A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

A version of this article first appeared on Medscape.com.

A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

A version of this article first appeared on Medscape.com.

A high-fiber diet may improve treatment response among patients with advanced melanoma receiving immune checkpoint inhibitors, while probiotics may reduce treatment effectiveness, a new study shows.

Investigators found that the patients who reported consuming at least 20 g of dietary fiber daily had significantly better progression-free survival (PFS) than those who reported consuming lower amounts of dietary fiber. However, patients who took a probiotic supplement in the past month had slightly shorter PFS, but the results were not statistically significant.

And after adjusting for clinical factors, each 5-g increase in daily dietary fiber intake corresponded to a 30% lower risk of disease progression, according to the analysis, published online Dec. 23, 2021, in Science.

“Our study sheds light on the potential effects of a patient’s diet and supplement use when starting treatment with immune checkpoint blockade,” co–lead study author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at University of Texas MD Anderson Cancer Center, Houston, said in a press release. “These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies.”

Previous research has suggested that the microbiome can influence patients’ response to immunotherapy. One recent analysis, for instance, found that fecal microbiota transplant can improve response to immunotherapy in advanced melanoma. And a small 2019 analysis from Dr. Dr. Wargo and colleagues hinted that a high-fiber diet may enhance patients’ ability to respond to immunotherapy in advanced melanoma, while probiotics appear to dampen that response.

Still, the role diet and probiotic supplements play in treatment response remains poorly understood.

In the current study, Dr. Wargo and colleagues assessed fecal microbiota profiles and dietary habits, including fiber intake and probiotic use, in 158 patients with advanced melanoma who received immune checkpoint blockade inhibitors.

In the cohort, 31% (49 of 158) of late-stage melanoma patients reported taking a commercially available probiotic in the past month. When assessing whether probiotic use influenced patient outcomes, the investigators observed a shorter but not statistically significant difference in PFS in those who took a probiotic (median, 17 months) versus those who did not (23 months).

Higher dietary fiber, however, was associated with significantly improved PFS in a subset of 128 patients. The team divided patients into a higher-fiber intake group (those consuming at least 20 g/day) and a low-fiber group (those consuming less than 20 g).

The 37 patients reporting higher fiber intake demonstrated improved PFS, compared with those in the low-intake group (median PFS not reached vs. 13 months), plus a 30% lower risk of disease progression or death for each additional 5 g consumed each day.

“The observed protective effect of dietary fiber intake in relation to PFS and response remained consistent among the subset of patients treated with anti–PD-1 monotherapy, with the exclusion of patients reporting recent antibiotic use,” the authors noted.

When assessing fiber and probiotic intake together, the researchers found that immunotherapy response rate was higher (82%) in the 22 patients who reported sufficient dietary fiber intake with no probiotic use versus 59% in 101 patients who reported either insufficient fiber intake or probiotic use.

Overall, the research suggests that “consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy,” co–lead author Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in the National Cancer Institute’s Center for Cancer Research, Bethesda, Md., said in a press statement. “The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

The investigators also explored whether dietary fiber intake enhanced treatment response in preclinical mouse models of melanoma. In this instance, mice receiving a fiber-rich diet showed delayed tumor growth after anti–PD-1 treatment, compared with mice given a low-fiber diet or probiotics.

According to the authors, “our preclinical models support the hypothesis that dietary fiber and probiotics modulate the microbiome and that antitumor immunity is impaired in mice receiving a low-fiber diet and in those receiving probiotics – with suppression of intratumoral [interferon-gamma] T-cell responses in both cases.”

Dietary fiber may exert beneficial effect by increasing specific types of bacteria in the gut, such as Ruminococcaceae, which “produce high levels of certain short-chain fatty acids that have an antitumor effect,” Dr. Trinchieri explained.

However, “the impact of dietary fiber and probiotics on the gut microbiota is only part of the bigger picture,” Dr. Trinchieri said in a press release. “Many factors can affect the ability of a patient with melanoma to respond to immunotherapy” but, according to this analysis, “the microbiota seems to be one of the dominant factors.”

While Jeffrey S. Weber, MD, PhD, applauded the “innovative and interesting” research, he believes the patient population is too small to confirm that a high-fiber diet does indeed contribute to improved immunotherapy response and PFS in patients with advanced melanoma.

Additional data are needed to clarify these findings. “I will believe it if I could see it replicated in a larger study,” Dr. Weber, professor and deputy director of the Laura and Isaac Perlmutter Cancer Center, New York University, said in an interview.

Dr. Wargo noted that a randomized clinical trial exploring how diets with varying fiber content affect the microbiome and immune response is currently enrolling patients with stage III and IV melanoma receiving immunotherapy.

This study was supported by the Melanoma Moon Shot, among others. Dr. Wargo is a collaborator on a U.S. patent application that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. Dr. Weber reported relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech BioOncology, Merck, Novartis, EMD Serono, Celldex, CytomX, Nektar, Roche, Altor, Daiichi Sankyo, and Eli Lilly, and is named on patents filed for biomarkers for ipilimumab and nivolumab.

A version of this article first appeared on Medscape.com.

Booster shot protection against symptomatic COVID-19 caused by the Omicron variant appears to fade in about 10 weeks, according to new data from Britain.

U.K. health officials shared the data just before Christmas and noted that there haven’t been enough severe cases of the Omicron variant to calculate how well boosters protect against severe disease. But they believe the extra shots provide significant protection against hospitalization and death.

“It will be a few weeks before effectiveness against severe disease with Omicron can be estimated,” U.K. Health Security Agency officials wrote in the report. “However, based on experience with previous variants, this is likely to be substantially higher than the estimates against symptomatic disease.”

Since countries began reporting Omicron cases in November, multiple studies have suggested the variant is better at escaping antibodies from vaccination and previous infection, according to the New York Times. The U.K. report adds to that, noting that both the initial vaccine series and booster doses were less effective and faded faster against the Omicron variant than the Delta variant.

Among those who received two doses of the AstraZeneca vaccine, a booster of the Pfizer or Moderna vaccine was 60% effective at preventing symptomatic disease 2 to 4 weeks after the shot. But after 10 weeks, the Pfizer booster was 35% effective, and the Moderna booster was 45% effective. (The AstraZeneca vaccine is not authorized in the United States, but the Johnson & Johnson shot uses a similar technology, the New York Times reported.)

Among those who received three Pfizer doses, vaccine effectiveness was 70% about a week after the booster but dropped to 45% after 10 weeks. At the same time, those who received an initial two-dose series of the Pfizer vaccine and then a Moderna booster seemed to have 75% effectiveness up to 9 weeks.

The report was based on an analysis of 148,000 Delta cases and 68,000 Omicron cases in the United Kingdom through Dec. 20. So far, the U.K. health officials wrote, Omicron infections appear to be less severe and less likely to lead to hospitalization than Delta infections. At that time, 132 people with lab-confirmed Omicron had been admitted to hospitals, and 14 deaths had been reported among ages 52-96.

“This analysis is preliminary because of the small numbers of Omicron cases currently in hospital and the limited spread of Omicron into older age groups as yet,” the report said.

The reinfection rate has also increased for the Omicron variant, the report found. Among the 116,000 people who had an Omicron infection, about 11,000 -- or 9.5% -- were linked to a previously confirmed infection, which is likely an undercount of reinfections. In the data analyzed, 69 Omicron cases were a third episode of COVID-19 infection, and 290 cases occurred 60-89 days after a first infection.

A version of this article first appeared on WebMD.com.

Booster shot protection against symptomatic COVID-19 caused by the Omicron variant appears to fade in about 10 weeks, according to new data from Britain.

U.K. health officials shared the data just before Christmas and noted that there haven’t been enough severe cases of the Omicron variant to calculate how well boosters protect against severe disease. But they believe the extra shots provide significant protection against hospitalization and death.

“It will be a few weeks before effectiveness against severe disease with Omicron can be estimated,” U.K. Health Security Agency officials wrote in the report. “However, based on experience with previous variants, this is likely to be substantially higher than the estimates against symptomatic disease.”

Since countries began reporting Omicron cases in November, multiple studies have suggested the variant is better at escaping antibodies from vaccination and previous infection, according to the New York Times. The U.K. report adds to that, noting that both the initial vaccine series and booster doses were less effective and faded faster against the Omicron variant than the Delta variant.

Among those who received two doses of the AstraZeneca vaccine, a booster of the Pfizer or Moderna vaccine was 60% effective at preventing symptomatic disease 2 to 4 weeks after the shot. But after 10 weeks, the Pfizer booster was 35% effective, and the Moderna booster was 45% effective. (The AstraZeneca vaccine is not authorized in the United States, but the Johnson & Johnson shot uses a similar technology, the New York Times reported.)

Among those who received three Pfizer doses, vaccine effectiveness was 70% about a week after the booster but dropped to 45% after 10 weeks. At the same time, those who received an initial two-dose series of the Pfizer vaccine and then a Moderna booster seemed to have 75% effectiveness up to 9 weeks.

The report was based on an analysis of 148,000 Delta cases and 68,000 Omicron cases in the United Kingdom through Dec. 20. So far, the U.K. health officials wrote, Omicron infections appear to be less severe and less likely to lead to hospitalization than Delta infections. At that time, 132 people with lab-confirmed Omicron had been admitted to hospitals, and 14 deaths had been reported among ages 52-96.

“This analysis is preliminary because of the small numbers of Omicron cases currently in hospital and the limited spread of Omicron into older age groups as yet,” the report said.

The reinfection rate has also increased for the Omicron variant, the report found. Among the 116,000 people who had an Omicron infection, about 11,000 -- or 9.5% -- were linked to a previously confirmed infection, which is likely an undercount of reinfections. In the data analyzed, 69 Omicron cases were a third episode of COVID-19 infection, and 290 cases occurred 60-89 days after a first infection.

A version of this article first appeared on WebMD.com.

Booster shot protection against symptomatic COVID-19 caused by the Omicron variant appears to fade in about 10 weeks, according to new data from Britain.

U.K. health officials shared the data just before Christmas and noted that there haven’t been enough severe cases of the Omicron variant to calculate how well boosters protect against severe disease. But they believe the extra shots provide significant protection against hospitalization and death.

“It will be a few weeks before effectiveness against severe disease with Omicron can be estimated,” U.K. Health Security Agency officials wrote in the report. “However, based on experience with previous variants, this is likely to be substantially higher than the estimates against symptomatic disease.”

Since countries began reporting Omicron cases in November, multiple studies have suggested the variant is better at escaping antibodies from vaccination and previous infection, according to the New York Times. The U.K. report adds to that, noting that both the initial vaccine series and booster doses were less effective and faded faster against the Omicron variant than the Delta variant.

Among those who received two doses of the AstraZeneca vaccine, a booster of the Pfizer or Moderna vaccine was 60% effective at preventing symptomatic disease 2 to 4 weeks after the shot. But after 10 weeks, the Pfizer booster was 35% effective, and the Moderna booster was 45% effective. (The AstraZeneca vaccine is not authorized in the United States, but the Johnson & Johnson shot uses a similar technology, the New York Times reported.)

Among those who received three Pfizer doses, vaccine effectiveness was 70% about a week after the booster but dropped to 45% after 10 weeks. At the same time, those who received an initial two-dose series of the Pfizer vaccine and then a Moderna booster seemed to have 75% effectiveness up to 9 weeks.

The report was based on an analysis of 148,000 Delta cases and 68,000 Omicron cases in the United Kingdom through Dec. 20. So far, the U.K. health officials wrote, Omicron infections appear to be less severe and less likely to lead to hospitalization than Delta infections. At that time, 132 people with lab-confirmed Omicron had been admitted to hospitals, and 14 deaths had been reported among ages 52-96.

“This analysis is preliminary because of the small numbers of Omicron cases currently in hospital and the limited spread of Omicron into older age groups as yet,” the report said.

The reinfection rate has also increased for the Omicron variant, the report found. Among the 116,000 people who had an Omicron infection, about 11,000 -- or 9.5% -- were linked to a previously confirmed infection, which is likely an undercount of reinfections. In the data analyzed, 69 Omicron cases were a third episode of COVID-19 infection, and 290 cases occurred 60-89 days after a first infection.

A version of this article first appeared on WebMD.com.

Repetitive behaviors towards the body, such as hair pulling and skin picking, are common. Approximately 5% of the general population may meet criteria for trichotillomania or excoriation disorder, in which the repetitive behaviors are excessive and impairing. The category of body-focused repetitive behaviors (BFRBs) extends beyond these 2 disorders to include onychophagia (nail biting), onychotillomania (nail picking), and lip or cheek chewing, which in DSM-5 are categorized under Other Specified Obsessive-Compulsive Disorder—BFRB. Of particular concern are trichophagia or dermatophagia, the ritualizing and eating of skin or hair that can lead to gastrointestinal complications.¹

The prevalence and associated distress from BFRBs have spurred increased research into psychotherapeutic interventions to remediate suffering and curb bodily damage. Under the broader umbrella of behavioral therapy or cognitive-behavioral therapy, the Expert Consensus Treatment Guidelines from the TLC Foundation² describe habit reversal therapy, comprehensive behavioral treatment, and behavioral therapy that is enhanced by acceptance and commitment therapy or dialectical behavioral therapy (DBT) skills. (Although these guidelines also summarize possible pharmacologic interventions, medication for patients with BFRBs is not discussed in this article.)

Understanding the antecedents and consequences of these recurrent behaviors is a key aspect of psychotherapeutic treatments because diverse contingencies reinforce these repetitive behaviors. As with any comprehensive assessment, asking questions to understand the function of the behaviors guides personalized treatment recommendations or referrals. Mansueto et al³ described a systematic approach to assessing BFRBs. Asking questions based on these researchers’ SCAMP domains (Sensory, Cognitive, Affective, Motor, Place) can provide patients and clinicians with a clear picture of pulling, picking, or other repetitive behaviors.
 

Sensory. Start with an assessment of how sensory experiences might play into the cycle. Questions might include: Does the patient see a distinctive hair (eg, color, texture) or skin irregularity that draws them into the behavior? Do they visually inspect the hair or skin before, during, or after? Do they describe a premonitory sensation, such as an itch? Do they have a dermatologic condition that cues interoceptive hypervigilance? Do they taste or smell the scab, excoriate, or hair? Are they particularly attuned to the auditory experiences of the process (ie, hearing the pop or a pull)? Could any substances or medications be impacting the body’s restlessness?

Cognitive. Just as we assess common automatic thoughts associated with other psychopathologies, it is important to appreciate the cognitions that occur during this behavioral chain. Some thoughts involve an intolerance of imperfection: “That hair looks different. I have to remove it.” “It is important for pores to be completely clean.” Other thoughts may involve granting permission: “I’ll just pull one.” “It has been a long week so I deserve to do just this one.” Certainly, many patients may be thinking about other daily stressors, such as occupational or interpersonal difficulties. Knowing about the patient’s mental state throughout the BFRB can guide a clinician to recommend treatment focused on (for example) cognitive-behavioral therapy for perfectionism or approaches to address existing stressors. 

Affective. One common assumption is that patients who engage in BFRBs are anxious. While it certainly may be the case, an array of affective states may accompany the repetitive behavior. Patients may describe feeling tense, bored, sad, anxious, excited, relieved, agitated, guilty, worried, or ashamed. It is typically helpful to inquire about affect before, during, and after. Knowing the emotional experiences during and outside of BFRBs can call attention to possible comorbidities that warrant treatment, such as a mood or anxiety disorder. Additionally, dysregulation in affective states during the BFRB may point to useful adjunctive skills, such as DBT. 

Motor. Some patients describe being quite unaware of their BFRB (often called “automatic”), whereas for other patients pulling or picking may be directed and within awareness (often called “focused”). It is common for patients to have both automatic and focused behaviors. Questions to understand the motor experience include: Is the patient operating on autopilot when they are engaged in the behavior? Does the behavior occur more often in certain postures, such as when they are seated or lying in bed? Understanding the choreography of the BFRB can help in determining physical barriers to protect the skin or hair. 

Place. Finally, ask the patient if they believe certain locations increase the occurrence of the BFRB. For instance, some patients may notice the behavior is more likely to occur in the bathroom or bedroom. Bathrooms often contain implements associated with these behaviors, including mirrors, tweezers, or bright lights. Knowing where the BFRB is most likely to occur can help the clinician develop planning strategies to minimize behavioral engagement. An example is a patient who is more likely to pull or pick on a long commute from work. Planning to have a hat and sweater in their vehicle for the drive home may serve as a deterrent and break the cycle. When considering the place, it may also be helpful to ask about the time of day and presence of others.

Gathering information from the SCAMP domains can lead to individualized approaches to care. Of course, nonsuicidal self-injury, delusional parasitosis, or body dysmorphic disorder are a few of the many differential diagnoses that should be considered during the assessment. After a detailed assessment, clinicians can proceed by collaboratively developing strategies with the patient, referring them to a clinician who specializes in treating BFRBs using a resource such as the TLC Foundation’s Find a Therapist directory (https://www.bfrb.org/find-help-support/find-a-therapist), or recommending a self-guided resource such as StopPulling.com or StopPicking.com.

Repetitive behaviors towards the body, such as hair pulling and skin picking, are common. Approximately 5% of the general population may meet criteria for trichotillomania or excoriation disorder, in which the repetitive behaviors are excessive and impairing. The category of body-focused repetitive behaviors (BFRBs) extends beyond these 2 disorders to include onychophagia (nail biting), onychotillomania (nail picking), and lip or cheek chewing, which in DSM-5 are categorized under Other Specified Obsessive-Compulsive Disorder—BFRB. Of particular concern are trichophagia or dermatophagia, the ritualizing and eating of skin or hair that can lead to gastrointestinal complications.¹

The prevalence and associated distress from BFRBs have spurred increased research into psychotherapeutic interventions to remediate suffering and curb bodily damage. Under the broader umbrella of behavioral therapy or cognitive-behavioral therapy, the Expert Consensus Treatment Guidelines from the TLC Foundation² describe habit reversal therapy, comprehensive behavioral treatment, and behavioral therapy that is enhanced by acceptance and commitment therapy or dialectical behavioral therapy (DBT) skills. (Although these guidelines also summarize possible pharmacologic interventions, medication for patients with BFRBs is not discussed in this article.)

Understanding the antecedents and consequences of these recurrent behaviors is a key aspect of psychotherapeutic treatments because diverse contingencies reinforce these repetitive behaviors. As with any comprehensive assessment, asking questions to understand the function of the behaviors guides personalized treatment recommendations or referrals. Mansueto et al³ described a systematic approach to assessing BFRBs. Asking questions based on these researchers’ SCAMP domains (Sensory, Cognitive, Affective, Motor, Place) can provide patients and clinicians with a clear picture of pulling, picking, or other repetitive behaviors.
 

Sensory. Start with an assessment of how sensory experiences might play into the cycle. Questions might include: Does the patient see a distinctive hair (eg, color, texture) or skin irregularity that draws them into the behavior? Do they visually inspect the hair or skin before, during, or after? Do they describe a premonitory sensation, such as an itch? Do they have a dermatologic condition that cues interoceptive hypervigilance? Do they taste or smell the scab, excoriate, or hair? Are they particularly attuned to the auditory experiences of the process (ie, hearing the pop or a pull)? Could any substances or medications be impacting the body’s restlessness?

Cognitive. Just as we assess common automatic thoughts associated with other psychopathologies, it is important to appreciate the cognitions that occur during this behavioral chain. Some thoughts involve an intolerance of imperfection: “That hair looks different. I have to remove it.” “It is important for pores to be completely clean.” Other thoughts may involve granting permission: “I’ll just pull one.” “It has been a long week so I deserve to do just this one.” Certainly, many patients may be thinking about other daily stressors, such as occupational or interpersonal difficulties. Knowing about the patient’s mental state throughout the BFRB can guide a clinician to recommend treatment focused on (for example) cognitive-behavioral therapy for perfectionism or approaches to address existing stressors. 

Affective. One common assumption is that patients who engage in BFRBs are anxious. While it certainly may be the case, an array of affective states may accompany the repetitive behavior. Patients may describe feeling tense, bored, sad, anxious, excited, relieved, agitated, guilty, worried, or ashamed. It is typically helpful to inquire about affect before, during, and after. Knowing the emotional experiences during and outside of BFRBs can call attention to possible comorbidities that warrant treatment, such as a mood or anxiety disorder. Additionally, dysregulation in affective states during the BFRB may point to useful adjunctive skills, such as DBT. 

Motor. Some patients describe being quite unaware of their BFRB (often called “automatic”), whereas for other patients pulling or picking may be directed and within awareness (often called “focused”). It is common for patients to have both automatic and focused behaviors. Questions to understand the motor experience include: Is the patient operating on autopilot when they are engaged in the behavior? Does the behavior occur more often in certain postures, such as when they are seated or lying in bed? Understanding the choreography of the BFRB can help in determining physical barriers to protect the skin or hair. 

Place. Finally, ask the patient if they believe certain locations increase the occurrence of the BFRB. For instance, some patients may notice the behavior is more likely to occur in the bathroom or bedroom. Bathrooms often contain implements associated with these behaviors, including mirrors, tweezers, or bright lights. Knowing where the BFRB is most likely to occur can help the clinician develop planning strategies to minimize behavioral engagement. An example is a patient who is more likely to pull or pick on a long commute from work. Planning to have a hat and sweater in their vehicle for the drive home may serve as a deterrent and break the cycle. When considering the place, it may also be helpful to ask about the time of day and presence of others.

Gathering information from the SCAMP domains can lead to individualized approaches to care. Of course, nonsuicidal self-injury, delusional parasitosis, or body dysmorphic disorder are a few of the many differential diagnoses that should be considered during the assessment. After a detailed assessment, clinicians can proceed by collaboratively developing strategies with the patient, referring them to a clinician who specializes in treating BFRBs using a resource such as the TLC Foundation’s Find a Therapist directory (https://www.bfrb.org/find-help-support/find-a-therapist), or recommending a self-guided resource such as StopPulling.com or StopPicking.com.

Repetitive behaviors towards the body, such as hair pulling and skin picking, are common. Approximately 5% of the general population may meet criteria for trichotillomania or excoriation disorder, in which the repetitive behaviors are excessive and impairing. The category of body-focused repetitive behaviors (BFRBs) extends beyond these 2 disorders to include onychophagia (nail biting), onychotillomania (nail picking), and lip or cheek chewing, which in DSM-5 are categorized under Other Specified Obsessive-Compulsive Disorder—BFRB. Of particular concern are trichophagia or dermatophagia, the ritualizing and eating of skin or hair that can lead to gastrointestinal complications.¹

The prevalence and associated distress from BFRBs have spurred increased research into psychotherapeutic interventions to remediate suffering and curb bodily damage. Under the broader umbrella of behavioral therapy or cognitive-behavioral therapy, the Expert Consensus Treatment Guidelines from the TLC Foundation² describe habit reversal therapy, comprehensive behavioral treatment, and behavioral therapy that is enhanced by acceptance and commitment therapy or dialectical behavioral therapy (DBT) skills. (Although these guidelines also summarize possible pharmacologic interventions, medication for patients with BFRBs is not discussed in this article.)

Understanding the antecedents and consequences of these recurrent behaviors is a key aspect of psychotherapeutic treatments because diverse contingencies reinforce these repetitive behaviors. As with any comprehensive assessment, asking questions to understand the function of the behaviors guides personalized treatment recommendations or referrals. Mansueto et al³ described a systematic approach to assessing BFRBs. Asking questions based on these researchers’ SCAMP domains (Sensory, Cognitive, Affective, Motor, Place) can provide patients and clinicians with a clear picture of pulling, picking, or other repetitive behaviors.
 

Sensory. Start with an assessment of how sensory experiences might play into the cycle. Questions might include: Does the patient see a distinctive hair (eg, color, texture) or skin irregularity that draws them into the behavior? Do they visually inspect the hair or skin before, during, or after? Do they describe a premonitory sensation, such as an itch? Do they have a dermatologic condition that cues interoceptive hypervigilance? Do they taste or smell the scab, excoriate, or hair? Are they particularly attuned to the auditory experiences of the process (ie, hearing the pop or a pull)? Could any substances or medications be impacting the body’s restlessness?

Cognitive. Just as we assess common automatic thoughts associated with other psychopathologies, it is important to appreciate the cognitions that occur during this behavioral chain. Some thoughts involve an intolerance of imperfection: “That hair looks different. I have to remove it.” “It is important for pores to be completely clean.” Other thoughts may involve granting permission: “I’ll just pull one.” “It has been a long week so I deserve to do just this one.” Certainly, many patients may be thinking about other daily stressors, such as occupational or interpersonal difficulties. Knowing about the patient’s mental state throughout the BFRB can guide a clinician to recommend treatment focused on (for example) cognitive-behavioral therapy for perfectionism or approaches to address existing stressors. 

Affective. One common assumption is that patients who engage in BFRBs are anxious. While it certainly may be the case, an array of affective states may accompany the repetitive behavior. Patients may describe feeling tense, bored, sad, anxious, excited, relieved, agitated, guilty, worried, or ashamed. It is typically helpful to inquire about affect before, during, and after. Knowing the emotional experiences during and outside of BFRBs can call attention to possible comorbidities that warrant treatment, such as a mood or anxiety disorder. Additionally, dysregulation in affective states during the BFRB may point to useful adjunctive skills, such as DBT. 

Motor. Some patients describe being quite unaware of their BFRB (often called “automatic”), whereas for other patients pulling or picking may be directed and within awareness (often called “focused”). It is common for patients to have both automatic and focused behaviors. Questions to understand the motor experience include: Is the patient operating on autopilot when they are engaged in the behavior? Does the behavior occur more often in certain postures, such as when they are seated or lying in bed? Understanding the choreography of the BFRB can help in determining physical barriers to protect the skin or hair. 

Place. Finally, ask the patient if they believe certain locations increase the occurrence of the BFRB. For instance, some patients may notice the behavior is more likely to occur in the bathroom or bedroom. Bathrooms often contain implements associated with these behaviors, including mirrors, tweezers, or bright lights. Knowing where the BFRB is most likely to occur can help the clinician develop planning strategies to minimize behavioral engagement. An example is a patient who is more likely to pull or pick on a long commute from work. Planning to have a hat and sweater in their vehicle for the drive home may serve as a deterrent and break the cycle. When considering the place, it may also be helpful to ask about the time of day and presence of others.

Gathering information from the SCAMP domains can lead to individualized approaches to care. Of course, nonsuicidal self-injury, delusional parasitosis, or body dysmorphic disorder are a few of the many differential diagnoses that should be considered during the assessment. After a detailed assessment, clinicians can proceed by collaboratively developing strategies with the patient, referring them to a clinician who specializes in treating BFRBs using a resource such as the TLC Foundation’s Find a Therapist directory (https://www.bfrb.org/find-help-support/find-a-therapist), or recommending a self-guided resource such as StopPulling.com or StopPicking.com.

Spesolimab, a humanized, anti–interleukin-36 receptor monoclonal antibody, was associated with rapid improvement in pustules during flares, in a phase 2 study of 53 adults with generalized pustular psoriasis (GPP).

GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.

“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.

In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.

The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.

After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).

Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).

In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.

“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.

“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.

The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.

The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.

No FDA-approved therapy

“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”

Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added. 

Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”

On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.

The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.

Spesolimab, a humanized, anti–interleukin-36 receptor monoclonal antibody, was associated with rapid improvement in pustules during flares, in a phase 2 study of 53 adults with generalized pustular psoriasis (GPP).

GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.

“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.

In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.

The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.

After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).

Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).

In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.

“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.

“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.

The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.

The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.

No FDA-approved therapy

“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”

Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added. 

Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”

On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.

The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.

Spesolimab, a humanized, anti–interleukin-36 receptor monoclonal antibody, was associated with rapid improvement in pustules during flares, in a phase 2 study of 53 adults with generalized pustular psoriasis (GPP).

GPP is a life-threatening skin condition involving the widespread eruption of sterile pustules, with a clinical course that “can be relapsing with recurrent flares or persistent with intermittent flares,” Hervé Bachelez, MD, of the Université de Paris and coauthors wrote. GPP patients are often hospitalized, and mortality ranges from 2% to 16% from causes that include sepsis and cardiorespiratory failure.

“The role of the interleukin-36 pathway in GPP is supported by the finding of loss-of-function mutations in the interleukin-36 receptor antagonist gene (IL36RN) and associated genes (CARD14, AP1S3, SERPINA3, and MPO) and by the overexpression of interleukin-36 cytokines in GPP skin lesions,” therefore, IL-36 is a potential treatment target to manage flares, they explained.

In the multicenter, double-blind trial, published in the New England Journal of Medicine, the researchers randomized 35 adults with GPP flares to a single 900-mg intravenous dose of spesolimab and 18 to placebo. Patients in both groups could receive an open-label dose of spesolimab after day 8; all patients were followed for 12 weeks.

The primary study endpoint was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at 1 week after treatment. The GPPGA ranges from 0 (no visible pustules) to 4 (severe pustules). At baseline, 46% spesolimab patients and 39% placebo patients had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.

After 1 week, 54% of the spesolimab patients had no visible pustules, compared with 6% of placebo patients; the difference was statistically significant (P < .001). The main secondary endpoint was a score of 0 or 1 (clear or almost clear skin) on the GPPGA total score after 1 week. Significantly more spesolimab patients had GPPGA total scores of 0 or 1, compared with placebo patients (43% vs. 11%, respectively; P = .02).

Overall, 6 of 35 spesolimab patients (17%) and 6% of those in the placebo groups developed infections during the first week, and 24 of 51 patients (47%) who had received spesolimab at any point during the study developed infections by week 12. Infections included urinary tract infections (three cases), influenza (three), otitis externa (two), folliculitis (two), upper respiratory tract infection (two), and pustule (two).

In the first week, 6% of spesolimab patients and none of the placebo patients reported serious adverse events; at week 12, 12% of patients who had received at least one spesolimab dose reported a serious adverse event. In addition, antidrug antibodies were identified in 23 (46%) of the 50 patients who received at least one dose of spesolimab.

“Symptoms that were observed in two patients who received spesolimab were reported as a drug reaction with eosinophilia and systemic symptoms (DRESS),” the authors noted. One patient had a RegiSCAR (European Registry of Severe Cutaneous Adverse Reactions) score and the other had a score of 3; a score below 2 indicates no DRESS, and a score of 2 or 3 indicates “possible DRESS,” they added.

“Because 15 of the 18 patients who were assigned to the placebo group received open-label spesolimab, the effect of spesolimab as compared with that of placebo could not be determined after week 1,” the researchers noted.

The study findings were limited by several factors including the short randomization period and small study population, the researchers noted. However, the effect sizes for both the primary and secondary endpoints were large, which strengthened the results.

The results support data from previous studies suggesting a role for IL-36 in the pathogenesis of GPP, and support the need for longer and larger studies of the safety and effectiveness of spesolimab for GPP patients, they concluded.

No FDA-approved therapy

“GPP is a very rare but devastating life-threatening disease that presents with the sudden onset of pustules throughout the skin,” Joel Gelfand, MD, professor of dermatology and director of the psoriasis and phototherapy center at the University of Pennsylvania, Philadelphia, said in an interview. “Without rapid treatment, GPP can result in death. Currently there are no [Food and Drug Administration]–approved treatments for this orphan disease.”

Dr. Gelfand said he was surprised by the degree of efficacy and the speed of the patient response to spesolimab, compared with placebo, which he described as “truly remarkable.” Based on the current study results, “spesolimab offers a tremendous step forward for our patients,” he added. 

Looking ahead, Dr. Gelfand noted that “longer-term studies with a comparator, such as a biologic that targets IL-17, would be helpful to more fully understand the safety, efficacy, and role that spesolimab will have in real-world patients.”

On Dec. 15, Boehringer Ingelheim announced that the FDA had granted priority review for spesolimab for treating GPP flares.

The study was supported by Boehringer Ingelheim. Lead author Dr. Bachelez had no financial conflicts to disclose. Several authors are employees of Boehringer Ingelheim. Dr. Gelfand is a consultant for the study sponsor Boehringer Ingelheim and has received research grants from Boehringer Ingelheim to his institution to support an investigator-initiated study. He also disclosed serving as a consultant and receiving research grants from other manufacturers of psoriasis products.

Many patients with nonmetastatic prostate cancer are asymptomatic at the time of diagnosis due to widespread routine screening. When localized symptoms do occur, they may include urinary frequency, decreased urine stream, urinary urgency, and hematuria. An increasing proportion of patients with localized disease are asymptomatic, however; such signs and symptoms may well be related to age-associated prostate enlargement or other conditions. Nevertheless, men over the age of 50 years who present with urinary symptoms should be screened for prostate cancer using DRE and PSA. Benign prostatic hyperplasia, for example, can manifest in urinary symptoms and even elevate PSA. Acute prostatitis, on the other hand, presents as a urinary tract infection.

Because this patient showed elevated PSA levels, albeit with normal DRE findings, needle biopsy of the prostate is indicated for tissue diagnosis, usually performed with transrectal ultrasound. A pathologic evaluation of the biopsy specimen will determine the patient's Gleason score. PSA density (amount of PSA per gram of prostate tissue) and PSA doubling time should be collected as well. As seen in the present case, MRI can be used to assess lesions concerning for prostate cancer prior to biopsy. Lesions are then assigned Prostate Imaging–Reporting and Data System (PI-RADS) scores depending on their location within the prostatic zones. Imaging is also useful in staging and active surveillance. Staging is based on the tumor, node, and metastasis (TNM), with clinically localized prostate cancers including any T, N0, M0, NX, or MX cases. The clinician should pursue genetic testing to determine the presence of high-risk germline mutations. 

The NCCN Guidelines recommend that for clinically localized prostate cancer, approaches include watchful waiting, active surveillance, radical prostatectomy, and radiation therapy. For asymptomatic patients who are older and/or have other serious comorbidities, active surveillance is often suggested. Radical prostatectomy is typically reserved for patients with a life expectancy of 10 years or more. Pelvic lymph node dissection may be performed on the basis of probability of nodal metastasis. Radiotherapy is also potentially curative in localized prostate cancer and may be delivered via brachytherapy, proton radiation, or external beam radiation therapy (EBRT). EBRT techniques include intensity-modulated radiation therapy (IMRT) and hypofractionated, image-guided stereotactic body radiation therapy (SBRT).

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Cvico Medical Solutions

Many patients with nonmetastatic prostate cancer are asymptomatic at the time of diagnosis due to widespread routine screening. When localized symptoms do occur, they may include urinary frequency, decreased urine stream, urinary urgency, and hematuria. An increasing proportion of patients with localized disease are asymptomatic, however; such signs and symptoms may well be related to age-associated prostate enlargement or other conditions. Nevertheless, men over the age of 50 years who present with urinary symptoms should be screened for prostate cancer using DRE and PSA. Benign prostatic hyperplasia, for example, can manifest in urinary symptoms and even elevate PSA. Acute prostatitis, on the other hand, presents as a urinary tract infection.

Because this patient showed elevated PSA levels, albeit with normal DRE findings, needle biopsy of the prostate is indicated for tissue diagnosis, usually performed with transrectal ultrasound. A pathologic evaluation of the biopsy specimen will determine the patient's Gleason score. PSA density (amount of PSA per gram of prostate tissue) and PSA doubling time should be collected as well. As seen in the present case, MRI can be used to assess lesions concerning for prostate cancer prior to biopsy. Lesions are then assigned Prostate Imaging–Reporting and Data System (PI-RADS) scores depending on their location within the prostatic zones. Imaging is also useful in staging and active surveillance. Staging is based on the tumor, node, and metastasis (TNM), with clinically localized prostate cancers including any T, N0, M0, NX, or MX cases. The clinician should pursue genetic testing to determine the presence of high-risk germline mutations. 

The NCCN Guidelines recommend that for clinically localized prostate cancer, approaches include watchful waiting, active surveillance, radical prostatectomy, and radiation therapy. For asymptomatic patients who are older and/or have other serious comorbidities, active surveillance is often suggested. Radical prostatectomy is typically reserved for patients with a life expectancy of 10 years or more. Pelvic lymph node dissection may be performed on the basis of probability of nodal metastasis. Radiotherapy is also potentially curative in localized prostate cancer and may be delivered via brachytherapy, proton radiation, or external beam radiation therapy (EBRT). EBRT techniques include intensity-modulated radiation therapy (IMRT) and hypofractionated, image-guided stereotactic body radiation therapy (SBRT).

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Cvico Medical Solutions

Many patients with nonmetastatic prostate cancer are asymptomatic at the time of diagnosis due to widespread routine screening. When localized symptoms do occur, they may include urinary frequency, decreased urine stream, urinary urgency, and hematuria. An increasing proportion of patients with localized disease are asymptomatic, however; such signs and symptoms may well be related to age-associated prostate enlargement or other conditions. Nevertheless, men over the age of 50 years who present with urinary symptoms should be screened for prostate cancer using DRE and PSA. Benign prostatic hyperplasia, for example, can manifest in urinary symptoms and even elevate PSA. Acute prostatitis, on the other hand, presents as a urinary tract infection.

Because this patient showed elevated PSA levels, albeit with normal DRE findings, needle biopsy of the prostate is indicated for tissue diagnosis, usually performed with transrectal ultrasound. A pathologic evaluation of the biopsy specimen will determine the patient's Gleason score. PSA density (amount of PSA per gram of prostate tissue) and PSA doubling time should be collected as well. As seen in the present case, MRI can be used to assess lesions concerning for prostate cancer prior to biopsy. Lesions are then assigned Prostate Imaging–Reporting and Data System (PI-RADS) scores depending on their location within the prostatic zones. Imaging is also useful in staging and active surveillance. Staging is based on the tumor, node, and metastasis (TNM), with clinically localized prostate cancers including any T, N0, M0, NX, or MX cases. The clinician should pursue genetic testing to determine the presence of high-risk germline mutations. 

The NCCN Guidelines recommend that for clinically localized prostate cancer, approaches include watchful waiting, active surveillance, radical prostatectomy, and radiation therapy. For asymptomatic patients who are older and/or have other serious comorbidities, active surveillance is often suggested. Radical prostatectomy is typically reserved for patients with a life expectancy of 10 years or more. Pelvic lymph node dissection may be performed on the basis of probability of nodal metastasis. Radiotherapy is also potentially curative in localized prostate cancer and may be delivered via brachytherapy, proton radiation, or external beam radiation therapy (EBRT). EBRT techniques include intensity-modulated radiation therapy (IMRT) and hypofractionated, image-guided stereotactic body radiation therapy (SBRT).

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Cvico Medical Solutions

I had seen many new and exciting presentations of psychopathology during my intern year, yet one patient was uniquely memorable. When stable, he worked as a counselor, though for any number of reasons (eg, missing a dose of medication, smoking marijuana) his manic symptoms would emerge quickly, the disease rearing its ugly head within hours. He would become extremely hyperactive, elated, disinhibited (running naked in the streets), and grandiose (believing he was working for the president). He would be escorted to our psychiatric emergency department (ED) by police, who would have to resort to handcuffing him. His symptoms were described by ED and inpatient nursing staff and residents as “disorganized,” “psychotic,” “agitated,”’ or “combative.” He would receive large doses of intramuscular (IM) haloperidol, chlorpromazine, and diphenhydramine in desperate attempts to rein in his mania. Frustratingly—and paradoxically— this would make him more confused, disoriented, restless, and hyperactive, and often led to the need for restraints.

This behavior persisted for days until an attending I was working with assessed him. The attending observed that the patient did not know his current location, day of the week or month, or how he ended up in the hospital. He observed this patient intermittently staring, making abnormal repetitive movements with his arms and hands, occasionally freezing, making impulsive movements, and becoming combative without provocation. His heart rate and temperature were elevated; he was diaphoretic, especially after receiving parenteral antipsychotics. The attending, a pupil of Max Fink, made the diagnosis: delirious mania, a form of catatonia.^1,2 Resolution was quick and complete after 6 bilateral electroconvulsive therapy (ECT) sessions.

Catatonia, a neuropsychiatric phenomenon characterized by abnormal speech, movement, and affect, has undergone numerous paradigm shifts since it was recognized by Karl Ludwig Kahlbaum in 1874.³ Shortly after Kahlbaum, Emil Kraepelin held the belief that catatonia was a subtype of dementia praecox, or what is now known as schizophrenia.⁴ Due to this, patients were likely receiving less-than-optimal treatments, because their catatonia was being diagnosed as acute psychosis. Finally, in DSM-5, catatonia was unshackled from the constraints of schizophrenia and is now an entity of its own.⁵ However, catatonia is often met with incertitude (despite being present in up to 15% of inpatients),¹ with its treatment typically delayed or not even pursued. This is amplified because many forms of catatonia are often misdiagnosed as disorders that are more common or better understood.

Potential catatonia presentations

Delirious mania. Patients with delirious mania typically present with acute delirium, severe paranoia, hyperactivity, and visual/auditory hallucinations.^2,6,7 They usually have excited catatonic signs, such as excessive movement, combativeness, impulsivity, stereotypy, and echophenomena. Unfortunately, the catatonia is overshadowed by extreme psychotic and manic symptoms, or delirium (for which an underlying medical cause is usually not found). As was the case for the patient I described earlier, large doses of IM antipsychotics usually are administered, which can cause neuroleptic malignant syndrome (NMS) or precipitate seizures.⁸

Neuroleptic malignant syndrome. NMS is marked by fever, elevated blood pressure and heart rate, lead-pipe rigidity, parkinsonian features, altered mental status, and lab abnormalities (elevated liver enzymes or creatinine phosphokinase). This syndrome is preceded by the administration of an antipsychotic. It has features of catatonia that include mutism, negativism, and posturing.⁹ NMS is commonly interpreted as a subtype of malignant catatonia. Some argue that the diagnosis of malignant catatonia yields a more favorable outcome because it leads to more effective treatments (ie, benzodiazepines and ECT as opposed to dopamine agonists and dantrolene).¹⁰ Because NMS has much overlap with serotonin syndrome and drug-induced parkinsonism, initiation of benzodiazepines and ECT often is delayed.¹¹

Retarded catatonia. This version of catatonia usually is well recognized. The typical presentation is a patient who does not speak (mutism) or move (stupor), stares, becomes withdrawn (does not eat or drink), or maintains abnormal posturing. Retarded catatonia can be confused with a major depressive episode or hypoactive delirium.

Catatonia in autism spectrum disorder. Historically, co-occurring catatonia and autism spectrum disorder (ASD) was believed to be extremely rare. However, recent retrospective studies have found that up to 17% of patients with ASD older than age 15 have catatonia.¹² Many pediatric psychiatrists fail to recognize catatonia; in 1 study, only 2 patients (of 18) were correctly identified as having catatonia.¹³ The catatonic signs may vary, but the core features include withdrawal (children may need a feeding tube), decreased communication and/or worsening psychomotor slowing, agitation, or stereotypical movements, which can manifest as worsening self-injurious behavior.^14,15

An approach to treatment

Regardless of the etiology or presentation, first-line treatment for catatonia is benzodiazepines and/or ECT. A lorazepam challenge is used for diagnostic clarification; if effective, lorazepam can be titrated until symptoms fully resolve.^16,17 Doses >20 mg have been reported as effective and well-tolerated, without the feared sedation and respiratory depression.⁶ An unsuccessful lorazepam challenge does not rule out catatonia. If benzodiazepine therapy fails or the patient requires immediate symptom relief, ECT is the most effective treatment. Many clinicians use a bilateral electrode placement with high-energy dosing and frequent sessions until the catatonia resolves.^1,18

In my experience, catatonia in all its forms remains poorly recognized, with its treatment questioned. Residents—especially those in psychiatry—must understand that catatonia can result in systemic illness or death.

I had seen many new and exciting presentations of psychopathology during my intern year, yet one patient was uniquely memorable. When stable, he worked as a counselor, though for any number of reasons (eg, missing a dose of medication, smoking marijuana) his manic symptoms would emerge quickly, the disease rearing its ugly head within hours. He would become extremely hyperactive, elated, disinhibited (running naked in the streets), and grandiose (believing he was working for the president). He would be escorted to our psychiatric emergency department (ED) by police, who would have to resort to handcuffing him. His symptoms were described by ED and inpatient nursing staff and residents as “disorganized,” “psychotic,” “agitated,”’ or “combative.” He would receive large doses of intramuscular (IM) haloperidol, chlorpromazine, and diphenhydramine in desperate attempts to rein in his mania. Frustratingly—and paradoxically— this would make him more confused, disoriented, restless, and hyperactive, and often led to the need for restraints.

This behavior persisted for days until an attending I was working with assessed him. The attending observed that the patient did not know his current location, day of the week or month, or how he ended up in the hospital. He observed this patient intermittently staring, making abnormal repetitive movements with his arms and hands, occasionally freezing, making impulsive movements, and becoming combative without provocation. His heart rate and temperature were elevated; he was diaphoretic, especially after receiving parenteral antipsychotics. The attending, a pupil of Max Fink, made the diagnosis: delirious mania, a form of catatonia.^1,2 Resolution was quick and complete after 6 bilateral electroconvulsive therapy (ECT) sessions.

Catatonia, a neuropsychiatric phenomenon characterized by abnormal speech, movement, and affect, has undergone numerous paradigm shifts since it was recognized by Karl Ludwig Kahlbaum in 1874.³ Shortly after Kahlbaum, Emil Kraepelin held the belief that catatonia was a subtype of dementia praecox, or what is now known as schizophrenia.⁴ Due to this, patients were likely receiving less-than-optimal treatments, because their catatonia was being diagnosed as acute psychosis. Finally, in DSM-5, catatonia was unshackled from the constraints of schizophrenia and is now an entity of its own.⁵ However, catatonia is often met with incertitude (despite being present in up to 15% of inpatients),¹ with its treatment typically delayed or not even pursued. This is amplified because many forms of catatonia are often misdiagnosed as disorders that are more common or better understood.

Potential catatonia presentations

Delirious mania. Patients with delirious mania typically present with acute delirium, severe paranoia, hyperactivity, and visual/auditory hallucinations.^2,6,7 They usually have excited catatonic signs, such as excessive movement, combativeness, impulsivity, stereotypy, and echophenomena. Unfortunately, the catatonia is overshadowed by extreme psychotic and manic symptoms, or delirium (for which an underlying medical cause is usually not found). As was the case for the patient I described earlier, large doses of IM antipsychotics usually are administered, which can cause neuroleptic malignant syndrome (NMS) or precipitate seizures.⁸

Neuroleptic malignant syndrome. NMS is marked by fever, elevated blood pressure and heart rate, lead-pipe rigidity, parkinsonian features, altered mental status, and lab abnormalities (elevated liver enzymes or creatinine phosphokinase). This syndrome is preceded by the administration of an antipsychotic. It has features of catatonia that include mutism, negativism, and posturing.⁹ NMS is commonly interpreted as a subtype of malignant catatonia. Some argue that the diagnosis of malignant catatonia yields a more favorable outcome because it leads to more effective treatments (ie, benzodiazepines and ECT as opposed to dopamine agonists and dantrolene).¹⁰ Because NMS has much overlap with serotonin syndrome and drug-induced parkinsonism, initiation of benzodiazepines and ECT often is delayed.¹¹

Retarded catatonia. This version of catatonia usually is well recognized. The typical presentation is a patient who does not speak (mutism) or move (stupor), stares, becomes withdrawn (does not eat or drink), or maintains abnormal posturing. Retarded catatonia can be confused with a major depressive episode or hypoactive delirium.

Catatonia in autism spectrum disorder. Historically, co-occurring catatonia and autism spectrum disorder (ASD) was believed to be extremely rare. However, recent retrospective studies have found that up to 17% of patients with ASD older than age 15 have catatonia.¹² Many pediatric psychiatrists fail to recognize catatonia; in 1 study, only 2 patients (of 18) were correctly identified as having catatonia.¹³ The catatonic signs may vary, but the core features include withdrawal (children may need a feeding tube), decreased communication and/or worsening psychomotor slowing, agitation, or stereotypical movements, which can manifest as worsening self-injurious behavior.^14,15

An approach to treatment

Regardless of the etiology or presentation, first-line treatment for catatonia is benzodiazepines and/or ECT. A lorazepam challenge is used for diagnostic clarification; if effective, lorazepam can be titrated until symptoms fully resolve.^16,17 Doses >20 mg have been reported as effective and well-tolerated, without the feared sedation and respiratory depression.⁶ An unsuccessful lorazepam challenge does not rule out catatonia. If benzodiazepine therapy fails or the patient requires immediate symptom relief, ECT is the most effective treatment. Many clinicians use a bilateral electrode placement with high-energy dosing and frequent sessions until the catatonia resolves.^1,18

In my experience, catatonia in all its forms remains poorly recognized, with its treatment questioned. Residents—especially those in psychiatry—must understand that catatonia can result in systemic illness or death.

I had seen many new and exciting presentations of psychopathology during my intern year, yet one patient was uniquely memorable. When stable, he worked as a counselor, though for any number of reasons (eg, missing a dose of medication, smoking marijuana) his manic symptoms would emerge quickly, the disease rearing its ugly head within hours. He would become extremely hyperactive, elated, disinhibited (running naked in the streets), and grandiose (believing he was working for the president). He would be escorted to our psychiatric emergency department (ED) by police, who would have to resort to handcuffing him. His symptoms were described by ED and inpatient nursing staff and residents as “disorganized,” “psychotic,” “agitated,”’ or “combative.” He would receive large doses of intramuscular (IM) haloperidol, chlorpromazine, and diphenhydramine in desperate attempts to rein in his mania. Frustratingly—and paradoxically— this would make him more confused, disoriented, restless, and hyperactive, and often led to the need for restraints.

This behavior persisted for days until an attending I was working with assessed him. The attending observed that the patient did not know his current location, day of the week or month, or how he ended up in the hospital. He observed this patient intermittently staring, making abnormal repetitive movements with his arms and hands, occasionally freezing, making impulsive movements, and becoming combative without provocation. His heart rate and temperature were elevated; he was diaphoretic, especially after receiving parenteral antipsychotics. The attending, a pupil of Max Fink, made the diagnosis: delirious mania, a form of catatonia.^1,2 Resolution was quick and complete after 6 bilateral electroconvulsive therapy (ECT) sessions.

Catatonia, a neuropsychiatric phenomenon characterized by abnormal speech, movement, and affect, has undergone numerous paradigm shifts since it was recognized by Karl Ludwig Kahlbaum in 1874.³ Shortly after Kahlbaum, Emil Kraepelin held the belief that catatonia was a subtype of dementia praecox, or what is now known as schizophrenia.⁴ Due to this, patients were likely receiving less-than-optimal treatments, because their catatonia was being diagnosed as acute psychosis. Finally, in DSM-5, catatonia was unshackled from the constraints of schizophrenia and is now an entity of its own.⁵ However, catatonia is often met with incertitude (despite being present in up to 15% of inpatients),¹ with its treatment typically delayed or not even pursued. This is amplified because many forms of catatonia are often misdiagnosed as disorders that are more common or better understood.

Potential catatonia presentations

Delirious mania. Patients with delirious mania typically present with acute delirium, severe paranoia, hyperactivity, and visual/auditory hallucinations.^2,6,7 They usually have excited catatonic signs, such as excessive movement, combativeness, impulsivity, stereotypy, and echophenomena. Unfortunately, the catatonia is overshadowed by extreme psychotic and manic symptoms, or delirium (for which an underlying medical cause is usually not found). As was the case for the patient I described earlier, large doses of IM antipsychotics usually are administered, which can cause neuroleptic malignant syndrome (NMS) or precipitate seizures.⁸

Neuroleptic malignant syndrome. NMS is marked by fever, elevated blood pressure and heart rate, lead-pipe rigidity, parkinsonian features, altered mental status, and lab abnormalities (elevated liver enzymes or creatinine phosphokinase). This syndrome is preceded by the administration of an antipsychotic. It has features of catatonia that include mutism, negativism, and posturing.⁹ NMS is commonly interpreted as a subtype of malignant catatonia. Some argue that the diagnosis of malignant catatonia yields a more favorable outcome because it leads to more effective treatments (ie, benzodiazepines and ECT as opposed to dopamine agonists and dantrolene).¹⁰ Because NMS has much overlap with serotonin syndrome and drug-induced parkinsonism, initiation of benzodiazepines and ECT often is delayed.¹¹

Retarded catatonia. This version of catatonia usually is well recognized. The typical presentation is a patient who does not speak (mutism) or move (stupor), stares, becomes withdrawn (does not eat or drink), or maintains abnormal posturing. Retarded catatonia can be confused with a major depressive episode or hypoactive delirium.

Catatonia in autism spectrum disorder. Historically, co-occurring catatonia and autism spectrum disorder (ASD) was believed to be extremely rare. However, recent retrospective studies have found that up to 17% of patients with ASD older than age 15 have catatonia.¹² Many pediatric psychiatrists fail to recognize catatonia; in 1 study, only 2 patients (of 18) were correctly identified as having catatonia.¹³ The catatonic signs may vary, but the core features include withdrawal (children may need a feeding tube), decreased communication and/or worsening psychomotor slowing, agitation, or stereotypical movements, which can manifest as worsening self-injurious behavior.^14,15

An approach to treatment

Regardless of the etiology or presentation, first-line treatment for catatonia is benzodiazepines and/or ECT. A lorazepam challenge is used for diagnostic clarification; if effective, lorazepam can be titrated until symptoms fully resolve.^16,17 Doses >20 mg have been reported as effective and well-tolerated, without the feared sedation and respiratory depression.⁶ An unsuccessful lorazepam challenge does not rule out catatonia. If benzodiazepine therapy fails or the patient requires immediate symptom relief, ECT is the most effective treatment. Many clinicians use a bilateral electrode placement with high-energy dosing and frequent sessions until the catatonia resolves.^1,18

In my experience, catatonia in all its forms remains poorly recognized, with its treatment questioned. Residents—especially those in psychiatry—must understand that catatonia can result in systemic illness or death.

Ulcerative colitis (UC) is an autoimmune-related inflammatory bowel disease (IBD). It typically develops in the rectum and extends to involve the large intestine. Pediatric UC can have a more severe phenotype than adult disease and may affect a child's pubertal development, bone mineral density, nutrition levels, and social life. It is currently theorized that the age at diagnosis and sex of the patient do not predict disease activity.

UC disease can announce itself as mild, moderate, or severe, and the Pediatric Ulcerative Colitis Activity Index (PUCAI) endoscopic grading is used as a clinical scoring system. The most common presenting symptoms are rectal bleeding, diarrhea, and abdominal pain; among children, the presentation can vary.

Crohns disease, another IBD, must be carefully ruled out of the differential. Colonoscopy represents the first-line approach in the diagnosis of IBD. The findings that would suggest Crohns disease are sparing of the rectal mucosa, aphthous ulceration, and noncontiguous (or skip) lesions. Micronutrient and vitamin levels are usually low in Crohns disease. And although weight loss, perineal disease, fistulae, and obstruction are commonly seen in the context of Crohns disease, they are uncommon or rare in UC. Bleeding is observed much more frequently in UC. 

During UC workup, elevated erythrocyte sedimentation rate and C-reactive protein level often serve as markers of disease activity. Antineutrophil cytoplasmic antibody (ANCA) test is frequently used with suspected UC (though this measure may not correlate with disease activity). In addition, a broad metabolic panel should be performed, along with stool cultures, to rule out infection.

The goals of pediatric UC management are to maintain control of the disease, extend periods of remission, and reduce long-term damage caused by inflammation, all while potentially allowing the patient to function as normally as possible. Anti-inflammatory therapy with 5-aminosalicylic acid agents, such as sulfasalazine and mesalamine, is foundational to treatment. Acute flares of UC in the pediatric population are usually responsive to corticosteroids, but these regimens should be short-term only. Immunomodulatory agents, tumor necrosis factor inhibitors, and newer therapies such as monoclonal antibodies are also used during flares, but only a minority of patients will require these therapies. These are also considered treatment alternatives for patients who are steroid-dependent or steroid-refractory.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

Ulcerative colitis (UC) is an autoimmune-related inflammatory bowel disease (IBD). It typically develops in the rectum and extends to involve the large intestine. Pediatric UC can have a more severe phenotype than adult disease and may affect a child's pubertal development, bone mineral density, nutrition levels, and social life. It is currently theorized that the age at diagnosis and sex of the patient do not predict disease activity.

UC disease can announce itself as mild, moderate, or severe, and the Pediatric Ulcerative Colitis Activity Index (PUCAI) endoscopic grading is used as a clinical scoring system. The most common presenting symptoms are rectal bleeding, diarrhea, and abdominal pain; among children, the presentation can vary.

Crohns disease, another IBD, must be carefully ruled out of the differential. Colonoscopy represents the first-line approach in the diagnosis of IBD. The findings that would suggest Crohns disease are sparing of the rectal mucosa, aphthous ulceration, and noncontiguous (or skip) lesions. Micronutrient and vitamin levels are usually low in Crohns disease. And although weight loss, perineal disease, fistulae, and obstruction are commonly seen in the context of Crohns disease, they are uncommon or rare in UC. Bleeding is observed much more frequently in UC. 

During UC workup, elevated erythrocyte sedimentation rate and C-reactive protein level often serve as markers of disease activity. Antineutrophil cytoplasmic antibody (ANCA) test is frequently used with suspected UC (though this measure may not correlate with disease activity). In addition, a broad metabolic panel should be performed, along with stool cultures, to rule out infection.

The goals of pediatric UC management are to maintain control of the disease, extend periods of remission, and reduce long-term damage caused by inflammation, all while potentially allowing the patient to function as normally as possible. Anti-inflammatory therapy with 5-aminosalicylic acid agents, such as sulfasalazine and mesalamine, is foundational to treatment. Acute flares of UC in the pediatric population are usually responsive to corticosteroids, but these regimens should be short-term only. Immunomodulatory agents, tumor necrosis factor inhibitors, and newer therapies such as monoclonal antibodies are also used during flares, but only a minority of patients will require these therapies. These are also considered treatment alternatives for patients who are steroid-dependent or steroid-refractory.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

Ulcerative colitis (UC) is an autoimmune-related inflammatory bowel disease (IBD). It typically develops in the rectum and extends to involve the large intestine. Pediatric UC can have a more severe phenotype than adult disease and may affect a child's pubertal development, bone mineral density, nutrition levels, and social life. It is currently theorized that the age at diagnosis and sex of the patient do not predict disease activity.

UC disease can announce itself as mild, moderate, or severe, and the Pediatric Ulcerative Colitis Activity Index (PUCAI) endoscopic grading is used as a clinical scoring system. The most common presenting symptoms are rectal bleeding, diarrhea, and abdominal pain; among children, the presentation can vary.

Crohns disease, another IBD, must be carefully ruled out of the differential. Colonoscopy represents the first-line approach in the diagnosis of IBD. The findings that would suggest Crohns disease are sparing of the rectal mucosa, aphthous ulceration, and noncontiguous (or skip) lesions. Micronutrient and vitamin levels are usually low in Crohns disease. And although weight loss, perineal disease, fistulae, and obstruction are commonly seen in the context of Crohns disease, they are uncommon or rare in UC. Bleeding is observed much more frequently in UC. 

During UC workup, elevated erythrocyte sedimentation rate and C-reactive protein level often serve as markers of disease activity. Antineutrophil cytoplasmic antibody (ANCA) test is frequently used with suspected UC (though this measure may not correlate with disease activity). In addition, a broad metabolic panel should be performed, along with stool cultures, to rule out infection.

The goals of pediatric UC management are to maintain control of the disease, extend periods of remission, and reduce long-term damage caused by inflammation, all while potentially allowing the patient to function as normally as possible. Anti-inflammatory therapy with 5-aminosalicylic acid agents, such as sulfasalazine and mesalamine, is foundational to treatment. Acute flares of UC in the pediatric population are usually responsive to corticosteroids, but these regimens should be short-term only. Immunomodulatory agents, tumor necrosis factor inhibitors, and newer therapies such as monoclonal antibodies are also used during flares, but only a minority of patients will require these therapies. These are also considered treatment alternatives for patients who are steroid-dependent or steroid-refractory.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

All of the above conditions can have ophthalmic manifestations, but the majority of optic neuritis cases seen in clinical practice are either sporadic or MS related. Optic neuritis is the first demyelinating event in approximately 20% of patients with MS. It develops in approximately 40% of MS patients during the course of their disease. 

Optic neuritis is characterized by loss of vision (or loss of color vision) in the affected eye and pain on movement of the eye (painful ophthalmoplegia). Less often, patients with optic neuritis may describe phosphenes (transient flashes of light or black squares) lasting from hours to months. Phosphenes may occur before or during an optic neuritis event or even several months after recovery.

The diagnosis of optic neuritis is usually made clinically, with direct imaging of the optic nerves showing evidence of optic disc swelling with blurred margins. The real contribution of imaging in the setting of optic neuritis, however, is made by imaging of the brain, not of the optic nerves themselves. MRI of the brain provides information that can change the management of optic neuritis and yields prognostic information regarding the patient's future risk of developing MS. The most valuable predictor of the development of subsequent MS is the presence of white matter abnormalities. Between 27% and 70% of patients (in various studies) with isolated optic neuritis showed abnormal MRI brain findings, as defined by the presence of two or more white matter lesions on T2-weighted images. Patients with two or more lesions may have up to an 80% chance of meeting criteria for MS within the next 5 years. 

A gradual recovery of visual acuity with time is characteristic of optic neuritis, although permanent residual deficits in color vision and contrast and brightness sensitivity are common. The symptoms of optic neuritis will usually resolve without medical treatment, although continuing to take regular MS disease-modulating medication is usually helpful. An intravenous steroid or oral prednisone is sometimes recommended to speed recovery. A 3- to 5-day course of high-dose (1 g) IV methylprednisolone, followed by a rapid oral taper of prednisone, has been shown to provide rapid recovery of symptoms in the acute phase. However, IV steroids do little to affect the ultimate visual acuity in patients with optic neuritis.

Typically, patients begin to recover 2-4 weeks after the onset of the vision loss. The optic nerve may take up to 6-12 months to heal completely, but most patients recover as much vision as they are going to within the first few months.

For patients with optic neuritis whose brain lesions on MRI indicate a high risk of developing clinically definite MS, treatment with immunomodulators may be considered. IV immunoglobulin treatment of acute optic neuritis has been shown to have no beneficial effect. In severe cases, plasma exchange may be considered.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ.

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme.

All of the above conditions can have ophthalmic manifestations, but the majority of optic neuritis cases seen in clinical practice are either sporadic or MS related. Optic neuritis is the first demyelinating event in approximately 20% of patients with MS. It develops in approximately 40% of MS patients during the course of their disease. 

Optic neuritis is characterized by loss of vision (or loss of color vision) in the affected eye and pain on movement of the eye (painful ophthalmoplegia). Less often, patients with optic neuritis may describe phosphenes (transient flashes of light or black squares) lasting from hours to months. Phosphenes may occur before or during an optic neuritis event or even several months after recovery.

The diagnosis of optic neuritis is usually made clinically, with direct imaging of the optic nerves showing evidence of optic disc swelling with blurred margins. The real contribution of imaging in the setting of optic neuritis, however, is made by imaging of the brain, not of the optic nerves themselves. MRI of the brain provides information that can change the management of optic neuritis and yields prognostic information regarding the patient's future risk of developing MS. The most valuable predictor of the development of subsequent MS is the presence of white matter abnormalities. Between 27% and 70% of patients (in various studies) with isolated optic neuritis showed abnormal MRI brain findings, as defined by the presence of two or more white matter lesions on T2-weighted images. Patients with two or more lesions may have up to an 80% chance of meeting criteria for MS within the next 5 years. 

A gradual recovery of visual acuity with time is characteristic of optic neuritis, although permanent residual deficits in color vision and contrast and brightness sensitivity are common. The symptoms of optic neuritis will usually resolve without medical treatment, although continuing to take regular MS disease-modulating medication is usually helpful. An intravenous steroid or oral prednisone is sometimes recommended to speed recovery. A 3- to 5-day course of high-dose (1 g) IV methylprednisolone, followed by a rapid oral taper of prednisone, has been shown to provide rapid recovery of symptoms in the acute phase. However, IV steroids do little to affect the ultimate visual acuity in patients with optic neuritis.

Typically, patients begin to recover 2-4 weeks after the onset of the vision loss. The optic nerve may take up to 6-12 months to heal completely, but most patients recover as much vision as they are going to within the first few months.

For patients with optic neuritis whose brain lesions on MRI indicate a high risk of developing clinically definite MS, treatment with immunomodulators may be considered. IV immunoglobulin treatment of acute optic neuritis has been shown to have no beneficial effect. In severe cases, plasma exchange may be considered.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ.

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme.

All of the above conditions can have ophthalmic manifestations, but the majority of optic neuritis cases seen in clinical practice are either sporadic or MS related. Optic neuritis is the first demyelinating event in approximately 20% of patients with MS. It develops in approximately 40% of MS patients during the course of their disease. 

Optic neuritis is characterized by loss of vision (or loss of color vision) in the affected eye and pain on movement of the eye (painful ophthalmoplegia). Less often, patients with optic neuritis may describe phosphenes (transient flashes of light or black squares) lasting from hours to months. Phosphenes may occur before or during an optic neuritis event or even several months after recovery.

The diagnosis of optic neuritis is usually made clinically, with direct imaging of the optic nerves showing evidence of optic disc swelling with blurred margins. The real contribution of imaging in the setting of optic neuritis, however, is made by imaging of the brain, not of the optic nerves themselves. MRI of the brain provides information that can change the management of optic neuritis and yields prognostic information regarding the patient's future risk of developing MS. The most valuable predictor of the development of subsequent MS is the presence of white matter abnormalities. Between 27% and 70% of patients (in various studies) with isolated optic neuritis showed abnormal MRI brain findings, as defined by the presence of two or more white matter lesions on T2-weighted images. Patients with two or more lesions may have up to an 80% chance of meeting criteria for MS within the next 5 years. 

A gradual recovery of visual acuity with time is characteristic of optic neuritis, although permanent residual deficits in color vision and contrast and brightness sensitivity are common. The symptoms of optic neuritis will usually resolve without medical treatment, although continuing to take regular MS disease-modulating medication is usually helpful. An intravenous steroid or oral prednisone is sometimes recommended to speed recovery. A 3- to 5-day course of high-dose (1 g) IV methylprednisolone, followed by a rapid oral taper of prednisone, has been shown to provide rapid recovery of symptoms in the acute phase. However, IV steroids do little to affect the ultimate visual acuity in patients with optic neuritis.

Typically, patients begin to recover 2-4 weeks after the onset of the vision loss. The optic nerve may take up to 6-12 months to heal completely, but most patients recover as much vision as they are going to within the first few months.

For patients with optic neuritis whose brain lesions on MRI indicate a high risk of developing clinically definite MS, treatment with immunomodulators may be considered. IV immunoglobulin treatment of acute optic neuritis has been shown to have no beneficial effect. In severe cases, plasma exchange may be considered.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ.

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

For almost all of us, “screen time”—time spent using a device with a screen such as a smartphone, computer, television, or video game console—has become a large part of our daily lives. This is very much the case for children and adolescents. In the United States, children ages 8 to 12 years spend an average of 4 to 6 hours each day watching or using screens, and teens spend up to 9 hours.¹ Because young people are continually adopting newer forms of entertainment and technologies, new digital technologies are an ongoing source of concern for parents and clinicians alike.² Studies have suggested that excessive screen time is associated with numerous psychiatric symptoms and disorders, including poor sleep, weight gain, anxiety, depression, and attention-deficit/hyperactive disorder.^3,4 However, a recent systematic review and meta-analysis found that individuals’ self-reports of media use were rarely an accurate reflection of their actual, logged media use, and that measures of problematic media use had an even weaker association with usage logs.⁵ Therefore, it is crucial to have an accurate understanding of how children and adolescents are affected by new technologies. In this article, we discuss a recent study that investigated variations in adolescents’ mental health over time, and the association of their mental health and their use of digital technologies.

Results were mixed

Vuorre et al⁶ conducted a study to examine a possible shift in the associations between adolescents’ technology use and mental health outcomes. To investigate whether technology engagement and mental health outcomes changed over time, these researchers evaluated the impact not only of smartphones and social media, but also of television, which in the mid- to late-20th century elicited comparable levels of academic, public, and policy concern about its potential impact on child development. They analyzed data from 3 large-scale studies of adolescents living in the United States (Monitoring the Future and Youth Risk Behavior Surveillance System) and the United Kingdom (Understanding Society) that included a total of 430,561 participants.

The results were mixed across types of technology and mental health outcomes. Television and social media were found to have a direct correlation with conduct problems and emotional problems. Suicidal ideation and behavior were associated with digital device use; however, no correlation was found between depression and technology use. Regarding social media use, researchers found that its association with conduct problems remained stable, decreased with depression, and increased with emotional problems. The magnitudes of the observed changes over time were small. These researchers concluded there is “little evidence for increases in the associations between adolescents’ technology engagement and mental health [problems]” and “drawing firm conclusions about changes in ... associations with mental health may be premature.”⁶

Future directions

The study by Vuorre et al⁶ has opened the door to better analysis of the association between screen use and mental health outcomes. More robust, detailed studies are required to fully understand the varying impact of technologies on the lives of children and adolescents. Collaborative efforts by technology companies and researchers can help to determine the impact of technology on young people’s mental health.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

For almost all of us, “screen time”—time spent using a device with a screen such as a smartphone, computer, television, or video game console—has become a large part of our daily lives. This is very much the case for children and adolescents. In the United States, children ages 8 to 12 years spend an average of 4 to 6 hours each day watching or using screens, and teens spend up to 9 hours.¹ Because young people are continually adopting newer forms of entertainment and technologies, new digital technologies are an ongoing source of concern for parents and clinicians alike.² Studies have suggested that excessive screen time is associated with numerous psychiatric symptoms and disorders, including poor sleep, weight gain, anxiety, depression, and attention-deficit/hyperactive disorder.^3,4 However, a recent systematic review and meta-analysis found that individuals’ self-reports of media use were rarely an accurate reflection of their actual, logged media use, and that measures of problematic media use had an even weaker association with usage logs.⁵ Therefore, it is crucial to have an accurate understanding of how children and adolescents are affected by new technologies. In this article, we discuss a recent study that investigated variations in adolescents’ mental health over time, and the association of their mental health and their use of digital technologies.

Results were mixed

Vuorre et al⁶ conducted a study to examine a possible shift in the associations between adolescents’ technology use and mental health outcomes. To investigate whether technology engagement and mental health outcomes changed over time, these researchers evaluated the impact not only of smartphones and social media, but also of television, which in the mid- to late-20th century elicited comparable levels of academic, public, and policy concern about its potential impact on child development. They analyzed data from 3 large-scale studies of adolescents living in the United States (Monitoring the Future and Youth Risk Behavior Surveillance System) and the United Kingdom (Understanding Society) that included a total of 430,561 participants.

The results were mixed across types of technology and mental health outcomes. Television and social media were found to have a direct correlation with conduct problems and emotional problems. Suicidal ideation and behavior were associated with digital device use; however, no correlation was found between depression and technology use. Regarding social media use, researchers found that its association with conduct problems remained stable, decreased with depression, and increased with emotional problems. The magnitudes of the observed changes over time were small. These researchers concluded there is “little evidence for increases in the associations between adolescents’ technology engagement and mental health [problems]” and “drawing firm conclusions about changes in ... associations with mental health may be premature.”⁶

Future directions

The study by Vuorre et al⁶ has opened the door to better analysis of the association between screen use and mental health outcomes. More robust, detailed studies are required to fully understand the varying impact of technologies on the lives of children and adolescents. Collaborative efforts by technology companies and researchers can help to determine the impact of technology on young people’s mental health.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

For almost all of us, “screen time”—time spent using a device with a screen such as a smartphone, computer, television, or video game console—has become a large part of our daily lives. This is very much the case for children and adolescents. In the United States, children ages 8 to 12 years spend an average of 4 to 6 hours each day watching or using screens, and teens spend up to 9 hours.¹ Because young people are continually adopting newer forms of entertainment and technologies, new digital technologies are an ongoing source of concern for parents and clinicians alike.² Studies have suggested that excessive screen time is associated with numerous psychiatric symptoms and disorders, including poor sleep, weight gain, anxiety, depression, and attention-deficit/hyperactive disorder.^3,4 However, a recent systematic review and meta-analysis found that individuals’ self-reports of media use were rarely an accurate reflection of their actual, logged media use, and that measures of problematic media use had an even weaker association with usage logs.⁵ Therefore, it is crucial to have an accurate understanding of how children and adolescents are affected by new technologies. In this article, we discuss a recent study that investigated variations in adolescents’ mental health over time, and the association of their mental health and their use of digital technologies.

Results were mixed

Vuorre et al⁶ conducted a study to examine a possible shift in the associations between adolescents’ technology use and mental health outcomes. To investigate whether technology engagement and mental health outcomes changed over time, these researchers evaluated the impact not only of smartphones and social media, but also of television, which in the mid- to late-20th century elicited comparable levels of academic, public, and policy concern about its potential impact on child development. They analyzed data from 3 large-scale studies of adolescents living in the United States (Monitoring the Future and Youth Risk Behavior Surveillance System) and the United Kingdom (Understanding Society) that included a total of 430,561 participants.

The results were mixed across types of technology and mental health outcomes. Television and social media were found to have a direct correlation with conduct problems and emotional problems. Suicidal ideation and behavior were associated with digital device use; however, no correlation was found between depression and technology use. Regarding social media use, researchers found that its association with conduct problems remained stable, decreased with depression, and increased with emotional problems. The magnitudes of the observed changes over time were small. These researchers concluded there is “little evidence for increases in the associations between adolescents’ technology engagement and mental health [problems]” and “drawing firm conclusions about changes in ... associations with mental health may be premature.”⁶

Future directions

The study by Vuorre et al⁶ has opened the door to better analysis of the association between screen use and mental health outcomes. More robust, detailed studies are required to fully understand the varying impact of technologies on the lives of children and adolescents. Collaborative efforts by technology companies and researchers can help to determine the impact of technology on young people’s mental health.

On the basis of the patient's presentation and imaging results, the likely diagnosis is non–small cell cancer (NSCLC) of an adenocarcinoma subtype. NSCLC makes up about 80% of all lung cancer cases. Adenocarcinoma in particular is the most common type of lung cancer in the United States, accounting for about 40% of cases, and it is the most common histology among nonsmokers. Women are more likely to develop this subtype of NSCLC and are generally younger when they present with symptoms. This type of cancer arises from the bronchial mucosal glands and usually develops in a peripheral location within the lung. 

In the course of workup, immunohistochemical (IHC) analyses are used to identify tumor type and lineage (adenocarcinoma, squamous cell carcinoma, metastatic malignancy, or primary pleural mesothelioma). Separate IHC analyses are then used to guide treatment decisions, identifying whether ALK inhibitor therapy or programmed cell death protein ligand 1 (PD-L1) inhibitor therapy would be appropriate.

Tissue should also be conserved for molecular testing. NCCN guidelines advise that all patients with adenocarcinoma should be tested for EGFR mutations, and DNA mutational analysis is the preferred method for assessment. Patients should also undergo routine biomarker testing, with an eye toward ALK, RET, and ROS1 rearrangements, BRAF mutations, c-MET and exon 14 skipping mutations, and PD-L1 expression levels. For patients with metastatic NSCLC, PD-L1 IHC testing is recommended.

Most cases of lung cancer are diagnosed at a late stage, when symptoms have already begun to manifest. Of note, however, women with adenocarcinoma are more likely to present with localized disease. Treatment is largely influenced by the presence of targetable mutations. Among adenocarcinoma cases, the most common mutations are in the EGFR and KRAS genes.

For patients who are EGFR mutation positive (exon 10 deletion or L858R), osimertinib is the recommended first-line therapy. For patients who are positive for the EGFR exon 20 insertion mutation, initial systemic therapy options for adenocarcinoma are appropriate; the preferred regimen being pembrolizumab-carboplatin-pemetrexed if there are no contraindications to programmed cell death protein 1 (PD-1) or PD-L1 inhibitors.

KRAS mutations, unlike EGFR mutations, are associated with smoking. Because overlapping targetable alterations are uncommon, identification of KRAS mutations suggests that these patients will not benefit from additional molecular testing. Again, initial systemic therapy options for adenocarcinoma are appropriate, but the presence of KRAS mutation predicts a poor response to EGFR tyrosine kinase inhibitors. The FDA approved a KRAS inhibitor in June 2021 and immune checkpoint inhibitors appear to be beneficial in this population.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

On the basis of the patient's presentation and imaging results, the likely diagnosis is non–small cell cancer (NSCLC) of an adenocarcinoma subtype. NSCLC makes up about 80% of all lung cancer cases. Adenocarcinoma in particular is the most common type of lung cancer in the United States, accounting for about 40% of cases, and it is the most common histology among nonsmokers. Women are more likely to develop this subtype of NSCLC and are generally younger when they present with symptoms. This type of cancer arises from the bronchial mucosal glands and usually develops in a peripheral location within the lung. 

In the course of workup, immunohistochemical (IHC) analyses are used to identify tumor type and lineage (adenocarcinoma, squamous cell carcinoma, metastatic malignancy, or primary pleural mesothelioma). Separate IHC analyses are then used to guide treatment decisions, identifying whether ALK inhibitor therapy or programmed cell death protein ligand 1 (PD-L1) inhibitor therapy would be appropriate.

Tissue should also be conserved for molecular testing. NCCN guidelines advise that all patients with adenocarcinoma should be tested for EGFR mutations, and DNA mutational analysis is the preferred method for assessment. Patients should also undergo routine biomarker testing, with an eye toward ALK, RET, and ROS1 rearrangements, BRAF mutations, c-MET and exon 14 skipping mutations, and PD-L1 expression levels. For patients with metastatic NSCLC, PD-L1 IHC testing is recommended.

Most cases of lung cancer are diagnosed at a late stage, when symptoms have already begun to manifest. Of note, however, women with adenocarcinoma are more likely to present with localized disease. Treatment is largely influenced by the presence of targetable mutations. Among adenocarcinoma cases, the most common mutations are in the EGFR and KRAS genes.

For patients who are EGFR mutation positive (exon 10 deletion or L858R), osimertinib is the recommended first-line therapy. For patients who are positive for the EGFR exon 20 insertion mutation, initial systemic therapy options for adenocarcinoma are appropriate; the preferred regimen being pembrolizumab-carboplatin-pemetrexed if there are no contraindications to programmed cell death protein 1 (PD-1) or PD-L1 inhibitors.

KRAS mutations, unlike EGFR mutations, are associated with smoking. Because overlapping targetable alterations are uncommon, identification of KRAS mutations suggests that these patients will not benefit from additional molecular testing. Again, initial systemic therapy options for adenocarcinoma are appropriate, but the presence of KRAS mutation predicts a poor response to EGFR tyrosine kinase inhibitors. The FDA approved a KRAS inhibitor in June 2021 and immune checkpoint inhibitors appear to be beneficial in this population.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

On the basis of the patient's presentation and imaging results, the likely diagnosis is non–small cell cancer (NSCLC) of an adenocarcinoma subtype. NSCLC makes up about 80% of all lung cancer cases. Adenocarcinoma in particular is the most common type of lung cancer in the United States, accounting for about 40% of cases, and it is the most common histology among nonsmokers. Women are more likely to develop this subtype of NSCLC and are generally younger when they present with symptoms. This type of cancer arises from the bronchial mucosal glands and usually develops in a peripheral location within the lung. 

In the course of workup, immunohistochemical (IHC) analyses are used to identify tumor type and lineage (adenocarcinoma, squamous cell carcinoma, metastatic malignancy, or primary pleural mesothelioma). Separate IHC analyses are then used to guide treatment decisions, identifying whether ALK inhibitor therapy or programmed cell death protein ligand 1 (PD-L1) inhibitor therapy would be appropriate.

Tissue should also be conserved for molecular testing. NCCN guidelines advise that all patients with adenocarcinoma should be tested for EGFR mutations, and DNA mutational analysis is the preferred method for assessment. Patients should also undergo routine biomarker testing, with an eye toward ALK, RET, and ROS1 rearrangements, BRAF mutations, c-MET and exon 14 skipping mutations, and PD-L1 expression levels. For patients with metastatic NSCLC, PD-L1 IHC testing is recommended.

Most cases of lung cancer are diagnosed at a late stage, when symptoms have already begun to manifest. Of note, however, women with adenocarcinoma are more likely to present with localized disease. Treatment is largely influenced by the presence of targetable mutations. Among adenocarcinoma cases, the most common mutations are in the EGFR and KRAS genes.

For patients who are EGFR mutation positive (exon 10 deletion or L858R), osimertinib is the recommended first-line therapy. For patients who are positive for the EGFR exon 20 insertion mutation, initial systemic therapy options for adenocarcinoma are appropriate; the preferred regimen being pembrolizumab-carboplatin-pemetrexed if there are no contraindications to programmed cell death protein 1 (PD-1) or PD-L1 inhibitors.

KRAS mutations, unlike EGFR mutations, are associated with smoking. Because overlapping targetable alterations are uncommon, identification of KRAS mutations suggests that these patients will not benefit from additional molecular testing. Again, initial systemic therapy options for adenocarcinoma are appropriate, but the presence of KRAS mutation predicts a poor response to EGFR tyrosine kinase inhibitors. The FDA approved a KRAS inhibitor in June 2021 and immune checkpoint inhibitors appear to be beneficial in this population.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck