushered in Psychopharmacology 2.0, which was also transformative. It began in 1987 with the introduction of fluoxetine, the first selective serotonin receptor inhibitor. Then clozapine was resurrected in 1988 as the first FDA-approved drug for refractory schizophrenia. Being the first SGA (no acute extrapyramidal side effects at all, in contrast to all FGAs), it became the “mechanistic model” for all other SGA agents, which were introduced starting in 1993. All SGAs were designed by pharmaceutical companies’ medicinal chemists to mimic clozapine’s receptor profile: far stronger affinity to serotonin 5HT-2A receptors than to dopamine D2 receptors. Three partial agonists and several heterocyclic antidepressants were also introduced during this 2.0 era, which continued until approximately 2017. Of the 11 SGAs that were initially approved for schizophrenia, 7 also were approved for bipolar mania, and 2 received an FDA indication for bipolar depression, thus addressing a glaring unmet need.

Psychopharmacology 3.0 has already begun. Its seeds started sprouting over the past few years with the landmark studies of intravenous ketamine, which was demonstrated to reverse severe and refractory depression and suicidal urges within hours of injection. The first ketamine product, esketamine, an intranasal formulation, is expected to be approved by the FDA soon. In the same vein, other rapid-acting antidepressants, a welcome paradigm shift, are being developed, including IV scopolamine, IV rapastinel, and inhalable nitrous oxide.

Three novel and important pharmacologic agents have arrived in this 3.0 era:

• Pimavanserin, a serotonin 5HT-2A inverse agonist, the first and only non-dopamine–blocking antipsychotic approved by the FDA for the delusions and hallucinations of Parkinson’s disease psychosis. It is currently in clinical trials for schizophrenia and Alzheimer’s disease psychosis (for which nothing is yet approved).
• Valbenazine, the first drug approved for tardive dyskinesia (TD), the treatment of which had been elusive and remained a huge unmet need for 60 years. Its novel mechanism of action is inhibition of vesicular monoamine transporter 2 (VMAT2), which reduces the putative dopamine supersensitivity of TD.
• Deutetrabenazine, which was also approved for TD a few months after valbenazine, and has the same mechanism of action. It also was approved for Huntington’s chorea.

Continue to: Another important feature...

Another important feature of Psychopharmacology 3.0 is the repurposing of hallucinogens into novel therapies for posttraumatic stress disorder, anxiety, and depression.¹ The opioid system is being recognized as another key player in depression, with many studies showing buprenorphine has antidepressant and anti-suicidal properties² and the recent finding that pre-treatment with naloxone blocks the rapid antidepressive effects of ketamine.³ This finding casts doubt on the notion that the antidepressant mechanism of action of ketamine is solely mediated via its antagonism of the glutamate N-methyl-D-aspartate (NMDA) receptor. Another imminent innovative antidepressant mechanism of action is represented by brexanolone, an allosteric modulator of GABA-A receptors (which are known to become dormant during pregnancy and are not reactivated after delivery in women who develop postpartum depression).

These early developments in Psychopharmacology 3.0 augur well for the future. Companies in the pharmaceutical industry (which are hated by many, and even demonized and kept at arm’s length by major medical schools) are, in fact, the only entities in the world that develop new medications for psychiatric disorders, 82% of which still have no FDA-approved drug.⁴ Psychiatric researchers and clinicians should collaborate and advise the pharmaceutical companies about the urgent or unmet needs of psychiatric patients so they can target those unmet needs with their massive R&D resources.

In that spirit, here is my wish list of therapeutic targets that I hope will emerge during the Psychopharmacology 3.0 era and beyond:

1. New mechanisms of action for antipsychotics, based on emerging neurobiological research in schizophrenia and related psychoses, such as:

• Inhibit microglia activation
• Repair mitochondrial dysfunction
• Modulate the hypofunctional NMDA receptors
• Inhibit apoptosis
• Enhance neurogenesis
• Repair myelin pathology
• Inhibit neuroinflammation and oxidative stress
• Increase neurotropic growth factors
• Neurosteroid therapies (including estrogen)
• Exploit the microbiome influence on both the enteric and cephalic brains

2. Long-acting injectable antidepressants and mood stabilizers, because there is a malignant transformation into treatment-resistance in mood disorders after recurrent episodes due to nonadherence.⁵

3. Treatments for personality disorders, especially borderline and antisocial personality disorders.

4. An effective treatment for alcoholism.

5. Pharmacotherapy for aggression.

6. Vaccines for substance use.

7. Stage-specific pharmacotherapies (because the neurobiology of prodromal, first-episode, and multiple-episode patients have been shown to be quite different).

8. Drugs for epigenetic modulation to inhibit risk genes and to over-express protective genes.

It may take decades and hundreds of billions (even trillions) of R&D investment to accomplish the above, but I remain excited about the prospects of astounding psychopharmacologic advances to treat the disorders of the mind. Precision psychiatry advances will also expedite the selection of the right medication for each patient by employing predictive biomarkers. Breakthrough methodologies, such as pluripotent stem cells, opto-genetics, and clustered regularly interspaced short palindromic repeats (CRISPR), promise to revolutionize the biology, diagnosis, treatment, and prevention of various neuropsychiatric disorders.

The future of psychopharmacology is bright, if adequate resources are invested. The current direct and indirect costs of mental disorders and addictions are in the hundreds of billions of dollars annually. Only intensive research and disruptive discoveries will have the salutary dual effect of healing disease and reducing the economic burden of neuropsychiatric disorders. Psychopharmacology 3.0 advances, along with nonpharmacologic therapies such as neuromodulation (electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation, and a dozen other techniques in development). Together with the indispensable evidence-based psychotherapies such as cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal psychotherapy, psychopharmacology represents the leading edge of progress in psychiatric treatment. The psychiatrists of 1952 could only fantasize about what has since become a reality in healing ailing minds.

To comment on this editorial or other topics of interest: [email protected]

There is little doubt that the psychopharmacology revolution has been transformational for psychiatry and is also credited for sparking the momentous neuroscience advances of the past half century.

The field of psychiatry, dominated by Freudian psychology for decades, radically evolved from psychoanalysis to pharmacotherapy with the discovery that serious mental disorders are treatable with medications, thus dispensing with the couch.

Prior to 1952, the prevailing dogma was that “madness is irreversible.” That’s why millions of patients with various psychiatric disorders were locked up in institutions, which added to the stigma of mental illness. Then came the first antipsychotic drug, chlorpromazine, which “magically” eliminated the delusions and hallucinations of patients who had been hospitalized for years. That serendipitous and historic discovery was as transformational for psychiatry as penicillin was for infections (yet inexplicably, only the discovery of penicillin received a Nobel Prize). Most people today do not know that before chlorpromazine, 50% of all hospital beds in the U.S. were occupied by psychiatric patients. The massive shuttering of state hospitals in the 1970s and ’80s was a direct consequence of the widespread use of chlorpromazine and its cohort of first-generation antipsychotics (FGAs).

That was Psychopharmacology 1.0, spanning the period 1952 to 1987. It included dozens of FGAs belonging to 6 classes: phenothiazines, thioxanthenes, butyrophenones, dibenzazepines, dihydroindolones, and dibenzodiazepines. Psychopharmacology 1.0 also included monoamine oxidase inhibitors and tricyclic antidepressants for depression, and lithium for bipolar mania. Ironically, clozapine, the incognito seed template of the second-generation antipsychotic (SGA) class, was synthesized in 1959 with the early wave of FGAs, and launched in Europe in 1972, only to be withdrawn in 1974 due to agranulocytosis-induced deaths not recognized during the clinical trials.

The late 1980s ushered in Psychopharmacology 2.0, which was also transformative. It began in 1987 with the introduction of fluoxetine, the first selective serotonin receptor inhibitor. Then clozapine was resurrected in 1988 as the first FDA-approved drug for refractory schizophrenia. Being the first SGA (no acute extrapyramidal side effects at all, in contrast to all FGAs), it became the “mechanistic model” for all other SGA agents, which were introduced starting in 1993. All SGAs were designed by pharmaceutical companies’ medicinal chemists to mimic clozapine’s receptor profile: far stronger affinity to serotonin 5HT-2A receptors than to dopamine D2 receptors. Three partial agonists and several heterocyclic antidepressants were also introduced during this 2.0 era, which continued until approximately 2017. Of the 11 SGAs that were initially approved for schizophrenia, 7 also were approved for bipolar mania, and 2 received an FDA indication for bipolar depression, thus addressing a glaring unmet need.

Psychopharmacology 3.0 has already begun. Its seeds started sprouting over the past few years with the landmark studies of intravenous ketamine, which was demonstrated to reverse severe and refractory depression and suicidal urges within hours of injection. The first ketamine product, esketamine, an intranasal formulation, is expected to be approved by the FDA soon. In the same vein, other rapid-acting antidepressants, a welcome paradigm shift, are being developed, including IV scopolamine, IV rapastinel, and inhalable nitrous oxide.

Three novel and important pharmacologic agents have arrived in this 3.0 era:

• Pimavanserin, a serotonin 5HT-2A inverse agonist, the first and only non-dopamine–blocking antipsychotic approved by the FDA for the delusions and hallucinations of Parkinson’s disease psychosis. It is currently in clinical trials for schizophrenia and Alzheimer’s disease psychosis (for which nothing is yet approved).
• Valbenazine, the first drug approved for tardive dyskinesia (TD), the treatment of which had been elusive and remained a huge unmet need for 60 years. Its novel mechanism of action is inhibition of vesicular monoamine transporter 2 (VMAT2), which reduces the putative dopamine supersensitivity of TD.
• Deutetrabenazine, which was also approved for TD a few months after valbenazine, and has the same mechanism of action. It also was approved for Huntington’s chorea.

Continue to: Another important feature...

Another important feature of Psychopharmacology 3.0 is the repurposing of hallucinogens into novel therapies for posttraumatic stress disorder, anxiety, and depression.¹ The opioid system is being recognized as another key player in depression, with many studies showing buprenorphine has antidepressant and anti-suicidal properties² and the recent finding that pre-treatment with naloxone blocks the rapid antidepressive effects of ketamine.³ This finding casts doubt on the notion that the antidepressant mechanism of action of ketamine is solely mediated via its antagonism of the glutamate N-methyl-D-aspartate (NMDA) receptor. Another imminent innovative antidepressant mechanism of action is represented by brexanolone, an allosteric modulator of GABA-A receptors (which are known to become dormant during pregnancy and are not reactivated after delivery in women who develop postpartum depression).

These early developments in Psychopharmacology 3.0 augur well for the future. Companies in the pharmaceutical industry (which are hated by many, and even demonized and kept at arm’s length by major medical schools) are, in fact, the only entities in the world that develop new medications for psychiatric disorders, 82% of which still have no FDA-approved drug.⁴ Psychiatric researchers and clinicians should collaborate and advise the pharmaceutical companies about the urgent or unmet needs of psychiatric patients so they can target those unmet needs with their massive R&D resources.

In that spirit, here is my wish list of therapeutic targets that I hope will emerge during the Psychopharmacology 3.0 era and beyond:

1. New mechanisms of action for antipsychotics, based on emerging neurobiological research in schizophrenia and related psychoses, such as:

• Inhibit microglia activation
• Repair mitochondrial dysfunction
• Modulate the hypofunctional NMDA receptors
• Inhibit apoptosis
• Enhance neurogenesis
• Repair myelin pathology
• Inhibit neuroinflammation and oxidative stress
• Increase neurotropic growth factors
• Neurosteroid therapies (including estrogen)
• Exploit the microbiome influence on both the enteric and cephalic brains

2. Long-acting injectable antidepressants and mood stabilizers, because there is a malignant transformation into treatment-resistance in mood disorders after recurrent episodes due to nonadherence.⁵

3. Treatments for personality disorders, especially borderline and antisocial personality disorders.

4. An effective treatment for alcoholism.

5. Pharmacotherapy for aggression.

6. Vaccines for substance use.

7. Stage-specific pharmacotherapies (because the neurobiology of prodromal, first-episode, and multiple-episode patients have been shown to be quite different).

8. Drugs for epigenetic modulation to inhibit risk genes and to over-express protective genes.

It may take decades and hundreds of billions (even trillions) of R&D investment to accomplish the above, but I remain excited about the prospects of astounding psychopharmacologic advances to treat the disorders of the mind. Precision psychiatry advances will also expedite the selection of the right medication for each patient by employing predictive biomarkers. Breakthrough methodologies, such as pluripotent stem cells, opto-genetics, and clustered regularly interspaced short palindromic repeats (CRISPR), promise to revolutionize the biology, diagnosis, treatment, and prevention of various neuropsychiatric disorders.

The future of psychopharmacology is bright, if adequate resources are invested. The current direct and indirect costs of mental disorders and addictions are in the hundreds of billions of dollars annually. Only intensive research and disruptive discoveries will have the salutary dual effect of healing disease and reducing the economic burden of neuropsychiatric disorders. Psychopharmacology 3.0 advances, along with nonpharmacologic therapies such as neuromodulation (electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation, and a dozen other techniques in development). Together with the indispensable evidence-based psychotherapies such as cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal psychotherapy, psychopharmacology represents the leading edge of progress in psychiatric treatment. The psychiatrists of 1952 could only fantasize about what has since become a reality in healing ailing minds.

To comment on this editorial or other topics of interest: [email protected]

There is little doubt that the psychopharmacology revolution has been transformational for psychiatry and is also credited for sparking the momentous neuroscience advances of the past half century.

The field of psychiatry, dominated by Freudian psychology for decades, radically evolved from psychoanalysis to pharmacotherapy with the discovery that serious mental disorders are treatable with medications, thus dispensing with the couch.

Prior to 1952, the prevailing dogma was that “madness is irreversible.” That’s why millions of patients with various psychiatric disorders were locked up in institutions, which added to the stigma of mental illness. Then came the first antipsychotic drug, chlorpromazine, which “magically” eliminated the delusions and hallucinations of patients who had been hospitalized for years. That serendipitous and historic discovery was as transformational for psychiatry as penicillin was for infections (yet inexplicably, only the discovery of penicillin received a Nobel Prize). Most people today do not know that before chlorpromazine, 50% of all hospital beds in the U.S. were occupied by psychiatric patients. The massive shuttering of state hospitals in the 1970s and ’80s was a direct consequence of the widespread use of chlorpromazine and its cohort of first-generation antipsychotics (FGAs).

That was Psychopharmacology 1.0, spanning the period 1952 to 1987. It included dozens of FGAs belonging to 6 classes: phenothiazines, thioxanthenes, butyrophenones, dibenzazepines, dihydroindolones, and dibenzodiazepines. Psychopharmacology 1.0 also included monoamine oxidase inhibitors and tricyclic antidepressants for depression, and lithium for bipolar mania. Ironically, clozapine, the incognito seed template of the second-generation antipsychotic (SGA) class, was synthesized in 1959 with the early wave of FGAs, and launched in Europe in 1972, only to be withdrawn in 1974 due to agranulocytosis-induced deaths not recognized during the clinical trials.

The late 1980s ushered in Psychopharmacology 2.0, which was also transformative. It began in 1987 with the introduction of fluoxetine, the first selective serotonin receptor inhibitor. Then clozapine was resurrected in 1988 as the first FDA-approved drug for refractory schizophrenia. Being the first SGA (no acute extrapyramidal side effects at all, in contrast to all FGAs), it became the “mechanistic model” for all other SGA agents, which were introduced starting in 1993. All SGAs were designed by pharmaceutical companies’ medicinal chemists to mimic clozapine’s receptor profile: far stronger affinity to serotonin 5HT-2A receptors than to dopamine D2 receptors. Three partial agonists and several heterocyclic antidepressants were also introduced during this 2.0 era, which continued until approximately 2017. Of the 11 SGAs that were initially approved for schizophrenia, 7 also were approved for bipolar mania, and 2 received an FDA indication for bipolar depression, thus addressing a glaring unmet need.

Psychopharmacology 3.0 has already begun. Its seeds started sprouting over the past few years with the landmark studies of intravenous ketamine, which was demonstrated to reverse severe and refractory depression and suicidal urges within hours of injection. The first ketamine product, esketamine, an intranasal formulation, is expected to be approved by the FDA soon. In the same vein, other rapid-acting antidepressants, a welcome paradigm shift, are being developed, including IV scopolamine, IV rapastinel, and inhalable nitrous oxide.

Three novel and important pharmacologic agents have arrived in this 3.0 era:

• Pimavanserin, a serotonin 5HT-2A inverse agonist, the first and only non-dopamine–blocking antipsychotic approved by the FDA for the delusions and hallucinations of Parkinson’s disease psychosis. It is currently in clinical trials for schizophrenia and Alzheimer’s disease psychosis (for which nothing is yet approved).
• Valbenazine, the first drug approved for tardive dyskinesia (TD), the treatment of which had been elusive and remained a huge unmet need for 60 years. Its novel mechanism of action is inhibition of vesicular monoamine transporter 2 (VMAT2), which reduces the putative dopamine supersensitivity of TD.
• Deutetrabenazine, which was also approved for TD a few months after valbenazine, and has the same mechanism of action. It also was approved for Huntington’s chorea.

Continue to: Another important feature...

Another important feature of Psychopharmacology 3.0 is the repurposing of hallucinogens into novel therapies for posttraumatic stress disorder, anxiety, and depression.¹ The opioid system is being recognized as another key player in depression, with many studies showing buprenorphine has antidepressant and anti-suicidal properties² and the recent finding that pre-treatment with naloxone blocks the rapid antidepressive effects of ketamine.³ This finding casts doubt on the notion that the antidepressant mechanism of action of ketamine is solely mediated via its antagonism of the glutamate N-methyl-D-aspartate (NMDA) receptor. Another imminent innovative antidepressant mechanism of action is represented by brexanolone, an allosteric modulator of GABA-A receptors (which are known to become dormant during pregnancy and are not reactivated after delivery in women who develop postpartum depression).

These early developments in Psychopharmacology 3.0 augur well for the future. Companies in the pharmaceutical industry (which are hated by many, and even demonized and kept at arm’s length by major medical schools) are, in fact, the only entities in the world that develop new medications for psychiatric disorders, 82% of which still have no FDA-approved drug.⁴ Psychiatric researchers and clinicians should collaborate and advise the pharmaceutical companies about the urgent or unmet needs of psychiatric patients so they can target those unmet needs with their massive R&D resources.

In that spirit, here is my wish list of therapeutic targets that I hope will emerge during the Psychopharmacology 3.0 era and beyond:

1. New mechanisms of action for antipsychotics, based on emerging neurobiological research in schizophrenia and related psychoses, such as:

• Inhibit microglia activation
• Repair mitochondrial dysfunction
• Modulate the hypofunctional NMDA receptors
• Inhibit apoptosis
• Enhance neurogenesis
• Repair myelin pathology
• Inhibit neuroinflammation and oxidative stress
• Increase neurotropic growth factors
• Neurosteroid therapies (including estrogen)
• Exploit the microbiome influence on both the enteric and cephalic brains

2. Long-acting injectable antidepressants and mood stabilizers, because there is a malignant transformation into treatment-resistance in mood disorders after recurrent episodes due to nonadherence.⁵

3. Treatments for personality disorders, especially borderline and antisocial personality disorders.

4. An effective treatment for alcoholism.

5. Pharmacotherapy for aggression.

6. Vaccines for substance use.

7. Stage-specific pharmacotherapies (because the neurobiology of prodromal, first-episode, and multiple-episode patients have been shown to be quite different).

8. Drugs for epigenetic modulation to inhibit risk genes and to over-express protective genes.

It may take decades and hundreds of billions (even trillions) of R&D investment to accomplish the above, but I remain excited about the prospects of astounding psychopharmacologic advances to treat the disorders of the mind. Precision psychiatry advances will also expedite the selection of the right medication for each patient by employing predictive biomarkers. Breakthrough methodologies, such as pluripotent stem cells, opto-genetics, and clustered regularly interspaced short palindromic repeats (CRISPR), promise to revolutionize the biology, diagnosis, treatment, and prevention of various neuropsychiatric disorders.

The future of psychopharmacology is bright, if adequate resources are invested. The current direct and indirect costs of mental disorders and addictions are in the hundreds of billions of dollars annually. Only intensive research and disruptive discoveries will have the salutary dual effect of healing disease and reducing the economic burden of neuropsychiatric disorders. Psychopharmacology 3.0 advances, along with nonpharmacologic therapies such as neuromodulation (electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation, and a dozen other techniques in development). Together with the indispensable evidence-based psychotherapies such as cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal psychotherapy, psychopharmacology represents the leading edge of progress in psychiatric treatment. The psychiatrists of 1952 could only fantasize about what has since become a reality in healing ailing minds.

To comment on this editorial or other topics of interest: [email protected]

BERLIN—Applying the 2017 McDonald criteria to children is feasible and allows an earlier diagnosis of multiple sclerosis (MS), according to data described at ECTRIMS 2018. The presence of oligoclonal bands and negativity of myelin oligodendrocyte glycoprotein (MOG)-IgG are informative biomarkers when evaluating the risk of MS in children with a first demyelinating event, said the authors.

Few researchers have examined the application of the revised 2017 McDonald criteria to children. In addition, the role of biomarkers in confirming or ruling out a diagnosis of MS is uncertain. Georgina Arrambide, MD, PhD, a neurologist at Vall d’Hebron University Hospital in Barcelona, and colleagues conducted a prospective cohort study to compare the application of the 2017 and 2010 McDonald criteria in children with a first demyelinating event and to evaluate the contribution of biomarkers (ie, oligoclonal bands, aquaporin 4 [AQP4], and MOG-IgG) in predicting their clinical course.

BERLIN—Applying the 2017 McDonald criteria to children is feasible and allows an earlier diagnosis of multiple sclerosis (MS), according to data described at ECTRIMS 2018. The presence of oligoclonal bands and negativity of myelin oligodendrocyte glycoprotein (MOG)-IgG are informative biomarkers when evaluating the risk of MS in children with a first demyelinating event, said the authors.

Few researchers have examined the application of the revised 2017 McDonald criteria to children. In addition, the role of biomarkers in confirming or ruling out a diagnosis of MS is uncertain. Georgina Arrambide, MD, PhD, a neurologist at Vall d’Hebron University Hospital in Barcelona, and colleagues conducted a prospective cohort study to compare the application of the 2017 and 2010 McDonald criteria in children with a first demyelinating event and to evaluate the contribution of biomarkers (ie, oligoclonal bands, aquaporin 4 [AQP4], and MOG-IgG) in predicting their clinical course.

BERLIN—Applying the 2017 McDonald criteria to children is feasible and allows an earlier diagnosis of multiple sclerosis (MS), according to data described at ECTRIMS 2018. The presence of oligoclonal bands and negativity of myelin oligodendrocyte glycoprotein (MOG)-IgG are informative biomarkers when evaluating the risk of MS in children with a first demyelinating event, said the authors.

Few researchers have examined the application of the revised 2017 McDonald criteria to children. In addition, the role of biomarkers in confirming or ruling out a diagnosis of MS is uncertain. Georgina Arrambide, MD, PhD, a neurologist at Vall d’Hebron University Hospital in Barcelona, and colleagues conducted a prospective cohort study to compare the application of the 2017 and 2010 McDonald criteria in children with a first demyelinating event and to evaluate the contribution of biomarkers (ie, oligoclonal bands, aquaporin 4 [AQP4], and MOG-IgG) in predicting their clinical course.

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Vaginal and bilateral thigh removal of a transobturator sling
• Morcellation at the time of vaginal hysterectomy
• Surgical management of non-tubal ectopic pregnancies

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Vaginal and bilateral thigh removal of a transobturator sling
• Morcellation at the time of vaginal hysterectomy
• Surgical management of non-tubal ectopic pregnancies

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Vaginal and bilateral thigh removal of a transobturator sling
• Morcellation at the time of vaginal hysterectomy
• Surgical management of non-tubal ectopic pregnancies

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

MUNICH – In patients with recurrent or metastatic head and neck squamous cell carcinoma expressing programmed death ligand-1 (PDL-1), the immune checkpoint inhibitor pembrolizumab alone or in combination with chemotherapy improved overall survival, compared with the EXTREME chemotherapy regimen, reported investigators in the Keynote 048 trial.

Neil Osterweil/MDedge News

Overall survival (OS) among patients with a PD-L1 combined positive score (CPS) of 20 or greater treated with pembrolizumab (Keytruda) monotherapy was 14.9 months compared with 10.7 months for patients treated with the EXTREME regimen, a combination of cetuximab (Erbitux), carboplatin or cisplatin, and 5-fluorouracil.

A similar overall survival benefit was seen in patients with a CPS of 1 or greater, and in the total population of patients treated with pembrolizumab plus chemotherapy followed by pembrolizumab maintenance compared with EXTREME chemotherapy, Barbara Burtness, MD, of Yale Cancer Center, New Haven, Conn.

There were no differences in response rates between either pembrolizumab monotherapy or in combination compared with chemotherapy alone, but responses were more durable with the checkpoint inhibitor than with chemotherapy.

“Pembrolizumab alone and pembrolizumab given with platinum and 5-fluorouracil should represent new standards of care for the first-line treatment of metastatic head and neck carcinoma. Immune checkpoint monotherapy with pembrolizumab allows patients to live longer and has a better safety profile than the previous standard for those patients whose tumors express PD-L1,” she said at a briefing prior to her presentation of the data in a presidential symposium at the European Society for Medical Oncology Congress.

“This is the first time since 10 years that we show an improvement in survival for this group of patients,” said Jean-Pascal Machiels, MD, of University Clinic Saint-Luc, Brussels, the invited discussant for the briefing and the symposium.

The CPS is a ratio of PD-L1-positive tumor cells, lymphocytes, and macrophages to the total numbers of cells counted multiplied by 100. The investigators looked at progression-free survival (PFS) and OS in three cohorts of patients with squamous cell carcinomas of the oropharynx, oral cavity, hypopharynx, or larynx that were recurrent or metastatic and were incurable by local therapies. They compared pembrolizumab monotherapy with the EXTREME regimen, and pembrolizumab plus chemotherapy (as described in the following paragraph) with EXTREME.

A total of 882 patients were enrolled and stratified by PD-L1 expression (on 50% or greater of tumor cells, or less than 50%), p16 positive or negative status in the oropharynx, and Eastern Cooperative Oncology Group performance status of 0 or 1. The patients were then randomly assigned on a 1:1:1 basis to either pembrolizumab monotherapy at 200 mg every 3 weeks for up to 35 cycles, pembrolizumab plus a standard chemotherapy regimen (carboplatin to an area-under-the curve [AUC] of 5 or cisplatin 100 mg/m² plus 5-FU 1000 mg/m2 ^per day for 4 days for six cycles, followed by pembrolizumab maintenance for up to 35 cycles or EXTREME (cetuximab at a loading dose of 400 mg/m² followed by 250 mg/m² once weekly plus the chemotherapy regimen described above, followed by maintenance cetuximab).
 

Pembrolizumab monotherapy vs. EXTREME

For the coprimary endpoint of OS in the CPS 20 or greater population, pembrolizumab was associated with significantly better survival than EXTREME at both the 12- and 24-month time points (56.9% vs. 44.9%, and 38.3% vs. 22,1%, respectively). After a minimum follow-up of 17 months, the median OS was 14.9 months with pembrolizumab, vs. 10.7 months for EXTREME. The hazard ratio (HR) for death with pembrolizumab was 0.61 (P = .0007).

The median OS in the CPS 1 or greater population was 12.3 months and 10.3 months, respectively (HR 0.78, P = .0086).

There were no differences between the arms in PFS, however, either in the CPS 20 or greater or CPS 1 or greater populations.

Although, as noted, response rates did not differ between the groups, the median duration of response was 20.9 months with pembrolizumab in both the CPS 20 and CPS 1 populations, compared with 4.2 and 4.5 months, respectively, for EXTREME.

Treatment-related adverse events of any grade occurred in 58% of patients in the monotherapy arm, vs. 96.9% in the EXTREME arm. Fatal adverse events occurred in 1% vs. 2.8%, and events leading to drug discontinuation occurred in 4.7% vs. 19.9%, respectively. There were more immune-mediated events in the pembrolizumab arm, including one death (from pneumonitis) vs. no deaths from immune-related causes in the EXTREME arm.
 

Pembrolizumab plus chemo vs. EXTREME

The combination of pembrolizumab was also superior to EXTREME in the total population, with 12- and 24-month OS rates of 53% vs. 43.9%, and 29% vs. 18.7%, respectively. The median OS was 13 months with the pembrolizumab/chemo combination, vs. 10.7 months for EXTREME, translating into an HR of 0.77 (P = .0034). In this analysis as well as in the pembrolizumab monotherapy combination, there was no difference in PFS or response rates, but responses in the pembrolizumab arm were more durable.

In this comparison, treatment-related adverse events were generally similar between the groups, although there were 10 treatment-related deaths with pembrolizumab, compared with eight in the EXTREME arm.

There was one immune-related death, from pneumonitis, in the pembrolizumab arm, vs. none in the EXTREME arm. Hypothyroidism, pneumonitis, hyperthyroidism and colitis were more frequent with pembrolizumab, whereas infusion reactions and severe skin reactions were more frequent with EXTREME.

“There are further analyses of biomarker and clinical predictors that will be forthcoming from this study, and these may eventually optimally guide the choice of whether to administer pembrolizumab alone or in the novel combination, Dr. Burtness said at the briefing.

“What’s extremely important also is that for a subgroup of patients with high expression of PD-L1, we can probably remove the cisplatin and have a good outcome with immunotherapy alone,” Dr. Machiels said.

He said that more work needs to be done to determine which patients are most likely to benefit from immunotherapy in the recurrent/metastatic setting, and “we have to see how we can now bring this active drug to the curative treatment of the patient, in combination with chemoradiation.”

The study was funded by Merck Sharp & Dohme. Dr. Burtness disclosed being and advisory board member and receiving travel expenses from MSD and others. Dr. Machiels disclosed speaker honoraria, travel expenses, and an uncompensated advisory role with MSD.

SOURCE: Burtness B et al. ESMO 2018. Abstract LBA8_PR.

MUNICH – In patients with recurrent or metastatic head and neck squamous cell carcinoma expressing programmed death ligand-1 (PDL-1), the immune checkpoint inhibitor pembrolizumab alone or in combination with chemotherapy improved overall survival, compared with the EXTREME chemotherapy regimen, reported investigators in the Keynote 048 trial.

Neil Osterweil/MDedge News

Overall survival (OS) among patients with a PD-L1 combined positive score (CPS) of 20 or greater treated with pembrolizumab (Keytruda) monotherapy was 14.9 months compared with 10.7 months for patients treated with the EXTREME regimen, a combination of cetuximab (Erbitux), carboplatin or cisplatin, and 5-fluorouracil.

A similar overall survival benefit was seen in patients with a CPS of 1 or greater, and in the total population of patients treated with pembrolizumab plus chemotherapy followed by pembrolizumab maintenance compared with EXTREME chemotherapy, Barbara Burtness, MD, of Yale Cancer Center, New Haven, Conn.

There were no differences in response rates between either pembrolizumab monotherapy or in combination compared with chemotherapy alone, but responses were more durable with the checkpoint inhibitor than with chemotherapy.

“Pembrolizumab alone and pembrolizumab given with platinum and 5-fluorouracil should represent new standards of care for the first-line treatment of metastatic head and neck carcinoma. Immune checkpoint monotherapy with pembrolizumab allows patients to live longer and has a better safety profile than the previous standard for those patients whose tumors express PD-L1,” she said at a briefing prior to her presentation of the data in a presidential symposium at the European Society for Medical Oncology Congress.

“This is the first time since 10 years that we show an improvement in survival for this group of patients,” said Jean-Pascal Machiels, MD, of University Clinic Saint-Luc, Brussels, the invited discussant for the briefing and the symposium.

The CPS is a ratio of PD-L1-positive tumor cells, lymphocytes, and macrophages to the total numbers of cells counted multiplied by 100. The investigators looked at progression-free survival (PFS) and OS in three cohorts of patients with squamous cell carcinomas of the oropharynx, oral cavity, hypopharynx, or larynx that were recurrent or metastatic and were incurable by local therapies. They compared pembrolizumab monotherapy with the EXTREME regimen, and pembrolizumab plus chemotherapy (as described in the following paragraph) with EXTREME.

A total of 882 patients were enrolled and stratified by PD-L1 expression (on 50% or greater of tumor cells, or less than 50%), p16 positive or negative status in the oropharynx, and Eastern Cooperative Oncology Group performance status of 0 or 1. The patients were then randomly assigned on a 1:1:1 basis to either pembrolizumab monotherapy at 200 mg every 3 weeks for up to 35 cycles, pembrolizumab plus a standard chemotherapy regimen (carboplatin to an area-under-the curve [AUC] of 5 or cisplatin 100 mg/m² plus 5-FU 1000 mg/m2 ^per day for 4 days for six cycles, followed by pembrolizumab maintenance for up to 35 cycles or EXTREME (cetuximab at a loading dose of 400 mg/m² followed by 250 mg/m² once weekly plus the chemotherapy regimen described above, followed by maintenance cetuximab).
 

Pembrolizumab monotherapy vs. EXTREME

For the coprimary endpoint of OS in the CPS 20 or greater population, pembrolizumab was associated with significantly better survival than EXTREME at both the 12- and 24-month time points (56.9% vs. 44.9%, and 38.3% vs. 22,1%, respectively). After a minimum follow-up of 17 months, the median OS was 14.9 months with pembrolizumab, vs. 10.7 months for EXTREME. The hazard ratio (HR) for death with pembrolizumab was 0.61 (P = .0007).

The median OS in the CPS 1 or greater population was 12.3 months and 10.3 months, respectively (HR 0.78, P = .0086).

There were no differences between the arms in PFS, however, either in the CPS 20 or greater or CPS 1 or greater populations.

Although, as noted, response rates did not differ between the groups, the median duration of response was 20.9 months with pembrolizumab in both the CPS 20 and CPS 1 populations, compared with 4.2 and 4.5 months, respectively, for EXTREME.

Treatment-related adverse events of any grade occurred in 58% of patients in the monotherapy arm, vs. 96.9% in the EXTREME arm. Fatal adverse events occurred in 1% vs. 2.8%, and events leading to drug discontinuation occurred in 4.7% vs. 19.9%, respectively. There were more immune-mediated events in the pembrolizumab arm, including one death (from pneumonitis) vs. no deaths from immune-related causes in the EXTREME arm.
 

Pembrolizumab plus chemo vs. EXTREME

The combination of pembrolizumab was also superior to EXTREME in the total population, with 12- and 24-month OS rates of 53% vs. 43.9%, and 29% vs. 18.7%, respectively. The median OS was 13 months with the pembrolizumab/chemo combination, vs. 10.7 months for EXTREME, translating into an HR of 0.77 (P = .0034). In this analysis as well as in the pembrolizumab monotherapy combination, there was no difference in PFS or response rates, but responses in the pembrolizumab arm were more durable.

In this comparison, treatment-related adverse events were generally similar between the groups, although there were 10 treatment-related deaths with pembrolizumab, compared with eight in the EXTREME arm.

There was one immune-related death, from pneumonitis, in the pembrolizumab arm, vs. none in the EXTREME arm. Hypothyroidism, pneumonitis, hyperthyroidism and colitis were more frequent with pembrolizumab, whereas infusion reactions and severe skin reactions were more frequent with EXTREME.

“There are further analyses of biomarker and clinical predictors that will be forthcoming from this study, and these may eventually optimally guide the choice of whether to administer pembrolizumab alone or in the novel combination, Dr. Burtness said at the briefing.

“What’s extremely important also is that for a subgroup of patients with high expression of PD-L1, we can probably remove the cisplatin and have a good outcome with immunotherapy alone,” Dr. Machiels said.

He said that more work needs to be done to determine which patients are most likely to benefit from immunotherapy in the recurrent/metastatic setting, and “we have to see how we can now bring this active drug to the curative treatment of the patient, in combination with chemoradiation.”

The study was funded by Merck Sharp & Dohme. Dr. Burtness disclosed being and advisory board member and receiving travel expenses from MSD and others. Dr. Machiels disclosed speaker honoraria, travel expenses, and an uncompensated advisory role with MSD.

SOURCE: Burtness B et al. ESMO 2018. Abstract LBA8_PR.

MUNICH – In patients with recurrent or metastatic head and neck squamous cell carcinoma expressing programmed death ligand-1 (PDL-1), the immune checkpoint inhibitor pembrolizumab alone or in combination with chemotherapy improved overall survival, compared with the EXTREME chemotherapy regimen, reported investigators in the Keynote 048 trial.

Neil Osterweil/MDedge News

Overall survival (OS) among patients with a PD-L1 combined positive score (CPS) of 20 or greater treated with pembrolizumab (Keytruda) monotherapy was 14.9 months compared with 10.7 months for patients treated with the EXTREME regimen, a combination of cetuximab (Erbitux), carboplatin or cisplatin, and 5-fluorouracil.

A similar overall survival benefit was seen in patients with a CPS of 1 or greater, and in the total population of patients treated with pembrolizumab plus chemotherapy followed by pembrolizumab maintenance compared with EXTREME chemotherapy, Barbara Burtness, MD, of Yale Cancer Center, New Haven, Conn.

There were no differences in response rates between either pembrolizumab monotherapy or in combination compared with chemotherapy alone, but responses were more durable with the checkpoint inhibitor than with chemotherapy.

“Pembrolizumab alone and pembrolizumab given with platinum and 5-fluorouracil should represent new standards of care for the first-line treatment of metastatic head and neck carcinoma. Immune checkpoint monotherapy with pembrolizumab allows patients to live longer and has a better safety profile than the previous standard for those patients whose tumors express PD-L1,” she said at a briefing prior to her presentation of the data in a presidential symposium at the European Society for Medical Oncology Congress.

“This is the first time since 10 years that we show an improvement in survival for this group of patients,” said Jean-Pascal Machiels, MD, of University Clinic Saint-Luc, Brussels, the invited discussant for the briefing and the symposium.

The CPS is a ratio of PD-L1-positive tumor cells, lymphocytes, and macrophages to the total numbers of cells counted multiplied by 100. The investigators looked at progression-free survival (PFS) and OS in three cohorts of patients with squamous cell carcinomas of the oropharynx, oral cavity, hypopharynx, or larynx that were recurrent or metastatic and were incurable by local therapies. They compared pembrolizumab monotherapy with the EXTREME regimen, and pembrolizumab plus chemotherapy (as described in the following paragraph) with EXTREME.

A total of 882 patients were enrolled and stratified by PD-L1 expression (on 50% or greater of tumor cells, or less than 50%), p16 positive or negative status in the oropharynx, and Eastern Cooperative Oncology Group performance status of 0 or 1. The patients were then randomly assigned on a 1:1:1 basis to either pembrolizumab monotherapy at 200 mg every 3 weeks for up to 35 cycles, pembrolizumab plus a standard chemotherapy regimen (carboplatin to an area-under-the curve [AUC] of 5 or cisplatin 100 mg/m² plus 5-FU 1000 mg/m2 ^per day for 4 days for six cycles, followed by pembrolizumab maintenance for up to 35 cycles or EXTREME (cetuximab at a loading dose of 400 mg/m² followed by 250 mg/m² once weekly plus the chemotherapy regimen described above, followed by maintenance cetuximab).
 

Pembrolizumab monotherapy vs. EXTREME

For the coprimary endpoint of OS in the CPS 20 or greater population, pembrolizumab was associated with significantly better survival than EXTREME at both the 12- and 24-month time points (56.9% vs. 44.9%, and 38.3% vs. 22,1%, respectively). After a minimum follow-up of 17 months, the median OS was 14.9 months with pembrolizumab, vs. 10.7 months for EXTREME. The hazard ratio (HR) for death with pembrolizumab was 0.61 (P = .0007).

The median OS in the CPS 1 or greater population was 12.3 months and 10.3 months, respectively (HR 0.78, P = .0086).

There were no differences between the arms in PFS, however, either in the CPS 20 or greater or CPS 1 or greater populations.

Although, as noted, response rates did not differ between the groups, the median duration of response was 20.9 months with pembrolizumab in both the CPS 20 and CPS 1 populations, compared with 4.2 and 4.5 months, respectively, for EXTREME.

Treatment-related adverse events of any grade occurred in 58% of patients in the monotherapy arm, vs. 96.9% in the EXTREME arm. Fatal adverse events occurred in 1% vs. 2.8%, and events leading to drug discontinuation occurred in 4.7% vs. 19.9%, respectively. There were more immune-mediated events in the pembrolizumab arm, including one death (from pneumonitis) vs. no deaths from immune-related causes in the EXTREME arm.
 

Pembrolizumab plus chemo vs. EXTREME

The combination of pembrolizumab was also superior to EXTREME in the total population, with 12- and 24-month OS rates of 53% vs. 43.9%, and 29% vs. 18.7%, respectively. The median OS was 13 months with the pembrolizumab/chemo combination, vs. 10.7 months for EXTREME, translating into an HR of 0.77 (P = .0034). In this analysis as well as in the pembrolizumab monotherapy combination, there was no difference in PFS or response rates, but responses in the pembrolizumab arm were more durable.

In this comparison, treatment-related adverse events were generally similar between the groups, although there were 10 treatment-related deaths with pembrolizumab, compared with eight in the EXTREME arm.

There was one immune-related death, from pneumonitis, in the pembrolizumab arm, vs. none in the EXTREME arm. Hypothyroidism, pneumonitis, hyperthyroidism and colitis were more frequent with pembrolizumab, whereas infusion reactions and severe skin reactions were more frequent with EXTREME.

“There are further analyses of biomarker and clinical predictors that will be forthcoming from this study, and these may eventually optimally guide the choice of whether to administer pembrolizumab alone or in the novel combination, Dr. Burtness said at the briefing.

“What’s extremely important also is that for a subgroup of patients with high expression of PD-L1, we can probably remove the cisplatin and have a good outcome with immunotherapy alone,” Dr. Machiels said.

He said that more work needs to be done to determine which patients are most likely to benefit from immunotherapy in the recurrent/metastatic setting, and “we have to see how we can now bring this active drug to the curative treatment of the patient, in combination with chemoradiation.”

The study was funded by Merck Sharp & Dohme. Dr. Burtness disclosed being and advisory board member and receiving travel expenses from MSD and others. Dr. Machiels disclosed speaker honoraria, travel expenses, and an uncompensated advisory role with MSD.

SOURCE: Burtness B et al. ESMO 2018. Abstract LBA8_PR.

Over one-third of psoriasis patients have PsA

About two-thirds of patients with psoriasis in a national registry also had psoriatic arthritis (PsA) and/or psoriasis in at least one challenging-to-treat (CTT) area, and one-quarter had both, according to Kristina Callis Duffin, MD, of the University of Utah, Salt Lake City, and her associates.

Their analysis included 2,042 psoriasis patients who were enrolled in the Corrona Psoriasis Registry between April 2015 and May 2018 and initiated biologic treatment during that time. The mean age was 49.6 years, 80% of the patients were white, and 51% were obese. Mean disease duration was 19.9 years and 89.2% of the patients had moderate to severe disease. CTT areas include the scalp, nails, and palmoplantar areas.

A total of 784 people in the cohort (38.4%) had PsA, 778 (38.1%) had scalp psoriasis, 326 (16.0%) had nail psoriasis, 223 (10.9%) had palmoplantar psoriasis, and 535 (26.2%) had both PsA and psoriasis in at least two CTT areas. The most common combinations were PsA plus scalp psoriasis and PsA plus nail and scalp psoriasis.

“These results indicate a need to further characterize patients with psoriasis who have PsA and CTT areas and evaluate the impact of these factors to better understand their treatment needs,” the investigators noted.

The Corrona registry has been supported by numerous pharmaceutical companies, and the study authors reported numerous financial relationships with industry; two authors are Novartis employees.

Secukinumab effective for slowing radiographic progression in active PsA

Treatment with secukinumab significantly reduced radiographic progression in patients with active PsA, according to Désirée van der Heijde, MD, PhD, professor of rheumatology at Leiden University Medical Center, and her associates.

The results come from an analysis of the FUTURE 5 trial, a study of 996 patients with active PsA despite previous NSAID treatment, disease-modifying antirheumatic drug treatment, or anti–tumor necrosis factor (TNF) therapy. Patients were randomized to receive 300 mg subcutaneous secukinumab with loading dose, 150 mg secukinumab with loading dose, 150 mg secukinumab without loading dose, or placebo, at baseline; weeks 1, 2, 3, and 4; then every 4 weeks.

After 24 weeks, the mean change in van der Heijde–modified Total Sharp Score for PsA was 0.08 for the 300-mg secukinumab group (P less than .01), 0.17 for the 150-mg secukinumab with loading dose group (P less than .05), a reduction of 0.09 for the 150-mg secukinumab without loading dose group (P less than .01), and 0.50 for the placebo group. Lower radiographic progression was seen regardless of prior anti-TNF or concomitant methotrexate treatment.

The study was funded by Novartis. The study authors reported financial disclosures with numerous companies; five authors are Novartis employees.

Tildrakizumab sustains efficacy in plaque psoriasis treatment after 1 year

Nearly all patients receiving the interleukin-23 inhibitor tildrakizumab for the treatment of moderate to severe plaque psoriasis maintained or improved their Psoriasis Area and Severity Index (PASI) response rate after 52 weeks of treatment, compared with their response after 28 weeks.

The analysis, conducted by Boni E. Elewski, MD, of the University of Alabama at Birmingham, and her associates, included 352 patients who received 100 mg tildrakizumab and 313 who received 200 mg tildrakizumab. Treatment was received at baseline, at 4 weeks, and then every 12 weeks afterward.

At week 28, the proportions of patients achieving PASI 100, PASI 90-99, PASI 75-89, and PASI 50-74 at week 28 were 25.9%, 38.4%, 25.3%, and 10.5%, respectively, among those treated with the 100-mg dose. The proportions were 24.6%, 24.3%, 19.5%, and 31.6%, respectively, among those treated with the 200-mg dose.

In patients who achieved at least PASI 90 on either dose at week 28, 88.9%-89.4% maintained that response at week 52. For patients with PASI 75-89, 39.3%-40.4% maintained that response and 33.7%-41.0% achieved a PASI 90 response. At week 52, in patients with PASI 50-74, 20.2%-29.7% achieved at least a PASI 90, 52.5%-64.9% achieved PASI 75, and only 2.6% of patients on either dose had fallen below PASI 50.

Four study authors reported being clinical investigators on studies sponsored by Merck and Sun Pharmaceuticals; five authors are employees of Sun Pharmaceuticals.
 

Halobetasol/tazarotene combination most effective for plaque psoriasis treatment

A fixed combination of halobetasol propionate 0.01% and tazarotene 0.045% lotion provided a synergistic effect over either component on its own for the treatment of plaque psoriasis, according to Leon H. Kircik, MD, of Indiana University, Indianapolis, and his associates.

The investigators performed a post hoc analysis of 212 patients with moderate to severe plaque psoriasis randomized to receive either the halobetasol/tazarotene combination, halobetasol only, tazarotene only, or vehicle only for 8 weeks, with follow-up at 12 weeks. Treatment success was based on the proportion of patients who achieved at least a 2-grade improvement in the Investigator Global Assessment (IGA) score, IGA scores of “clear” or “almost clear,” and percent change from baseline in IGA multiplied by Body Surface Area (BSA) composite score (IGAxBSA). “Synergy was calculated by summing up the contribution of the individual active ingredients (HP and TAZ) to overall efficacy and comparing to the efficacy achieved with HP/TAZ lotion relative to vehicle,” the authors explained.

Relative to vehicle, treatment success for halobetasol/tazarotene after 8 weeks was 42.8%, 23.6% for halobetasol alone, and 9.0% for tazarotene alone. After 12 weeks, the difference was 31.3%, 14.1%, and 5.9%, respectively. The percent change in IGAxBSA scores from baseline after 8 weeks, relative to vehicle, were 51.6%, 37.3%, and 3.3%, respectively. After 12 weeks, the change was 47.3%, 25.7%, and 8.6%, respectively.

After 8 weeks, the synergy ratio for treatment success and IGAxBSA scores for the halobetasol/tazarotene combination was 1.3. After 12 weeks, the synergy ratio for treatment success was 1.6 and the ratio for IGAxBSA scores was 1.4.

“By combining two agents into one once-daily formulation, this novel formulation reduces the number of product applications and may help patient adherence,” the study authors noted.

Dr. Kircik reported serving as a consultant and investigator for Valeant Pharmaceuticals. One study author is an employee of Bausch Health and Ortho Dermatologics, and another is an employee of Dow Pharmaceutical Sciences (a division of Valeant).

Brodalumab demonstrates low immunogenicity in moderate to severe psoriasis

The immunogenicity of brodalumab in patients with moderate to severe plaque psoriasis was low and did not compromise the efficacy or safety profile of the drug, according to Kristian Reich, MD, of Dermatologikum Berlin and SCIderm Research Institute in Hamburg, Germany, and his associates.

Data from a 12-week, phase 2 trial with a 352-week, open-label extension and three 52-week phase 3 trials were included in the analysis. Antidrug antibodies (ADAs) were tested, and positive samples were further analyzed for neutralizing ADAs by a cell-based assay.

Out of the 4,461 patients who received brodalumab, 122 (2.7%) were positive for ADAs after starting brodalumab. The incidence rate ranged from 1.9% to 3.4% between all dosing groups (140 mg, 210 mg, variable dosing, and 210 mg of brodalumab after ustekinumab). In 58 (1.4%) of patients, ADAs were transient. No patients had neutralizing ADAs, and no evidence of altered pharmacokinetics, loss of efficacy, or changes in the safety profile of brodalumab in subjects positive for ADAs was seen.

No significant difference was seen in the incidence rate of hypersensitivity or injection site reactions in brodalumab, compared with placebo or ustekinumab. The most common injection site reactions were injection site pain, erythema, and bruising.

The study was supported by Amgen. The study authors reported numerous disclosures. Two authors are employees of Leo Pharma, one author is a former employee of the company.
 

Secukinumab improves patient-reported outcomes in CTT psoriasis

Treatment with secukinumab significantly improved patient-reported outcomes such as fatigue, itch, pain, and quality of life measures in patients with CTT psoriasis after 6 months, according to Jerry Bagel, MD, of the Psoriasis Treatment Center of Central New Jersey, East Windsor, and his associates.

A total of 68 patients with psoriasis localized to at least one CTT area who were enrolled in the Corrona Psoriasis Registry from April 15, 2015, through May 10, 2018, and were receiving secukinumab for the entirety of the 6-month study period were included in the analysis. Patient-reported outcomes included in the analysis were fatigue, itch, pain, Dermatology Quality of Life Index (DLQI) score, and Work Productivity and Activity Impairment (WPAI) scale.

The mean age at enrollment was 51.2 years and almost 80% of patients were white. Mean psoriasis duration was 21.8 years and nearly half had PsA.

Visual analog scale scores improved over baseline for fatigue (mean, 23.2 vs. 33.2; P = .01), itch (20.9 vs. 49.6; P less than .0001), and pain (12.1 vs. 33.8; P less than .0001). DLQI scores also improved (2.9 vs. 8.1; P less than .0001), and the proportion of patients who reported that psoriasis had at least a moderate effect on their life was reduced after 6 months (22.1% vs. 59.7%; P less than .0001).

Based on WPAI results, patients experienced significant improvements in the percentage of daily activities impaired (mean, 9.5% vs 17.5%; P = .0075); of the 42 patients who were employed, both impairment percentage (3.7% vs. 11.2%; P = .0148) and percentage of work hours affected (4.9% vs. 11.9%; P = .0486) were reduced from baseline.

“These results are consistent with previous reports from secukinumab clinical trials; however, additional real-world studies are needed to evaluate the long-term effectiveness of secukinumab for improving [patient-reported outcomes] in patients with psoriasis in CTT areas,” the authors noted.

The Corrona registry has been supported by numerous pharmaceutical companies, and several study authors reported various disclosures with industry. Two authors are Novartis employees. The study was supported by Novartis; the company participated in the interpretation of data and review and approval of the abstract.


These posters were presented at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. SDEF and this news organization are owned by the same parent company.

[email protected]

Over one-third of psoriasis patients have PsA

About two-thirds of patients with psoriasis in a national registry also had psoriatic arthritis (PsA) and/or psoriasis in at least one challenging-to-treat (CTT) area, and one-quarter had both, according to Kristina Callis Duffin, MD, of the University of Utah, Salt Lake City, and her associates.

Their analysis included 2,042 psoriasis patients who were enrolled in the Corrona Psoriasis Registry between April 2015 and May 2018 and initiated biologic treatment during that time. The mean age was 49.6 years, 80% of the patients were white, and 51% were obese. Mean disease duration was 19.9 years and 89.2% of the patients had moderate to severe disease. CTT areas include the scalp, nails, and palmoplantar areas.

A total of 784 people in the cohort (38.4%) had PsA, 778 (38.1%) had scalp psoriasis, 326 (16.0%) had nail psoriasis, 223 (10.9%) had palmoplantar psoriasis, and 535 (26.2%) had both PsA and psoriasis in at least two CTT areas. The most common combinations were PsA plus scalp psoriasis and PsA plus nail and scalp psoriasis.

“These results indicate a need to further characterize patients with psoriasis who have PsA and CTT areas and evaluate the impact of these factors to better understand their treatment needs,” the investigators noted.

The Corrona registry has been supported by numerous pharmaceutical companies, and the study authors reported numerous financial relationships with industry; two authors are Novartis employees.

Secukinumab effective for slowing radiographic progression in active PsA

Treatment with secukinumab significantly reduced radiographic progression in patients with active PsA, according to Désirée van der Heijde, MD, PhD, professor of rheumatology at Leiden University Medical Center, and her associates.

The results come from an analysis of the FUTURE 5 trial, a study of 996 patients with active PsA despite previous NSAID treatment, disease-modifying antirheumatic drug treatment, or anti–tumor necrosis factor (TNF) therapy. Patients were randomized to receive 300 mg subcutaneous secukinumab with loading dose, 150 mg secukinumab with loading dose, 150 mg secukinumab without loading dose, or placebo, at baseline; weeks 1, 2, 3, and 4; then every 4 weeks.

After 24 weeks, the mean change in van der Heijde–modified Total Sharp Score for PsA was 0.08 for the 300-mg secukinumab group (P less than .01), 0.17 for the 150-mg secukinumab with loading dose group (P less than .05), a reduction of 0.09 for the 150-mg secukinumab without loading dose group (P less than .01), and 0.50 for the placebo group. Lower radiographic progression was seen regardless of prior anti-TNF or concomitant methotrexate treatment.

The study was funded by Novartis. The study authors reported financial disclosures with numerous companies; five authors are Novartis employees.

Tildrakizumab sustains efficacy in plaque psoriasis treatment after 1 year

Nearly all patients receiving the interleukin-23 inhibitor tildrakizumab for the treatment of moderate to severe plaque psoriasis maintained or improved their Psoriasis Area and Severity Index (PASI) response rate after 52 weeks of treatment, compared with their response after 28 weeks.

The analysis, conducted by Boni E. Elewski, MD, of the University of Alabama at Birmingham, and her associates, included 352 patients who received 100 mg tildrakizumab and 313 who received 200 mg tildrakizumab. Treatment was received at baseline, at 4 weeks, and then every 12 weeks afterward.

At week 28, the proportions of patients achieving PASI 100, PASI 90-99, PASI 75-89, and PASI 50-74 at week 28 were 25.9%, 38.4%, 25.3%, and 10.5%, respectively, among those treated with the 100-mg dose. The proportions were 24.6%, 24.3%, 19.5%, and 31.6%, respectively, among those treated with the 200-mg dose.

In patients who achieved at least PASI 90 on either dose at week 28, 88.9%-89.4% maintained that response at week 52. For patients with PASI 75-89, 39.3%-40.4% maintained that response and 33.7%-41.0% achieved a PASI 90 response. At week 52, in patients with PASI 50-74, 20.2%-29.7% achieved at least a PASI 90, 52.5%-64.9% achieved PASI 75, and only 2.6% of patients on either dose had fallen below PASI 50.

Four study authors reported being clinical investigators on studies sponsored by Merck and Sun Pharmaceuticals; five authors are employees of Sun Pharmaceuticals.
 

Halobetasol/tazarotene combination most effective for plaque psoriasis treatment

A fixed combination of halobetasol propionate 0.01% and tazarotene 0.045% lotion provided a synergistic effect over either component on its own for the treatment of plaque psoriasis, according to Leon H. Kircik, MD, of Indiana University, Indianapolis, and his associates.

The investigators performed a post hoc analysis of 212 patients with moderate to severe plaque psoriasis randomized to receive either the halobetasol/tazarotene combination, halobetasol only, tazarotene only, or vehicle only for 8 weeks, with follow-up at 12 weeks. Treatment success was based on the proportion of patients who achieved at least a 2-grade improvement in the Investigator Global Assessment (IGA) score, IGA scores of “clear” or “almost clear,” and percent change from baseline in IGA multiplied by Body Surface Area (BSA) composite score (IGAxBSA). “Synergy was calculated by summing up the contribution of the individual active ingredients (HP and TAZ) to overall efficacy and comparing to the efficacy achieved with HP/TAZ lotion relative to vehicle,” the authors explained.

Relative to vehicle, treatment success for halobetasol/tazarotene after 8 weeks was 42.8%, 23.6% for halobetasol alone, and 9.0% for tazarotene alone. After 12 weeks, the difference was 31.3%, 14.1%, and 5.9%, respectively. The percent change in IGAxBSA scores from baseline after 8 weeks, relative to vehicle, were 51.6%, 37.3%, and 3.3%, respectively. After 12 weeks, the change was 47.3%, 25.7%, and 8.6%, respectively.

After 8 weeks, the synergy ratio for treatment success and IGAxBSA scores for the halobetasol/tazarotene combination was 1.3. After 12 weeks, the synergy ratio for treatment success was 1.6 and the ratio for IGAxBSA scores was 1.4.

“By combining two agents into one once-daily formulation, this novel formulation reduces the number of product applications and may help patient adherence,” the study authors noted.

Dr. Kircik reported serving as a consultant and investigator for Valeant Pharmaceuticals. One study author is an employee of Bausch Health and Ortho Dermatologics, and another is an employee of Dow Pharmaceutical Sciences (a division of Valeant).

Brodalumab demonstrates low immunogenicity in moderate to severe psoriasis

The immunogenicity of brodalumab in patients with moderate to severe plaque psoriasis was low and did not compromise the efficacy or safety profile of the drug, according to Kristian Reich, MD, of Dermatologikum Berlin and SCIderm Research Institute in Hamburg, Germany, and his associates.

Data from a 12-week, phase 2 trial with a 352-week, open-label extension and three 52-week phase 3 trials were included in the analysis. Antidrug antibodies (ADAs) were tested, and positive samples were further analyzed for neutralizing ADAs by a cell-based assay.

Out of the 4,461 patients who received brodalumab, 122 (2.7%) were positive for ADAs after starting brodalumab. The incidence rate ranged from 1.9% to 3.4% between all dosing groups (140 mg, 210 mg, variable dosing, and 210 mg of brodalumab after ustekinumab). In 58 (1.4%) of patients, ADAs were transient. No patients had neutralizing ADAs, and no evidence of altered pharmacokinetics, loss of efficacy, or changes in the safety profile of brodalumab in subjects positive for ADAs was seen.

No significant difference was seen in the incidence rate of hypersensitivity or injection site reactions in brodalumab, compared with placebo or ustekinumab. The most common injection site reactions were injection site pain, erythema, and bruising.

The study was supported by Amgen. The study authors reported numerous disclosures. Two authors are employees of Leo Pharma, one author is a former employee of the company.
 

Secukinumab improves patient-reported outcomes in CTT psoriasis

Treatment with secukinumab significantly improved patient-reported outcomes such as fatigue, itch, pain, and quality of life measures in patients with CTT psoriasis after 6 months, according to Jerry Bagel, MD, of the Psoriasis Treatment Center of Central New Jersey, East Windsor, and his associates.

A total of 68 patients with psoriasis localized to at least one CTT area who were enrolled in the Corrona Psoriasis Registry from April 15, 2015, through May 10, 2018, and were receiving secukinumab for the entirety of the 6-month study period were included in the analysis. Patient-reported outcomes included in the analysis were fatigue, itch, pain, Dermatology Quality of Life Index (DLQI) score, and Work Productivity and Activity Impairment (WPAI) scale.

The mean age at enrollment was 51.2 years and almost 80% of patients were white. Mean psoriasis duration was 21.8 years and nearly half had PsA.

Visual analog scale scores improved over baseline for fatigue (mean, 23.2 vs. 33.2; P = .01), itch (20.9 vs. 49.6; P less than .0001), and pain (12.1 vs. 33.8; P less than .0001). DLQI scores also improved (2.9 vs. 8.1; P less than .0001), and the proportion of patients who reported that psoriasis had at least a moderate effect on their life was reduced after 6 months (22.1% vs. 59.7%; P less than .0001).

Based on WPAI results, patients experienced significant improvements in the percentage of daily activities impaired (mean, 9.5% vs 17.5%; P = .0075); of the 42 patients who were employed, both impairment percentage (3.7% vs. 11.2%; P = .0148) and percentage of work hours affected (4.9% vs. 11.9%; P = .0486) were reduced from baseline.

“These results are consistent with previous reports from secukinumab clinical trials; however, additional real-world studies are needed to evaluate the long-term effectiveness of secukinumab for improving [patient-reported outcomes] in patients with psoriasis in CTT areas,” the authors noted.

The Corrona registry has been supported by numerous pharmaceutical companies, and several study authors reported various disclosures with industry. Two authors are Novartis employees. The study was supported by Novartis; the company participated in the interpretation of data and review and approval of the abstract.


These posters were presented at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. SDEF and this news organization are owned by the same parent company.

[email protected]

Over one-third of psoriasis patients have PsA

About two-thirds of patients with psoriasis in a national registry also had psoriatic arthritis (PsA) and/or psoriasis in at least one challenging-to-treat (CTT) area, and one-quarter had both, according to Kristina Callis Duffin, MD, of the University of Utah, Salt Lake City, and her associates.

Their analysis included 2,042 psoriasis patients who were enrolled in the Corrona Psoriasis Registry between April 2015 and May 2018 and initiated biologic treatment during that time. The mean age was 49.6 years, 80% of the patients were white, and 51% were obese. Mean disease duration was 19.9 years and 89.2% of the patients had moderate to severe disease. CTT areas include the scalp, nails, and palmoplantar areas.

A total of 784 people in the cohort (38.4%) had PsA, 778 (38.1%) had scalp psoriasis, 326 (16.0%) had nail psoriasis, 223 (10.9%) had palmoplantar psoriasis, and 535 (26.2%) had both PsA and psoriasis in at least two CTT areas. The most common combinations were PsA plus scalp psoriasis and PsA plus nail and scalp psoriasis.

“These results indicate a need to further characterize patients with psoriasis who have PsA and CTT areas and evaluate the impact of these factors to better understand their treatment needs,” the investigators noted.

The Corrona registry has been supported by numerous pharmaceutical companies, and the study authors reported numerous financial relationships with industry; two authors are Novartis employees.

Secukinumab effective for slowing radiographic progression in active PsA

Treatment with secukinumab significantly reduced radiographic progression in patients with active PsA, according to Désirée van der Heijde, MD, PhD, professor of rheumatology at Leiden University Medical Center, and her associates.

The results come from an analysis of the FUTURE 5 trial, a study of 996 patients with active PsA despite previous NSAID treatment, disease-modifying antirheumatic drug treatment, or anti–tumor necrosis factor (TNF) therapy. Patients were randomized to receive 300 mg subcutaneous secukinumab with loading dose, 150 mg secukinumab with loading dose, 150 mg secukinumab without loading dose, or placebo, at baseline; weeks 1, 2, 3, and 4; then every 4 weeks.

After 24 weeks, the mean change in van der Heijde–modified Total Sharp Score for PsA was 0.08 for the 300-mg secukinumab group (P less than .01), 0.17 for the 150-mg secukinumab with loading dose group (P less than .05), a reduction of 0.09 for the 150-mg secukinumab without loading dose group (P less than .01), and 0.50 for the placebo group. Lower radiographic progression was seen regardless of prior anti-TNF or concomitant methotrexate treatment.

The study was funded by Novartis. The study authors reported financial disclosures with numerous companies; five authors are Novartis employees.

Tildrakizumab sustains efficacy in plaque psoriasis treatment after 1 year

Nearly all patients receiving the interleukin-23 inhibitor tildrakizumab for the treatment of moderate to severe plaque psoriasis maintained or improved their Psoriasis Area and Severity Index (PASI) response rate after 52 weeks of treatment, compared with their response after 28 weeks.

The analysis, conducted by Boni E. Elewski, MD, of the University of Alabama at Birmingham, and her associates, included 352 patients who received 100 mg tildrakizumab and 313 who received 200 mg tildrakizumab. Treatment was received at baseline, at 4 weeks, and then every 12 weeks afterward.

At week 28, the proportions of patients achieving PASI 100, PASI 90-99, PASI 75-89, and PASI 50-74 at week 28 were 25.9%, 38.4%, 25.3%, and 10.5%, respectively, among those treated with the 100-mg dose. The proportions were 24.6%, 24.3%, 19.5%, and 31.6%, respectively, among those treated with the 200-mg dose.

In patients who achieved at least PASI 90 on either dose at week 28, 88.9%-89.4% maintained that response at week 52. For patients with PASI 75-89, 39.3%-40.4% maintained that response and 33.7%-41.0% achieved a PASI 90 response. At week 52, in patients with PASI 50-74, 20.2%-29.7% achieved at least a PASI 90, 52.5%-64.9% achieved PASI 75, and only 2.6% of patients on either dose had fallen below PASI 50.

Four study authors reported being clinical investigators on studies sponsored by Merck and Sun Pharmaceuticals; five authors are employees of Sun Pharmaceuticals.
 

Halobetasol/tazarotene combination most effective for plaque psoriasis treatment

A fixed combination of halobetasol propionate 0.01% and tazarotene 0.045% lotion provided a synergistic effect over either component on its own for the treatment of plaque psoriasis, according to Leon H. Kircik, MD, of Indiana University, Indianapolis, and his associates.

The investigators performed a post hoc analysis of 212 patients with moderate to severe plaque psoriasis randomized to receive either the halobetasol/tazarotene combination, halobetasol only, tazarotene only, or vehicle only for 8 weeks, with follow-up at 12 weeks. Treatment success was based on the proportion of patients who achieved at least a 2-grade improvement in the Investigator Global Assessment (IGA) score, IGA scores of “clear” or “almost clear,” and percent change from baseline in IGA multiplied by Body Surface Area (BSA) composite score (IGAxBSA). “Synergy was calculated by summing up the contribution of the individual active ingredients (HP and TAZ) to overall efficacy and comparing to the efficacy achieved with HP/TAZ lotion relative to vehicle,” the authors explained.

Relative to vehicle, treatment success for halobetasol/tazarotene after 8 weeks was 42.8%, 23.6% for halobetasol alone, and 9.0% for tazarotene alone. After 12 weeks, the difference was 31.3%, 14.1%, and 5.9%, respectively. The percent change in IGAxBSA scores from baseline after 8 weeks, relative to vehicle, were 51.6%, 37.3%, and 3.3%, respectively. After 12 weeks, the change was 47.3%, 25.7%, and 8.6%, respectively.

After 8 weeks, the synergy ratio for treatment success and IGAxBSA scores for the halobetasol/tazarotene combination was 1.3. After 12 weeks, the synergy ratio for treatment success was 1.6 and the ratio for IGAxBSA scores was 1.4.

“By combining two agents into one once-daily formulation, this novel formulation reduces the number of product applications and may help patient adherence,” the study authors noted.

Dr. Kircik reported serving as a consultant and investigator for Valeant Pharmaceuticals. One study author is an employee of Bausch Health and Ortho Dermatologics, and another is an employee of Dow Pharmaceutical Sciences (a division of Valeant).

Brodalumab demonstrates low immunogenicity in moderate to severe psoriasis

The immunogenicity of brodalumab in patients with moderate to severe plaque psoriasis was low and did not compromise the efficacy or safety profile of the drug, according to Kristian Reich, MD, of Dermatologikum Berlin and SCIderm Research Institute in Hamburg, Germany, and his associates.

Data from a 12-week, phase 2 trial with a 352-week, open-label extension and three 52-week phase 3 trials were included in the analysis. Antidrug antibodies (ADAs) were tested, and positive samples were further analyzed for neutralizing ADAs by a cell-based assay.

Out of the 4,461 patients who received brodalumab, 122 (2.7%) were positive for ADAs after starting brodalumab. The incidence rate ranged from 1.9% to 3.4% between all dosing groups (140 mg, 210 mg, variable dosing, and 210 mg of brodalumab after ustekinumab). In 58 (1.4%) of patients, ADAs were transient. No patients had neutralizing ADAs, and no evidence of altered pharmacokinetics, loss of efficacy, or changes in the safety profile of brodalumab in subjects positive for ADAs was seen.

No significant difference was seen in the incidence rate of hypersensitivity or injection site reactions in brodalumab, compared with placebo or ustekinumab. The most common injection site reactions were injection site pain, erythema, and bruising.

The study was supported by Amgen. The study authors reported numerous disclosures. Two authors are employees of Leo Pharma, one author is a former employee of the company.
 

Secukinumab improves patient-reported outcomes in CTT psoriasis

Treatment with secukinumab significantly improved patient-reported outcomes such as fatigue, itch, pain, and quality of life measures in patients with CTT psoriasis after 6 months, according to Jerry Bagel, MD, of the Psoriasis Treatment Center of Central New Jersey, East Windsor, and his associates.

A total of 68 patients with psoriasis localized to at least one CTT area who were enrolled in the Corrona Psoriasis Registry from April 15, 2015, through May 10, 2018, and were receiving secukinumab for the entirety of the 6-month study period were included in the analysis. Patient-reported outcomes included in the analysis were fatigue, itch, pain, Dermatology Quality of Life Index (DLQI) score, and Work Productivity and Activity Impairment (WPAI) scale.

The mean age at enrollment was 51.2 years and almost 80% of patients were white. Mean psoriasis duration was 21.8 years and nearly half had PsA.

Visual analog scale scores improved over baseline for fatigue (mean, 23.2 vs. 33.2; P = .01), itch (20.9 vs. 49.6; P less than .0001), and pain (12.1 vs. 33.8; P less than .0001). DLQI scores also improved (2.9 vs. 8.1; P less than .0001), and the proportion of patients who reported that psoriasis had at least a moderate effect on their life was reduced after 6 months (22.1% vs. 59.7%; P less than .0001).

Based on WPAI results, patients experienced significant improvements in the percentage of daily activities impaired (mean, 9.5% vs 17.5%; P = .0075); of the 42 patients who were employed, both impairment percentage (3.7% vs. 11.2%; P = .0148) and percentage of work hours affected (4.9% vs. 11.9%; P = .0486) were reduced from baseline.

“These results are consistent with previous reports from secukinumab clinical trials; however, additional real-world studies are needed to evaluate the long-term effectiveness of secukinumab for improving [patient-reported outcomes] in patients with psoriasis in CTT areas,” the authors noted.

The Corrona registry has been supported by numerous pharmaceutical companies, and several study authors reported various disclosures with industry. Two authors are Novartis employees. The study was supported by Novartis; the company participated in the interpretation of data and review and approval of the abstract.


These posters were presented at Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar. SDEF and this news organization are owned by the same parent company.

[email protected]

CHICAGO—Among pediatric patients who receive IV dihydroergotamine (DHE) for headache, chest pain is a common side effect and reason for early cessation of DHE, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. Chest pain may not represent a serious cardiovascular problem, and patients who continue DHE despite chest pain have better chances of acute headache resolution, compared with patients who stop DHE, said Sara Fridinger, MD, a fellow with the Division of Neurology at Children’s Hospital of Philadelphia.

IV DHE is an effective headache treatment for children, but it has many side effects, including chest pain. Chest pain in pediatric patients who receive IV DHE may result from esophageal spasms, but it raises concerns about myocardial ischemia because of the drug’s vasospastic qualities, the researchers said.

To determine the incidence and significance of chest pain among pediatric patients who received IV DHE for headache, Dr. Fridinger and Christina Szperka, MD, Director of the Pediatric Headache Program at Children’s Hospital of Philadelphia, conducted a retrospective chart review. They examined data from pediatric patients at their hospital who received IV DHE between January 2014 and July 2016. They excluded patients who received DHE for secondary headache. Data from 183 patients (median age, 15.7; 81% female) were included in their analysis, including reports of chest pain and other side effects, EKG data, and cardiac enzymes.

Chest pain occurred in 27% (n = 49) of patients who received DHE. Chest pain occurred after the first dose in 33% of patients and after the second dose in 61%. All patients received premedication before the dose that caused chest pain, and metoclopramide was used as premedication in 80% of cases. No patients with chest pain had elevated troponin. Of the 31% of patients with chest pain who had EKG abnormalities, the abnormalities were either unchanged from baseline or deemed not clinically significant. Of patients with chest pain, 39% stopped DHE due to chest pain, whereas 61% continued with the DHE protocol.

Thirty-seven percent of patients who stopped DHE due to chest pain and 50% of those who continued DHE despite chest pain achieved resolution of the acute headache.

“It is reassuring that no patients were found to have elevated cardiac enzymes and no patients had frankly abnormal EKGs,” said Drs. Fridinger and Szperka.

CHICAGO—Among pediatric patients who receive IV dihydroergotamine (DHE) for headache, chest pain is a common side effect and reason for early cessation of DHE, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. Chest pain may not represent a serious cardiovascular problem, and patients who continue DHE despite chest pain have better chances of acute headache resolution, compared with patients who stop DHE, said Sara Fridinger, MD, a fellow with the Division of Neurology at Children’s Hospital of Philadelphia.

IV DHE is an effective headache treatment for children, but it has many side effects, including chest pain. Chest pain in pediatric patients who receive IV DHE may result from esophageal spasms, but it raises concerns about myocardial ischemia because of the drug’s vasospastic qualities, the researchers said.

To determine the incidence and significance of chest pain among pediatric patients who received IV DHE for headache, Dr. Fridinger and Christina Szperka, MD, Director of the Pediatric Headache Program at Children’s Hospital of Philadelphia, conducted a retrospective chart review. They examined data from pediatric patients at their hospital who received IV DHE between January 2014 and July 2016. They excluded patients who received DHE for secondary headache. Data from 183 patients (median age, 15.7; 81% female) were included in their analysis, including reports of chest pain and other side effects, EKG data, and cardiac enzymes.

Chest pain occurred in 27% (n = 49) of patients who received DHE. Chest pain occurred after the first dose in 33% of patients and after the second dose in 61%. All patients received premedication before the dose that caused chest pain, and metoclopramide was used as premedication in 80% of cases. No patients with chest pain had elevated troponin. Of the 31% of patients with chest pain who had EKG abnormalities, the abnormalities were either unchanged from baseline or deemed not clinically significant. Of patients with chest pain, 39% stopped DHE due to chest pain, whereas 61% continued with the DHE protocol.

Thirty-seven percent of patients who stopped DHE due to chest pain and 50% of those who continued DHE despite chest pain achieved resolution of the acute headache.

“It is reassuring that no patients were found to have elevated cardiac enzymes and no patients had frankly abnormal EKGs,” said Drs. Fridinger and Szperka.

CHICAGO—Among pediatric patients who receive IV dihydroergotamine (DHE) for headache, chest pain is a common side effect and reason for early cessation of DHE, according to a study presented at the 47th Annual Meeting of the Child Neurology Society. Chest pain may not represent a serious cardiovascular problem, and patients who continue DHE despite chest pain have better chances of acute headache resolution, compared with patients who stop DHE, said Sara Fridinger, MD, a fellow with the Division of Neurology at Children’s Hospital of Philadelphia.

IV DHE is an effective headache treatment for children, but it has many side effects, including chest pain. Chest pain in pediatric patients who receive IV DHE may result from esophageal spasms, but it raises concerns about myocardial ischemia because of the drug’s vasospastic qualities, the researchers said.

To determine the incidence and significance of chest pain among pediatric patients who received IV DHE for headache, Dr. Fridinger and Christina Szperka, MD, Director of the Pediatric Headache Program at Children’s Hospital of Philadelphia, conducted a retrospective chart review. They examined data from pediatric patients at their hospital who received IV DHE between January 2014 and July 2016. They excluded patients who received DHE for secondary headache. Data from 183 patients (median age, 15.7; 81% female) were included in their analysis, including reports of chest pain and other side effects, EKG data, and cardiac enzymes.

Chest pain occurred in 27% (n = 49) of patients who received DHE. Chest pain occurred after the first dose in 33% of patients and after the second dose in 61%. All patients received premedication before the dose that caused chest pain, and metoclopramide was used as premedication in 80% of cases. No patients with chest pain had elevated troponin. Of the 31% of patients with chest pain who had EKG abnormalities, the abnormalities were either unchanged from baseline or deemed not clinically significant. Of patients with chest pain, 39% stopped DHE due to chest pain, whereas 61% continued with the DHE protocol.

Thirty-seven percent of patients who stopped DHE due to chest pain and 50% of those who continued DHE despite chest pain achieved resolution of the acute headache.

“It is reassuring that no patients were found to have elevated cardiac enzymes and no patients had frankly abnormal EKGs,” said Drs. Fridinger and Szperka.

The US military enforces grooming standards to ensure the professional appearance and serviceability of soldiers in all operational settings. Although most individuals are able to uphold these regulations without incident, there is a growing cohort of servicemembers with skin diseases that were exacerbated or even initiated by haircuts, hairstyling, and shaving required to conform to these grooming standards. These skin diseases, which can affect both sexes and may not be appreciated until years into a soldier's service commitment, can have consequences related to individual morbidity and medical readiness for deployment, making it an important issue for medical practitioners to recognize and manage in servicemembers.

This review highlights several disorders of the pilosebaceous unit of the head and neck that can be caused or exacerbated by military grooming standards, including inflammatory hair disorders, traction alopecia, and pseudofolliculitis barbae. Discussion of each entity will include a review of susceptibility and causality as well as initial treatment options to consider (Table).

Inflammatory Hair Disorders

The proper appearance of servicemembers in uniform represents self-discipline and conformity to the high standards of the military. This transition occurs as a rite of passage for many new male recruits who receive shaved haircuts during their first days of basic training. Thereafter, male servicemembers are required to maintain a tapered appearance of the hair per military regulations.¹ Clipping hair closely to the scalp or shaving the head entirely are authorized and often encouraged; therefore, high and tight haircuts and buzz cuts are popular among male soldiers due to the general ease of care and ability to maintain the haircut themselves. Conversely, these styles require servicemembers to get weekly or biweekly haircuts that in turn can lead to chronic trauma and irritation. In more susceptible populations, inflammatory hair disorders such as acne keloidalis nuchae (AKN), dissecting cellulitis of the scalp, and folliculitis decalvans may be incited.

Acne Keloidalis Nuchae
Acne keloidalis nuchae, also called folliculitis keloidalis, is a chronic scarring folliculitis presenting with papules and plaques on the occiput and nape of the neck that may merge to form hypertrophic scars or keloids. This disorder most commonly develops in young black men but also can be seen in black females and white patients of both sexes.² Acne keloidalis nuchae shares many histologic features with central centrifugal cicatricial alopecia, which may suggest a similar pathogenesis. Apart from frequent haircuts, tight-collared shirts, such as those on military service uniforms, also have been associated with AKN. Because of these suspected etiologies, first-line treatment focuses on preventing further trauma by avoiding mechanical irritation and short haircuts, which may be difficult in the military setting. For earlier disease stages, topical and intralesional corticosteroids, oral retinoids, and topical and oral antibiotics are used for their anti-inflammatory properties.³ In refractory cases, surgical excision with healing by secondary intention may be attempted.⁴ Additional treatment options include the 1064-nm Nd:YAG and 810-nm diode lasers,³ UVB light therapy, CO₂ laser, and radiotherapy.

Dissecting Cellulitis of the Scalp
Similar to AKN, dissecting cellulitis of the scalp is another inflammatory hair disorder that is worsened by frequent short haircuts.⁵ Dissecting cellulitis of the scalp is a primary cicatricial alopecia proposed to be secondary to follicular occlusion. It often is seen in black males aged 20 to 40 years and is characterized by boggy suppurative nodules and cysts with draining sinus tracts, abscesses, and resultant scarring alopecia. Dissecting cellulitis of the scalp is part of the follicular occlusion tetrad, which also includes hidradenitis suppurativa, acne conglobata, and pilonidal cysts. First-line therapies include topical and oral antibiotics, topical retinoids, intralesional corticosteroids, incision and drainage of fluctuant nodules, and oral isotretinoin with or without rifampin. Alternative treatments include oral zinc supplementation, oral corticosteroids, tumor necrosis factor α inhibitors, laser therapies, radiotherapy, and surgical management with wide local excision or total scalpectomy.^6,7

Folliculitis Decalvans
Folliculitis decalvans is a primary cicatricial alopecia of the scalp that most commonly presents in middle-aged men without racial predilection.⁸ Folliculitis decalvans presents with multiple pustules, crusts, tufted hairs, and perifollicular hyperkeratosis, leading to scarring of the scalp, which often is most severe on the posterior vertex. Staphylococcus aureus is a presumed player in the pathogenesis of folliculitis decalvans with superantigens causing release of cytokines stimulating follicular destruction. Close haircuts in conformation with military grooming standards can contribute to this condition due to mechanical trauma and subsequent inflammation. It typically is diagnosed clinically, but if histologic confirmation is desired, a sample from the periphery of early lesions is preferred.⁹ Initial treatment consists of antibacterial shampoos, topical corticosteroids, topical antibiotics, and combination oral antibiotic therapy with rifampin and clindamycin. Studies using oral isotretinoin have shown variable results,^10,11 and the most effective treatment of recalcitrant lesions appears to be intralesional corticosteroids.¹²

Follicular and Scarring Disorders

In addition to inflammatory hair disorders, military grooming standards have been linked to the pathogenesis of diseases such as pseudofolliculitis barbae, traction alopecia, and keloids, specifically through irritation of the face, neck, and scalp, as well as damage to the follicular unit.⁵ These conditions develop because grooming regulations necessitate certain hair practices such as close shaving of facial and neck hair and keeping long hair secured relatively tightly to the scalp.

Pseudofolliculitis Barbae
Males in the military are obligated to keep their faces clean-shaven.¹ They may acquire a medical waiver for a specified beard length if deemed appropriate by the treating physician,¹ which often leads to the need for continual waiver renewal and also may warrant possible negative perception from peers, subordinates, and leadership. One of the most prevalent conditions that is closely associated with shaving is pseudofolliculitis barbae. The combination of close shaving and tightly coiled hairs causes the hairs to grow toward and penetrate the skin, particularly on the neck.¹³ In some cases, the hairs never actually exit the skin and simply curl within the superficial epidermis. A foreign body reaction often arises, leading to inflamed follicular papules and pustules. Affected individuals may experience pain, pruritus, and secondary infections. Postinflammatory hyperpigmentation, hypertrophic scarring, and keloid formation are common sequelae in cases of untreated disease. Pseudofolliculitis barbae also is exacerbated by pulling the skin taut and shaving against the grain, making behavioral interventions a key component in management of this condition. Preliminary recommendations include using a new or electric razor, leaving hair at least 2 mm in length, and shaving in the direction of hair growth. Other treatment options with varying effectiveness include daily alternation of a mild topical corticosteroid and one of the following: a topical retinoid, topical antibiotics, or glycolic acid. The only treatments that approach definitive cure are laser hair removal and electrolysis for which patient skin type plays an important role in laser selection.⁵

Traction Alopecia
Similar to their male counterparts, female military members must also present a conservative professional appearance, including hair that is neatly groomed.¹ If the length of the hair extends beyond the uniform collar, it must be inconspicuously fastened or pinned above the collar. As a result, loosely tied hair is unauthorized, and females with long hair must secure their hair tightly on a daily basis. Traction alopecia results from tight hairstyling over a prolonged period and commonly affects female soldiers. The etiology is presumed to be mechanical loosening of hair within the follicles, leading to inflammation. Although traditionally seen in black women along the frontal and temporal hairlines, traction alopecia has been identified in individuals of all races and can occur anywhere on the scalp.⁵ Perifollicular erythema may be the first sign, and papules and pustules may be visible. Although the hair loss in traction alopecia usually is reversible if the traction is ceased, end-stage disease may be permanent.6 Halting traction-inducing practices is paramount, and other treatment options that may slow progression include topical or oral antibiotics and topical or intralesional corticosteroids. Recovery of hair loss also may be aided by topical minoxidil.⁵

Keloids
Keloid formation is an important pathology to address, as it may result from several of the aforementioned conditions. Keloids are most commonly seen in black individuals but also can occur in Hispanic and Asian patients. The cause has not been fully elucidated but is thought to be a combination of dysfunctional fibroblasts with a genetic component based on racial predilection and twin concordance studies.⁵ The chest, shoulders, upper back, neck, and earlobes are particularly susceptible to keloid formation, which can appear from 1 to 24 years following dermal trauma.5 Unlike hypertrophic scars, keloids generally do not regress and frequently cause discomfort, pruritus, and emotional distress. They also can hinder wearing a military uniform. Sustained remission is problematic, making prevention a first-line approach, including proper care of wounds when they occur and avoiding elective procedures such as piercings and tattoos. Intralesional corticosteroids, adjuvant injections (eg, 5-fluorouracil), silicone sheeting, cryotherapy, radiation, laser therapy, and excision are some of the treatment options when keloids have formed.⁵

Final Comment

It is important to recognize military grooming standards as a cause or contributor to several diseases of the head and neck in military servicemembers. Specifically, frequent haircuts in male soldiers are associated with several inflammatory hair disorders, including AKN, dissecting cellulitis of the scalp, and folliculitis decalvans, while daily shaving predisposes individuals to pseudofolliculitis barbae with possible keloid formation. Females may develop traction alopecia from chronically tight, pulled back hairstyles. All of these conditions have health implications for the affected individuals and can compromise the military mission. Awareness, prevention, and recognition are key along with the knowledge base to provide anticipatory avoidance and initiate appropriate treatments, thereby mitigating these potential consequences.

The US military enforces grooming standards to ensure the professional appearance and serviceability of soldiers in all operational settings. Although most individuals are able to uphold these regulations without incident, there is a growing cohort of servicemembers with skin diseases that were exacerbated or even initiated by haircuts, hairstyling, and shaving required to conform to these grooming standards. These skin diseases, which can affect both sexes and may not be appreciated until years into a soldier's service commitment, can have consequences related to individual morbidity and medical readiness for deployment, making it an important issue for medical practitioners to recognize and manage in servicemembers.

This review highlights several disorders of the pilosebaceous unit of the head and neck that can be caused or exacerbated by military grooming standards, including inflammatory hair disorders, traction alopecia, and pseudofolliculitis barbae. Discussion of each entity will include a review of susceptibility and causality as well as initial treatment options to consider (Table).

Inflammatory Hair Disorders

The proper appearance of servicemembers in uniform represents self-discipline and conformity to the high standards of the military. This transition occurs as a rite of passage for many new male recruits who receive shaved haircuts during their first days of basic training. Thereafter, male servicemembers are required to maintain a tapered appearance of the hair per military regulations.¹ Clipping hair closely to the scalp or shaving the head entirely are authorized and often encouraged; therefore, high and tight haircuts and buzz cuts are popular among male soldiers due to the general ease of care and ability to maintain the haircut themselves. Conversely, these styles require servicemembers to get weekly or biweekly haircuts that in turn can lead to chronic trauma and irritation. In more susceptible populations, inflammatory hair disorders such as acne keloidalis nuchae (AKN), dissecting cellulitis of the scalp, and folliculitis decalvans may be incited.

Acne Keloidalis Nuchae
Acne keloidalis nuchae, also called folliculitis keloidalis, is a chronic scarring folliculitis presenting with papules and plaques on the occiput and nape of the neck that may merge to form hypertrophic scars or keloids. This disorder most commonly develops in young black men but also can be seen in black females and white patients of both sexes.² Acne keloidalis nuchae shares many histologic features with central centrifugal cicatricial alopecia, which may suggest a similar pathogenesis. Apart from frequent haircuts, tight-collared shirts, such as those on military service uniforms, also have been associated with AKN. Because of these suspected etiologies, first-line treatment focuses on preventing further trauma by avoiding mechanical irritation and short haircuts, which may be difficult in the military setting. For earlier disease stages, topical and intralesional corticosteroids, oral retinoids, and topical and oral antibiotics are used for their anti-inflammatory properties.³ In refractory cases, surgical excision with healing by secondary intention may be attempted.⁴ Additional treatment options include the 1064-nm Nd:YAG and 810-nm diode lasers,³ UVB light therapy, CO₂ laser, and radiotherapy.

Dissecting Cellulitis of the Scalp
Similar to AKN, dissecting cellulitis of the scalp is another inflammatory hair disorder that is worsened by frequent short haircuts.⁵ Dissecting cellulitis of the scalp is a primary cicatricial alopecia proposed to be secondary to follicular occlusion. It often is seen in black males aged 20 to 40 years and is characterized by boggy suppurative nodules and cysts with draining sinus tracts, abscesses, and resultant scarring alopecia. Dissecting cellulitis of the scalp is part of the follicular occlusion tetrad, which also includes hidradenitis suppurativa, acne conglobata, and pilonidal cysts. First-line therapies include topical and oral antibiotics, topical retinoids, intralesional corticosteroids, incision and drainage of fluctuant nodules, and oral isotretinoin with or without rifampin. Alternative treatments include oral zinc supplementation, oral corticosteroids, tumor necrosis factor α inhibitors, laser therapies, radiotherapy, and surgical management with wide local excision or total scalpectomy.^6,7

Folliculitis Decalvans
Folliculitis decalvans is a primary cicatricial alopecia of the scalp that most commonly presents in middle-aged men without racial predilection.⁸ Folliculitis decalvans presents with multiple pustules, crusts, tufted hairs, and perifollicular hyperkeratosis, leading to scarring of the scalp, which often is most severe on the posterior vertex. Staphylococcus aureus is a presumed player in the pathogenesis of folliculitis decalvans with superantigens causing release of cytokines stimulating follicular destruction. Close haircuts in conformation with military grooming standards can contribute to this condition due to mechanical trauma and subsequent inflammation. It typically is diagnosed clinically, but if histologic confirmation is desired, a sample from the periphery of early lesions is preferred.⁹ Initial treatment consists of antibacterial shampoos, topical corticosteroids, topical antibiotics, and combination oral antibiotic therapy with rifampin and clindamycin. Studies using oral isotretinoin have shown variable results,^10,11 and the most effective treatment of recalcitrant lesions appears to be intralesional corticosteroids.¹²

Follicular and Scarring Disorders

In addition to inflammatory hair disorders, military grooming standards have been linked to the pathogenesis of diseases such as pseudofolliculitis barbae, traction alopecia, and keloids, specifically through irritation of the face, neck, and scalp, as well as damage to the follicular unit.⁵ These conditions develop because grooming regulations necessitate certain hair practices such as close shaving of facial and neck hair and keeping long hair secured relatively tightly to the scalp.

Pseudofolliculitis Barbae
Males in the military are obligated to keep their faces clean-shaven.¹ They may acquire a medical waiver for a specified beard length if deemed appropriate by the treating physician,¹ which often leads to the need for continual waiver renewal and also may warrant possible negative perception from peers, subordinates, and leadership. One of the most prevalent conditions that is closely associated with shaving is pseudofolliculitis barbae. The combination of close shaving and tightly coiled hairs causes the hairs to grow toward and penetrate the skin, particularly on the neck.¹³ In some cases, the hairs never actually exit the skin and simply curl within the superficial epidermis. A foreign body reaction often arises, leading to inflamed follicular papules and pustules. Affected individuals may experience pain, pruritus, and secondary infections. Postinflammatory hyperpigmentation, hypertrophic scarring, and keloid formation are common sequelae in cases of untreated disease. Pseudofolliculitis barbae also is exacerbated by pulling the skin taut and shaving against the grain, making behavioral interventions a key component in management of this condition. Preliminary recommendations include using a new or electric razor, leaving hair at least 2 mm in length, and shaving in the direction of hair growth. Other treatment options with varying effectiveness include daily alternation of a mild topical corticosteroid and one of the following: a topical retinoid, topical antibiotics, or glycolic acid. The only treatments that approach definitive cure are laser hair removal and electrolysis for which patient skin type plays an important role in laser selection.⁵

Traction Alopecia
Similar to their male counterparts, female military members must also present a conservative professional appearance, including hair that is neatly groomed.¹ If the length of the hair extends beyond the uniform collar, it must be inconspicuously fastened or pinned above the collar. As a result, loosely tied hair is unauthorized, and females with long hair must secure their hair tightly on a daily basis. Traction alopecia results from tight hairstyling over a prolonged period and commonly affects female soldiers. The etiology is presumed to be mechanical loosening of hair within the follicles, leading to inflammation. Although traditionally seen in black women along the frontal and temporal hairlines, traction alopecia has been identified in individuals of all races and can occur anywhere on the scalp.⁵ Perifollicular erythema may be the first sign, and papules and pustules may be visible. Although the hair loss in traction alopecia usually is reversible if the traction is ceased, end-stage disease may be permanent.6 Halting traction-inducing practices is paramount, and other treatment options that may slow progression include topical or oral antibiotics and topical or intralesional corticosteroids. Recovery of hair loss also may be aided by topical minoxidil.⁵

Keloids
Keloid formation is an important pathology to address, as it may result from several of the aforementioned conditions. Keloids are most commonly seen in black individuals but also can occur in Hispanic and Asian patients. The cause has not been fully elucidated but is thought to be a combination of dysfunctional fibroblasts with a genetic component based on racial predilection and twin concordance studies.⁵ The chest, shoulders, upper back, neck, and earlobes are particularly susceptible to keloid formation, which can appear from 1 to 24 years following dermal trauma.5 Unlike hypertrophic scars, keloids generally do not regress and frequently cause discomfort, pruritus, and emotional distress. They also can hinder wearing a military uniform. Sustained remission is problematic, making prevention a first-line approach, including proper care of wounds when they occur and avoiding elective procedures such as piercings and tattoos. Intralesional corticosteroids, adjuvant injections (eg, 5-fluorouracil), silicone sheeting, cryotherapy, radiation, laser therapy, and excision are some of the treatment options when keloids have formed.⁵

Final Comment

It is important to recognize military grooming standards as a cause or contributor to several diseases of the head and neck in military servicemembers. Specifically, frequent haircuts in male soldiers are associated with several inflammatory hair disorders, including AKN, dissecting cellulitis of the scalp, and folliculitis decalvans, while daily shaving predisposes individuals to pseudofolliculitis barbae with possible keloid formation. Females may develop traction alopecia from chronically tight, pulled back hairstyles. All of these conditions have health implications for the affected individuals and can compromise the military mission. Awareness, prevention, and recognition are key along with the knowledge base to provide anticipatory avoidance and initiate appropriate treatments, thereby mitigating these potential consequences.

The US military enforces grooming standards to ensure the professional appearance and serviceability of soldiers in all operational settings. Although most individuals are able to uphold these regulations without incident, there is a growing cohort of servicemembers with skin diseases that were exacerbated or even initiated by haircuts, hairstyling, and shaving required to conform to these grooming standards. These skin diseases, which can affect both sexes and may not be appreciated until years into a soldier's service commitment, can have consequences related to individual morbidity and medical readiness for deployment, making it an important issue for medical practitioners to recognize and manage in servicemembers.

This review highlights several disorders of the pilosebaceous unit of the head and neck that can be caused or exacerbated by military grooming standards, including inflammatory hair disorders, traction alopecia, and pseudofolliculitis barbae. Discussion of each entity will include a review of susceptibility and causality as well as initial treatment options to consider (Table).

Inflammatory Hair Disorders

The proper appearance of servicemembers in uniform represents self-discipline and conformity to the high standards of the military. This transition occurs as a rite of passage for many new male recruits who receive shaved haircuts during their first days of basic training. Thereafter, male servicemembers are required to maintain a tapered appearance of the hair per military regulations.¹ Clipping hair closely to the scalp or shaving the head entirely are authorized and often encouraged; therefore, high and tight haircuts and buzz cuts are popular among male soldiers due to the general ease of care and ability to maintain the haircut themselves. Conversely, these styles require servicemembers to get weekly or biweekly haircuts that in turn can lead to chronic trauma and irritation. In more susceptible populations, inflammatory hair disorders such as acne keloidalis nuchae (AKN), dissecting cellulitis of the scalp, and folliculitis decalvans may be incited.

Acne Keloidalis Nuchae
Acne keloidalis nuchae, also called folliculitis keloidalis, is a chronic scarring folliculitis presenting with papules and plaques on the occiput and nape of the neck that may merge to form hypertrophic scars or keloids. This disorder most commonly develops in young black men but also can be seen in black females and white patients of both sexes.² Acne keloidalis nuchae shares many histologic features with central centrifugal cicatricial alopecia, which may suggest a similar pathogenesis. Apart from frequent haircuts, tight-collared shirts, such as those on military service uniforms, also have been associated with AKN. Because of these suspected etiologies, first-line treatment focuses on preventing further trauma by avoiding mechanical irritation and short haircuts, which may be difficult in the military setting. For earlier disease stages, topical and intralesional corticosteroids, oral retinoids, and topical and oral antibiotics are used for their anti-inflammatory properties.³ In refractory cases, surgical excision with healing by secondary intention may be attempted.⁴ Additional treatment options include the 1064-nm Nd:YAG and 810-nm diode lasers,³ UVB light therapy, CO₂ laser, and radiotherapy.

Dissecting Cellulitis of the Scalp
Similar to AKN, dissecting cellulitis of the scalp is another inflammatory hair disorder that is worsened by frequent short haircuts.⁵ Dissecting cellulitis of the scalp is a primary cicatricial alopecia proposed to be secondary to follicular occlusion. It often is seen in black males aged 20 to 40 years and is characterized by boggy suppurative nodules and cysts with draining sinus tracts, abscesses, and resultant scarring alopecia. Dissecting cellulitis of the scalp is part of the follicular occlusion tetrad, which also includes hidradenitis suppurativa, acne conglobata, and pilonidal cysts. First-line therapies include topical and oral antibiotics, topical retinoids, intralesional corticosteroids, incision and drainage of fluctuant nodules, and oral isotretinoin with or without rifampin. Alternative treatments include oral zinc supplementation, oral corticosteroids, tumor necrosis factor α inhibitors, laser therapies, radiotherapy, and surgical management with wide local excision or total scalpectomy.^6,7

Folliculitis Decalvans
Folliculitis decalvans is a primary cicatricial alopecia of the scalp that most commonly presents in middle-aged men without racial predilection.⁸ Folliculitis decalvans presents with multiple pustules, crusts, tufted hairs, and perifollicular hyperkeratosis, leading to scarring of the scalp, which often is most severe on the posterior vertex. Staphylococcus aureus is a presumed player in the pathogenesis of folliculitis decalvans with superantigens causing release of cytokines stimulating follicular destruction. Close haircuts in conformation with military grooming standards can contribute to this condition due to mechanical trauma and subsequent inflammation. It typically is diagnosed clinically, but if histologic confirmation is desired, a sample from the periphery of early lesions is preferred.⁹ Initial treatment consists of antibacterial shampoos, topical corticosteroids, topical antibiotics, and combination oral antibiotic therapy with rifampin and clindamycin. Studies using oral isotretinoin have shown variable results,^10,11 and the most effective treatment of recalcitrant lesions appears to be intralesional corticosteroids.¹²

Follicular and Scarring Disorders

In addition to inflammatory hair disorders, military grooming standards have been linked to the pathogenesis of diseases such as pseudofolliculitis barbae, traction alopecia, and keloids, specifically through irritation of the face, neck, and scalp, as well as damage to the follicular unit.⁵ These conditions develop because grooming regulations necessitate certain hair practices such as close shaving of facial and neck hair and keeping long hair secured relatively tightly to the scalp.

Pseudofolliculitis Barbae
Males in the military are obligated to keep their faces clean-shaven.¹ They may acquire a medical waiver for a specified beard length if deemed appropriate by the treating physician,¹ which often leads to the need for continual waiver renewal and also may warrant possible negative perception from peers, subordinates, and leadership. One of the most prevalent conditions that is closely associated with shaving is pseudofolliculitis barbae. The combination of close shaving and tightly coiled hairs causes the hairs to grow toward and penetrate the skin, particularly on the neck.¹³ In some cases, the hairs never actually exit the skin and simply curl within the superficial epidermis. A foreign body reaction often arises, leading to inflamed follicular papules and pustules. Affected individuals may experience pain, pruritus, and secondary infections. Postinflammatory hyperpigmentation, hypertrophic scarring, and keloid formation are common sequelae in cases of untreated disease. Pseudofolliculitis barbae also is exacerbated by pulling the skin taut and shaving against the grain, making behavioral interventions a key component in management of this condition. Preliminary recommendations include using a new or electric razor, leaving hair at least 2 mm in length, and shaving in the direction of hair growth. Other treatment options with varying effectiveness include daily alternation of a mild topical corticosteroid and one of the following: a topical retinoid, topical antibiotics, or glycolic acid. The only treatments that approach definitive cure are laser hair removal and electrolysis for which patient skin type plays an important role in laser selection.⁵

Traction Alopecia
Similar to their male counterparts, female military members must also present a conservative professional appearance, including hair that is neatly groomed.¹ If the length of the hair extends beyond the uniform collar, it must be inconspicuously fastened or pinned above the collar. As a result, loosely tied hair is unauthorized, and females with long hair must secure their hair tightly on a daily basis. Traction alopecia results from tight hairstyling over a prolonged period and commonly affects female soldiers. The etiology is presumed to be mechanical loosening of hair within the follicles, leading to inflammation. Although traditionally seen in black women along the frontal and temporal hairlines, traction alopecia has been identified in individuals of all races and can occur anywhere on the scalp.⁵ Perifollicular erythema may be the first sign, and papules and pustules may be visible. Although the hair loss in traction alopecia usually is reversible if the traction is ceased, end-stage disease may be permanent.6 Halting traction-inducing practices is paramount, and other treatment options that may slow progression include topical or oral antibiotics and topical or intralesional corticosteroids. Recovery of hair loss also may be aided by topical minoxidil.⁵

Keloids
Keloid formation is an important pathology to address, as it may result from several of the aforementioned conditions. Keloids are most commonly seen in black individuals but also can occur in Hispanic and Asian patients. The cause has not been fully elucidated but is thought to be a combination of dysfunctional fibroblasts with a genetic component based on racial predilection and twin concordance studies.⁵ The chest, shoulders, upper back, neck, and earlobes are particularly susceptible to keloid formation, which can appear from 1 to 24 years following dermal trauma.5 Unlike hypertrophic scars, keloids generally do not regress and frequently cause discomfort, pruritus, and emotional distress. They also can hinder wearing a military uniform. Sustained remission is problematic, making prevention a first-line approach, including proper care of wounds when they occur and avoiding elective procedures such as piercings and tattoos. Intralesional corticosteroids, adjuvant injections (eg, 5-fluorouracil), silicone sheeting, cryotherapy, radiation, laser therapy, and excision are some of the treatment options when keloids have formed.⁵

Final Comment

It is important to recognize military grooming standards as a cause or contributor to several diseases of the head and neck in military servicemembers. Specifically, frequent haircuts in male soldiers are associated with several inflammatory hair disorders, including AKN, dissecting cellulitis of the scalp, and folliculitis decalvans, while daily shaving predisposes individuals to pseudofolliculitis barbae with possible keloid formation. Females may develop traction alopecia from chronically tight, pulled back hairstyles. All of these conditions have health implications for the affected individuals and can compromise the military mission. Awareness, prevention, and recognition are key along with the knowledge base to provide anticipatory avoidance and initiate appropriate treatments, thereby mitigating these potential consequences.

MONTREAL—In patients hospitalized for a recent acute ischemic stroke or transient ischemic attack (TIA), a smartphone-based method identified three times more patients with atrial fibrillation than did 24-hour Holter monitoring after discharge, according to a study presented at the 11th World Stroke Congress.

This high level of atrial fibrillation detection suggests that this relatively cheap and noninvasive device is a good complement to conventional monitoring by a 24-hour Holter recording or an implanted loop recorder in patients with recent stroke. The device may thus satisfy the requirements of current guidelines from the world’s cardiology societies.

In-Hospital and Postdischarge Monitoring

In the study, 294 of 1,079 patients with acute ischemic stroke or TIA underwent serial, 30-second monitoring with the AliveCor device while hospitalized. The device was designed for smartphone-enabled ECG measurement. After discharge, the same patients underwent Holter monitoring. The latter technique identified eight patients (3%) with atrial fibrillation, compared with 25 patients (9%) who were identified using the AliveCor device, said Bernard Yan, MD, a consultant neurologist and endovascular neurointerventionist in the Comprehensive Stroke Center of the Royal Melbourne Hospital. Seven of the eight patients identified with atrial fibrillation by Holter monitoring were also found to have atrial fibrillation by the AliveCor device.

Dr. Yan attributed the higher in-hospital detection rate for atrial fibrillation to the timing of screening, which occurred within days of the stroke or TIA, rather than after the patient had left the hospital. “The difference may be because we monitored patients [with the AliveCor device] much earlier, during their hot period right after their stroke.”

Practice Does Not Match Recommendations

The trial, which was called SPOT-AF, was conducted at several centers in Australia, China, and Hong Kong. All patients underwent AliveCor monitoring during their stay in the hospital, which lasted for a median of four days. Patients performed a 30-second heart rhythm check every time a nurse saw them for a routine vital-sign examination, which usually was three or four times per day. The current analysis focused on the 294 patients (27% of the 1,079 patients) who also underwent 24-hour Holter monitoring following hospital discharge when ordered by their personal physician.

This 27% rate of postdischarge Holter monitoring was consistent with that of a 2016 review of more than 17,000 patients with stroke or TIA in Canada. That study found that 31% of participants underwent 24-hour Holter monitoring for atrial fibrillation during the 30 days following their index event. Guidelines, however, call for atrial fibrillation screening in all patients with recent ischemic stroke and TIA.

Although screening for atrial fibrillation with a smartphone-based device is inexpensive and easy, Dr. Yan did not suggest that this approach could replace a Holter monitor or an implanted loop recorder, which is what current guidelines recommend. “To change the guidelines, we need a different study that compares these approaches head to head.”

SPOT-AF received partial funding from Boehringer Ingelheim. Dr. Yan has spoken on behalf of Bayer, Boehringer Ingelheim, Pfizer, and Stryker.

—Mitchel L. Zoler 

Suggested Reading

Edwards JD, Kapral MK, Fang J, et al. Underutilization of ambulatory ECG monitoring after stroke and transient ischemic attack: missed opportunities for atrial fibrillation detection. Stroke. 2016;47(8):1982-1989.

Tu HT, Chen Z, Swift C, et al. Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack. Int J Stroke. 2017;12(7):786-789.

MONTREAL—In patients hospitalized for a recent acute ischemic stroke or transient ischemic attack (TIA), a smartphone-based method identified three times more patients with atrial fibrillation than did 24-hour Holter monitoring after discharge, according to a study presented at the 11th World Stroke Congress.

This high level of atrial fibrillation detection suggests that this relatively cheap and noninvasive device is a good complement to conventional monitoring by a 24-hour Holter recording or an implanted loop recorder in patients with recent stroke. The device may thus satisfy the requirements of current guidelines from the world’s cardiology societies.

In-Hospital and Postdischarge Monitoring

In the study, 294 of 1,079 patients with acute ischemic stroke or TIA underwent serial, 30-second monitoring with the AliveCor device while hospitalized. The device was designed for smartphone-enabled ECG measurement. After discharge, the same patients underwent Holter monitoring. The latter technique identified eight patients (3%) with atrial fibrillation, compared with 25 patients (9%) who were identified using the AliveCor device, said Bernard Yan, MD, a consultant neurologist and endovascular neurointerventionist in the Comprehensive Stroke Center of the Royal Melbourne Hospital. Seven of the eight patients identified with atrial fibrillation by Holter monitoring were also found to have atrial fibrillation by the AliveCor device.

Dr. Yan attributed the higher in-hospital detection rate for atrial fibrillation to the timing of screening, which occurred within days of the stroke or TIA, rather than after the patient had left the hospital. “The difference may be because we monitored patients [with the AliveCor device] much earlier, during their hot period right after their stroke.”

Practice Does Not Match Recommendations

The trial, which was called SPOT-AF, was conducted at several centers in Australia, China, and Hong Kong. All patients underwent AliveCor monitoring during their stay in the hospital, which lasted for a median of four days. Patients performed a 30-second heart rhythm check every time a nurse saw them for a routine vital-sign examination, which usually was three or four times per day. The current analysis focused on the 294 patients (27% of the 1,079 patients) who also underwent 24-hour Holter monitoring following hospital discharge when ordered by their personal physician.

This 27% rate of postdischarge Holter monitoring was consistent with that of a 2016 review of more than 17,000 patients with stroke or TIA in Canada. That study found that 31% of participants underwent 24-hour Holter monitoring for atrial fibrillation during the 30 days following their index event. Guidelines, however, call for atrial fibrillation screening in all patients with recent ischemic stroke and TIA.

Although screening for atrial fibrillation with a smartphone-based device is inexpensive and easy, Dr. Yan did not suggest that this approach could replace a Holter monitor or an implanted loop recorder, which is what current guidelines recommend. “To change the guidelines, we need a different study that compares these approaches head to head.”

SPOT-AF received partial funding from Boehringer Ingelheim. Dr. Yan has spoken on behalf of Bayer, Boehringer Ingelheim, Pfizer, and Stryker.

—Mitchel L. Zoler 

Suggested Reading

Edwards JD, Kapral MK, Fang J, et al. Underutilization of ambulatory ECG monitoring after stroke and transient ischemic attack: missed opportunities for atrial fibrillation detection. Stroke. 2016;47(8):1982-1989.

Tu HT, Chen Z, Swift C, et al. Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack. Int J Stroke. 2017;12(7):786-789.

MONTREAL—In patients hospitalized for a recent acute ischemic stroke or transient ischemic attack (TIA), a smartphone-based method identified three times more patients with atrial fibrillation than did 24-hour Holter monitoring after discharge, according to a study presented at the 11th World Stroke Congress.

This high level of atrial fibrillation detection suggests that this relatively cheap and noninvasive device is a good complement to conventional monitoring by a 24-hour Holter recording or an implanted loop recorder in patients with recent stroke. The device may thus satisfy the requirements of current guidelines from the world’s cardiology societies.

In-Hospital and Postdischarge Monitoring

In the study, 294 of 1,079 patients with acute ischemic stroke or TIA underwent serial, 30-second monitoring with the AliveCor device while hospitalized. The device was designed for smartphone-enabled ECG measurement. After discharge, the same patients underwent Holter monitoring. The latter technique identified eight patients (3%) with atrial fibrillation, compared with 25 patients (9%) who were identified using the AliveCor device, said Bernard Yan, MD, a consultant neurologist and endovascular neurointerventionist in the Comprehensive Stroke Center of the Royal Melbourne Hospital. Seven of the eight patients identified with atrial fibrillation by Holter monitoring were also found to have atrial fibrillation by the AliveCor device.

Dr. Yan attributed the higher in-hospital detection rate for atrial fibrillation to the timing of screening, which occurred within days of the stroke or TIA, rather than after the patient had left the hospital. “The difference may be because we monitored patients [with the AliveCor device] much earlier, during their hot period right after their stroke.”

Practice Does Not Match Recommendations

The trial, which was called SPOT-AF, was conducted at several centers in Australia, China, and Hong Kong. All patients underwent AliveCor monitoring during their stay in the hospital, which lasted for a median of four days. Patients performed a 30-second heart rhythm check every time a nurse saw them for a routine vital-sign examination, which usually was three or four times per day. The current analysis focused on the 294 patients (27% of the 1,079 patients) who also underwent 24-hour Holter monitoring following hospital discharge when ordered by their personal physician.

This 27% rate of postdischarge Holter monitoring was consistent with that of a 2016 review of more than 17,000 patients with stroke or TIA in Canada. That study found that 31% of participants underwent 24-hour Holter monitoring for atrial fibrillation during the 30 days following their index event. Guidelines, however, call for atrial fibrillation screening in all patients with recent ischemic stroke and TIA.

Although screening for atrial fibrillation with a smartphone-based device is inexpensive and easy, Dr. Yan did not suggest that this approach could replace a Holter monitor or an implanted loop recorder, which is what current guidelines recommend. “To change the guidelines, we need a different study that compares these approaches head to head.”

SPOT-AF received partial funding from Boehringer Ingelheim. Dr. Yan has spoken on behalf of Bayer, Boehringer Ingelheim, Pfizer, and Stryker.

—Mitchel L. Zoler 

Suggested Reading

Edwards JD, Kapral MK, Fang J, et al. Underutilization of ambulatory ECG monitoring after stroke and transient ischemic attack: missed opportunities for atrial fibrillation detection. Stroke. 2016;47(8):1982-1989.

Tu HT, Chen Z, Swift C, et al. Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack. Int J Stroke. 2017;12(7):786-789.

BOSTON – A new surgical option for stage IV colon cancer with isolated liver metastases is beginning to attract attention: the liver-first approach.

It’s an alternative to usual care, meaning simultaneous bowel and liver resection or bowel resection with liver surgery later on.

Systemic chemotherapy comes first, followed by liver resection. If margins are microscopically negative, the patient gets another round of chemotherapy. If no additional lesions emerge, the primary tumor is taken out. The entire process can take up to a year.

The approach was developed in the Netherlands for rectal cancer with advanced liver metastases. The idea was to get the liver lesions out before they became unresectable, then remove the primary tumor later on. It’s gaining traction now for colon cancer, and beginning to trickle into the United States at a few academic medical centers.

It comes down to what’s more dangerous, the metastases or the primary tumor? Tumor science hasn’t answered that question yet. There’s general agreement that metastases are what kill people with cancer, but it’s not known if they come mostly from previous metastases or from the primary tumor. The liver-first approach assumes the former.

M. Alexander Otto/MDedge News

Liver-first is “extremely controversial. For older surgeons who are not in tertiary care centers, liver-first doesn’t make sense, and it doesn’t seem to make sense to patients. They wonder why you would go after the liver when they were diagnosed with a colon tumor,” said Janice Rafferty, MD, FACS, professor of surgery at the University of Cincinnati, at the annual clinical congress of the American College of Surgeons.

“Well, it’s because the primary tumor doesn’t limit your life,” she continued. “The life-limiting disease is in the liver, not the colon. If you explain it to them that way, it makes sense. If we cannot get an R0 resection on the liver, it doesn’t make sense to go after the primary, unless it’s symptomatic with obstruction, bleeding, or fistula.”

There have been about 10 attempts at a randomized trial of this approach versus usual care, but they were not successful because of the difficulty of recruiting patients. Patients – and no doubt, some surgeons – may have some resistance to the logic of going after metastases first.

Dr. Rafferty moderated a review of research from Yale University, New Haven, Conn., that attempted to plug the evidence gap. The Yale investigators “presented really interesting data that shows that liver-first has improved survival,” she said.

The Yale team used the National Cancer Database to compare 2010-2015 outcomes from liver-first patients with patients who had simultaneous or bowel-first resections, followed by later liver resections. The database didn’t allow them to tease out simultaneous from bowel-first cases, so they lumped them together as usual care. To avoid confounding, rectal carcinomas and metastases to the lung, brain, and other organs were excluded.

Median survival was 34 months among 358 liver-first patients versus 24 months among 18,042 usual care patients in an intention-to-treat analysis. Among patients who completed their resections, median survival was 57 months among 140 liver-first patients versus 36 months with usual care in 3,988.

The benefit held after adjustment for patient and tumor characteristics (hazard ratio for death 0.77 in favor of liver first). When further adjusted for chemotherapy timing, there was a strong trend for liver-first but it was not statistically significant, suggesting that up-front chemotherapy contributed to the results (HR, 0.88; 95% confidence interval, 0.75-1.01; P = .09).

There were many caveats. The liver-first patients were younger, with over half under the age of 60 years versus just over 40% in usual care. They were also healthier based on Charlson comorbidity scores and more likely to have upfront chemotherapy and be treated at an academic center.

So, what should surgeons make of these findings? Lead investigator Vadim Kurbatov, MD, a Yale surgery resident, argued that, at the very least, they suggest that liver-first is a viable option for stage IV colon cancer with isolated liver metastases. Going further, they suggest that liver first may be the right way to go for younger, healthier patients at academic centers.

For sicker stage IV patients, however, the role of liver-first is unclear. “We really do need a randomized trial,” he said.

Dr. Kurbatov and Dr. Rafferty had no relevant disclosures to report. The work was funded in part by the National Institutes of Health.

[email protected]

BOSTON – A new surgical option for stage IV colon cancer with isolated liver metastases is beginning to attract attention: the liver-first approach.

It’s an alternative to usual care, meaning simultaneous bowel and liver resection or bowel resection with liver surgery later on.

Systemic chemotherapy comes first, followed by liver resection. If margins are microscopically negative, the patient gets another round of chemotherapy. If no additional lesions emerge, the primary tumor is taken out. The entire process can take up to a year.

The approach was developed in the Netherlands for rectal cancer with advanced liver metastases. The idea was to get the liver lesions out before they became unresectable, then remove the primary tumor later on. It’s gaining traction now for colon cancer, and beginning to trickle into the United States at a few academic medical centers.

It comes down to what’s more dangerous, the metastases or the primary tumor? Tumor science hasn’t answered that question yet. There’s general agreement that metastases are what kill people with cancer, but it’s not known if they come mostly from previous metastases or from the primary tumor. The liver-first approach assumes the former.

M. Alexander Otto/MDedge News

Liver-first is “extremely controversial. For older surgeons who are not in tertiary care centers, liver-first doesn’t make sense, and it doesn’t seem to make sense to patients. They wonder why you would go after the liver when they were diagnosed with a colon tumor,” said Janice Rafferty, MD, FACS, professor of surgery at the University of Cincinnati, at the annual clinical congress of the American College of Surgeons.

“Well, it’s because the primary tumor doesn’t limit your life,” she continued. “The life-limiting disease is in the liver, not the colon. If you explain it to them that way, it makes sense. If we cannot get an R0 resection on the liver, it doesn’t make sense to go after the primary, unless it’s symptomatic with obstruction, bleeding, or fistula.”

There have been about 10 attempts at a randomized trial of this approach versus usual care, but they were not successful because of the difficulty of recruiting patients. Patients – and no doubt, some surgeons – may have some resistance to the logic of going after metastases first.

Dr. Rafferty moderated a review of research from Yale University, New Haven, Conn., that attempted to plug the evidence gap. The Yale investigators “presented really interesting data that shows that liver-first has improved survival,” she said.

The Yale team used the National Cancer Database to compare 2010-2015 outcomes from liver-first patients with patients who had simultaneous or bowel-first resections, followed by later liver resections. The database didn’t allow them to tease out simultaneous from bowel-first cases, so they lumped them together as usual care. To avoid confounding, rectal carcinomas and metastases to the lung, brain, and other organs were excluded.

Median survival was 34 months among 358 liver-first patients versus 24 months among 18,042 usual care patients in an intention-to-treat analysis. Among patients who completed their resections, median survival was 57 months among 140 liver-first patients versus 36 months with usual care in 3,988.

The benefit held after adjustment for patient and tumor characteristics (hazard ratio for death 0.77 in favor of liver first). When further adjusted for chemotherapy timing, there was a strong trend for liver-first but it was not statistically significant, suggesting that up-front chemotherapy contributed to the results (HR, 0.88; 95% confidence interval, 0.75-1.01; P = .09).

There were many caveats. The liver-first patients were younger, with over half under the age of 60 years versus just over 40% in usual care. They were also healthier based on Charlson comorbidity scores and more likely to have upfront chemotherapy and be treated at an academic center.

So, what should surgeons make of these findings? Lead investigator Vadim Kurbatov, MD, a Yale surgery resident, argued that, at the very least, they suggest that liver-first is a viable option for stage IV colon cancer with isolated liver metastases. Going further, they suggest that liver first may be the right way to go for younger, healthier patients at academic centers.

For sicker stage IV patients, however, the role of liver-first is unclear. “We really do need a randomized trial,” he said.

Dr. Kurbatov and Dr. Rafferty had no relevant disclosures to report. The work was funded in part by the National Institutes of Health.

[email protected]

BOSTON – A new surgical option for stage IV colon cancer with isolated liver metastases is beginning to attract attention: the liver-first approach.

It’s an alternative to usual care, meaning simultaneous bowel and liver resection or bowel resection with liver surgery later on.

Systemic chemotherapy comes first, followed by liver resection. If margins are microscopically negative, the patient gets another round of chemotherapy. If no additional lesions emerge, the primary tumor is taken out. The entire process can take up to a year.

The approach was developed in the Netherlands for rectal cancer with advanced liver metastases. The idea was to get the liver lesions out before they became unresectable, then remove the primary tumor later on. It’s gaining traction now for colon cancer, and beginning to trickle into the United States at a few academic medical centers.

It comes down to what’s more dangerous, the metastases or the primary tumor? Tumor science hasn’t answered that question yet. There’s general agreement that metastases are what kill people with cancer, but it’s not known if they come mostly from previous metastases or from the primary tumor. The liver-first approach assumes the former.

M. Alexander Otto/MDedge News

Liver-first is “extremely controversial. For older surgeons who are not in tertiary care centers, liver-first doesn’t make sense, and it doesn’t seem to make sense to patients. They wonder why you would go after the liver when they were diagnosed with a colon tumor,” said Janice Rafferty, MD, FACS, professor of surgery at the University of Cincinnati, at the annual clinical congress of the American College of Surgeons.

“Well, it’s because the primary tumor doesn’t limit your life,” she continued. “The life-limiting disease is in the liver, not the colon. If you explain it to them that way, it makes sense. If we cannot get an R0 resection on the liver, it doesn’t make sense to go after the primary, unless it’s symptomatic with obstruction, bleeding, or fistula.”

There have been about 10 attempts at a randomized trial of this approach versus usual care, but they were not successful because of the difficulty of recruiting patients. Patients – and no doubt, some surgeons – may have some resistance to the logic of going after metastases first.

Dr. Rafferty moderated a review of research from Yale University, New Haven, Conn., that attempted to plug the evidence gap. The Yale investigators “presented really interesting data that shows that liver-first has improved survival,” she said.

The Yale team used the National Cancer Database to compare 2010-2015 outcomes from liver-first patients with patients who had simultaneous or bowel-first resections, followed by later liver resections. The database didn’t allow them to tease out simultaneous from bowel-first cases, so they lumped them together as usual care. To avoid confounding, rectal carcinomas and metastases to the lung, brain, and other organs were excluded.

Median survival was 34 months among 358 liver-first patients versus 24 months among 18,042 usual care patients in an intention-to-treat analysis. Among patients who completed their resections, median survival was 57 months among 140 liver-first patients versus 36 months with usual care in 3,988.

The benefit held after adjustment for patient and tumor characteristics (hazard ratio for death 0.77 in favor of liver first). When further adjusted for chemotherapy timing, there was a strong trend for liver-first but it was not statistically significant, suggesting that up-front chemotherapy contributed to the results (HR, 0.88; 95% confidence interval, 0.75-1.01; P = .09).

There were many caveats. The liver-first patients were younger, with over half under the age of 60 years versus just over 40% in usual care. They were also healthier based on Charlson comorbidity scores and more likely to have upfront chemotherapy and be treated at an academic center.

So, what should surgeons make of these findings? Lead investigator Vadim Kurbatov, MD, a Yale surgery resident, argued that, at the very least, they suggest that liver-first is a viable option for stage IV colon cancer with isolated liver metastases. Going further, they suggest that liver first may be the right way to go for younger, healthier patients at academic centers.

For sicker stage IV patients, however, the role of liver-first is unclear. “We really do need a randomized trial,” he said.

Dr. Kurbatov and Dr. Rafferty had no relevant disclosures to report. The work was funded in part by the National Institutes of Health.

[email protected]

Tinea incognito (TI) describes a dermatophytosis with often atypical clinical features attributed to prior use of topical corticosteroids or other immunomodulating agents. Tinea incognito may lack the scale and elevated margin typical of cutaneous dermatophytoses and can be mistaken for other pediatric cutaneous diseases, particularly atopic dermatitis. ¹ Given the prevalence of TI and its susceptibility to misdiagnosis, we conducted a retrospective medical record review of cases of pediatric dermatophytosis presenting from 2005 to 2016.

Methods

We reviewed medical records for patients younger than 18 years who had been seen at the Faculty Group Practice of the Ronald O. Perelman Department of Dermatology, New York University School of Medicine (New York, New York), between January 1, 2005, and October 21, 2016, using International Classification of Diseases, Ninth Revision (ICD-9) codes 110.0 (tinea capitis), 110.1 (onychomycosis/tinea unguium), 110.3 (tinea cruris), 110.4 (tinea pedis), 110.5 (tinea corporis), and 110.9 (tinea, unspecified site). Cases were included in this study if there was documentation of dermatophytosis previously treated with topical corticosteroids or calcineurin inhibitors as well as positive potassium hydroxide (KOH) preparation or fungal culture with dermatophyte growth obtained from lesions satisfying the first criterion. This study was approved by the New York University School of Medicine institutional review board (study no. S15-01388).

Statistical analyses were conducted in SPSS 19.0 for Windows. Categorical variables were assessed using the χ² test for independence and the Fisher exact test.

Results

A total of 464 cases were reviewed. A positive KOH preparation or dermatophyte fungal culture was documented in 83 cases. Of them, 29 (34.9%) were treated with topical steroids and/or calcineurin inhibitors prior to presentation to dermatology (Table). The mean age at presentation was 8 years. Duration of symptoms prior to presentation was recorded for 23 of 29 patients (79.3%). Of them, 6 (26.1%) experienced symptoms for 1 month or less, 12 (52.2%) for 1 to 6 months, and 5 (21.7%) for 6 months to 1 year.

Physical examination findings (Figure) were documented in all 29 cases. Annular lesions were noted in 24 patients (82.8%). Pustules were present in 5 patients (17.2%) and papules in 11 patients (37.9%). Fourteen patients (48.3%) had involvement of the face, 14 (48.3%) of the body (ie, trunk, extremities, or groin), and 3 (10.3%) of the scalp. Six patients (20.7%) demonstrated findings at more than one body site.

Females were more likely to demonstrate facial lesions (P=.02), while males were more likely to present with body lesions (P=.04). Of 26 patients diagnosed via fungal culture, 16 (55.2%) grew Trichophyton tonsurans, 4 (13.8%) grew Trichophyton rubrum, 3 (10.3%) grew Trichophyton mentagrophytes, 2 (6.9%) grew Microsporum canis, and 1 (3.4%) grew Microsporum gypseum. Treatment entailed oral medication in 18 cases (62.1%). Of them, 13 (72.2%) were treated with griseofulvin, 3 (16.7%) with fluconazole, and 2 (11.1%) with terbinafine. Topical antifungals were prescribed in the remaining 11 cases (37.9%); no further treatment was documented.

Comment

Since the initial description of TI, approximately 60 case reports and small series as well as several larger observational studies describing TI have been published. In our series of pediatric patients, 29 of 83 culture- or KOH-confirmed dermatophytosis cases (34.9%) were considered to be TI due to treatment with topical corticosteroids and/or calcineurin inhibitors prior to presentation. This high prevalence contrasts with the 5.6% prevalence reported in the only prior large case series examining TI in childhood.² These authors further reported that in their pediatric population, TI was significantly (odds ratio, 8.7; 95% CI, 4.7-16.1) more likely to occur on the face relative to other dermatophytoses and significantly (odds ratio, 0.014; 95% CI, 0.002-0.099) less likely to occur on the scalp.² We noted a significant association between female gender and facial symptoms as well as between male gender and truncal symptoms. Taken together, these findings suggest an increased likelihood of pediatric tinea faciei to be inappropriately treated, particularly in females.

Although TI treated with topical corticosteroids or calcineurin inhibitors can mimic other skin diseases, a majority of patients in our series demonstrated findings associated with classic tinea, such as annularity and scale. Further, we found that T tonsurans was the causative organism in most cases with T rubrum uncommonly seen, though it is the most prevalent dermatophyte observed worldwide and in 2 large TI case series.^3,4 Regional variation in dermatophytes may account for these differences. In our study, griseofulvin was used most frequently in TI treatment, though a systematic review of oral antifungals in tinea capitis supported terbinafine’s greater efficacy in patients infected with T tonsurans.⁵

Conclusion

Our case series demonstrated a 35% prevalence of TI cases in a population of children with confirmed dermatophytosis presenting to dermatologists at an American academic medical center. We hope that noting the high prevalence and manifold presentations of this disease will aid practitioners in maintaining clinical suspicion for dermatophytosis and thereby facilitate appropriate identification and treatment of TI.

Tinea incognito (TI) describes a dermatophytosis with often atypical clinical features attributed to prior use of topical corticosteroids or other immunomodulating agents. Tinea incognito may lack the scale and elevated margin typical of cutaneous dermatophytoses and can be mistaken for other pediatric cutaneous diseases, particularly atopic dermatitis. ¹ Given the prevalence of TI and its susceptibility to misdiagnosis, we conducted a retrospective medical record review of cases of pediatric dermatophytosis presenting from 2005 to 2016.

Methods

We reviewed medical records for patients younger than 18 years who had been seen at the Faculty Group Practice of the Ronald O. Perelman Department of Dermatology, New York University School of Medicine (New York, New York), between January 1, 2005, and October 21, 2016, using International Classification of Diseases, Ninth Revision (ICD-9) codes 110.0 (tinea capitis), 110.1 (onychomycosis/tinea unguium), 110.3 (tinea cruris), 110.4 (tinea pedis), 110.5 (tinea corporis), and 110.9 (tinea, unspecified site). Cases were included in this study if there was documentation of dermatophytosis previously treated with topical corticosteroids or calcineurin inhibitors as well as positive potassium hydroxide (KOH) preparation or fungal culture with dermatophyte growth obtained from lesions satisfying the first criterion. This study was approved by the New York University School of Medicine institutional review board (study no. S15-01388).

Statistical analyses were conducted in SPSS 19.0 for Windows. Categorical variables were assessed using the χ² test for independence and the Fisher exact test.

Results

A total of 464 cases were reviewed. A positive KOH preparation or dermatophyte fungal culture was documented in 83 cases. Of them, 29 (34.9%) were treated with topical steroids and/or calcineurin inhibitors prior to presentation to dermatology (Table). The mean age at presentation was 8 years. Duration of symptoms prior to presentation was recorded for 23 of 29 patients (79.3%). Of them, 6 (26.1%) experienced symptoms for 1 month or less, 12 (52.2%) for 1 to 6 months, and 5 (21.7%) for 6 months to 1 year.

Physical examination findings (Figure) were documented in all 29 cases. Annular lesions were noted in 24 patients (82.8%). Pustules were present in 5 patients (17.2%) and papules in 11 patients (37.9%). Fourteen patients (48.3%) had involvement of the face, 14 (48.3%) of the body (ie, trunk, extremities, or groin), and 3 (10.3%) of the scalp. Six patients (20.7%) demonstrated findings at more than one body site.

Females were more likely to demonstrate facial lesions (P=.02), while males were more likely to present with body lesions (P=.04). Of 26 patients diagnosed via fungal culture, 16 (55.2%) grew Trichophyton tonsurans, 4 (13.8%) grew Trichophyton rubrum, 3 (10.3%) grew Trichophyton mentagrophytes, 2 (6.9%) grew Microsporum canis, and 1 (3.4%) grew Microsporum gypseum. Treatment entailed oral medication in 18 cases (62.1%). Of them, 13 (72.2%) were treated with griseofulvin, 3 (16.7%) with fluconazole, and 2 (11.1%) with terbinafine. Topical antifungals were prescribed in the remaining 11 cases (37.9%); no further treatment was documented.

Comment

Since the initial description of TI, approximately 60 case reports and small series as well as several larger observational studies describing TI have been published. In our series of pediatric patients, 29 of 83 culture- or KOH-confirmed dermatophytosis cases (34.9%) were considered to be TI due to treatment with topical corticosteroids and/or calcineurin inhibitors prior to presentation. This high prevalence contrasts with the 5.6% prevalence reported in the only prior large case series examining TI in childhood.² These authors further reported that in their pediatric population, TI was significantly (odds ratio, 8.7; 95% CI, 4.7-16.1) more likely to occur on the face relative to other dermatophytoses and significantly (odds ratio, 0.014; 95% CI, 0.002-0.099) less likely to occur on the scalp.² We noted a significant association between female gender and facial symptoms as well as between male gender and truncal symptoms. Taken together, these findings suggest an increased likelihood of pediatric tinea faciei to be inappropriately treated, particularly in females.

Although TI treated with topical corticosteroids or calcineurin inhibitors can mimic other skin diseases, a majority of patients in our series demonstrated findings associated with classic tinea, such as annularity and scale. Further, we found that T tonsurans was the causative organism in most cases with T rubrum uncommonly seen, though it is the most prevalent dermatophyte observed worldwide and in 2 large TI case series.^3,4 Regional variation in dermatophytes may account for these differences. In our study, griseofulvin was used most frequently in TI treatment, though a systematic review of oral antifungals in tinea capitis supported terbinafine’s greater efficacy in patients infected with T tonsurans.⁵

Conclusion

Our case series demonstrated a 35% prevalence of TI cases in a population of children with confirmed dermatophytosis presenting to dermatologists at an American academic medical center. We hope that noting the high prevalence and manifold presentations of this disease will aid practitioners in maintaining clinical suspicion for dermatophytosis and thereby facilitate appropriate identification and treatment of TI.

Tinea incognito (TI) describes a dermatophytosis with often atypical clinical features attributed to prior use of topical corticosteroids or other immunomodulating agents. Tinea incognito may lack the scale and elevated margin typical of cutaneous dermatophytoses and can be mistaken for other pediatric cutaneous diseases, particularly atopic dermatitis. ¹ Given the prevalence of TI and its susceptibility to misdiagnosis, we conducted a retrospective medical record review of cases of pediatric dermatophytosis presenting from 2005 to 2016.

Methods

We reviewed medical records for patients younger than 18 years who had been seen at the Faculty Group Practice of the Ronald O. Perelman Department of Dermatology, New York University School of Medicine (New York, New York), between January 1, 2005, and October 21, 2016, using International Classification of Diseases, Ninth Revision (ICD-9) codes 110.0 (tinea capitis), 110.1 (onychomycosis/tinea unguium), 110.3 (tinea cruris), 110.4 (tinea pedis), 110.5 (tinea corporis), and 110.9 (tinea, unspecified site). Cases were included in this study if there was documentation of dermatophytosis previously treated with topical corticosteroids or calcineurin inhibitors as well as positive potassium hydroxide (KOH) preparation or fungal culture with dermatophyte growth obtained from lesions satisfying the first criterion. This study was approved by the New York University School of Medicine institutional review board (study no. S15-01388).

Statistical analyses were conducted in SPSS 19.0 for Windows. Categorical variables were assessed using the χ² test for independence and the Fisher exact test.

Results

A total of 464 cases were reviewed. A positive KOH preparation or dermatophyte fungal culture was documented in 83 cases. Of them, 29 (34.9%) were treated with topical steroids and/or calcineurin inhibitors prior to presentation to dermatology (Table). The mean age at presentation was 8 years. Duration of symptoms prior to presentation was recorded for 23 of 29 patients (79.3%). Of them, 6 (26.1%) experienced symptoms for 1 month or less, 12 (52.2%) for 1 to 6 months, and 5 (21.7%) for 6 months to 1 year.

Physical examination findings (Figure) were documented in all 29 cases. Annular lesions were noted in 24 patients (82.8%). Pustules were present in 5 patients (17.2%) and papules in 11 patients (37.9%). Fourteen patients (48.3%) had involvement of the face, 14 (48.3%) of the body (ie, trunk, extremities, or groin), and 3 (10.3%) of the scalp. Six patients (20.7%) demonstrated findings at more than one body site.

Females were more likely to demonstrate facial lesions (P=.02), while males were more likely to present with body lesions (P=.04). Of 26 patients diagnosed via fungal culture, 16 (55.2%) grew Trichophyton tonsurans, 4 (13.8%) grew Trichophyton rubrum, 3 (10.3%) grew Trichophyton mentagrophytes, 2 (6.9%) grew Microsporum canis, and 1 (3.4%) grew Microsporum gypseum. Treatment entailed oral medication in 18 cases (62.1%). Of them, 13 (72.2%) were treated with griseofulvin, 3 (16.7%) with fluconazole, and 2 (11.1%) with terbinafine. Topical antifungals were prescribed in the remaining 11 cases (37.9%); no further treatment was documented.

Comment

Since the initial description of TI, approximately 60 case reports and small series as well as several larger observational studies describing TI have been published. In our series of pediatric patients, 29 of 83 culture- or KOH-confirmed dermatophytosis cases (34.9%) were considered to be TI due to treatment with topical corticosteroids and/or calcineurin inhibitors prior to presentation. This high prevalence contrasts with the 5.6% prevalence reported in the only prior large case series examining TI in childhood.² These authors further reported that in their pediatric population, TI was significantly (odds ratio, 8.7; 95% CI, 4.7-16.1) more likely to occur on the face relative to other dermatophytoses and significantly (odds ratio, 0.014; 95% CI, 0.002-0.099) less likely to occur on the scalp.² We noted a significant association between female gender and facial symptoms as well as between male gender and truncal symptoms. Taken together, these findings suggest an increased likelihood of pediatric tinea faciei to be inappropriately treated, particularly in females.

Although TI treated with topical corticosteroids or calcineurin inhibitors can mimic other skin diseases, a majority of patients in our series demonstrated findings associated with classic tinea, such as annularity and scale. Further, we found that T tonsurans was the causative organism in most cases with T rubrum uncommonly seen, though it is the most prevalent dermatophyte observed worldwide and in 2 large TI case series.^3,4 Regional variation in dermatophytes may account for these differences. In our study, griseofulvin was used most frequently in TI treatment, though a systematic review of oral antifungals in tinea capitis supported terbinafine’s greater efficacy in patients infected with T tonsurans.⁵

Conclusion

Our case series demonstrated a 35% prevalence of TI cases in a population of children with confirmed dermatophytosis presenting to dermatologists at an American academic medical center. We hope that noting the high prevalence and manifold presentations of this disease will aid practitioners in maintaining clinical suspicion for dermatophytosis and thereby facilitate appropriate identification and treatment of TI.