MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Bruce Jancin/Frontline Medical News

“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.

There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.

The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.

So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.

SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.

The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.

“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”

First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.

“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.

Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.

“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.

Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.

“A lot of our cirrhotic patients are on both,” she noted.

Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.

Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.

“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.

FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).

“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.

Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.

“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.

MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Bruce Jancin/Frontline Medical News

“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.

There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.

The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.

So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.

SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.

The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.

“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”

First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.

“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.

Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.

“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.

Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.

“A lot of our cirrhotic patients are on both,” she noted.

Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.

Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.

“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.

FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).

“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.

Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.

“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.

MAUI, HAWAII – Recognition and effective treatment of small intestinal bowel overgrowth – aka, SIBO – is a highly practical skillset for nongastroenterologists to possess, Uma Mahadevan, MD, said at the 2018 Rheumatology Winter Clinical Symposium.

SIBO is a common accompaniment to a range of chronic diseases, especially as patients age. And it’s not a condition that warrants referral to a gastroenterologist, according to Dr. Mahadevan, professor of medicine and medical director of the Center for Colitis and Crohn’s Disease at the University of California, San Francisco.

Bruce Jancin/Frontline Medical News

“To diagnose SIBO properly you need to do a carbohydrate breath test. Those tests are notoriously inaccurate, and it’s not worth it. We just treat. If we think you have SIBO, you do a course of rifaximin. And you can do the same,” she told her audience of rheumatologists.

There is an alternative diagnostic test. It involves obtaining a jejunal aspirate culture that demonstrates a bacterial concentration of more than 1,000 colony-forming units/mL. That’s an invasive and expensive test. Given how common SIBO symptoms are in patients with various underlying chronic diseases and the highly favorable risk/benefit ratio of a course of rifaximin, it’s entirely reasonable to skip formal diagnostic testing and treat empirically when the clinical picture is consistent with SIBO, according to the gastroenterologist.

The etiology of SIBO involves diminished intestinal motility and altered mucosal defenses. With reduced GI motility, the small bowel can’t get cleared of debris efficiently. Colonic microbes grab a foothold and bloom. Conditions marked by diminished intestinal motility – and high rates of SIBO – include scleroderma, diabetes, irritable bowel syndrome, chronic pancreatitis, cirrhosis, common variable immunodeficiency, HIV infection, and radiation enteritis. Small bowel diverticula are a setup for SIBO. Long-term proton pump inhibitor–therapy fosters hypochlorydia, which promotes SIBO. Opioid therapy is another common cause of SIBO.

So is bariatric surgery. “Bariatric surgery has caused so much iatrogenic GI disease, it’s just amazing. There is bacterial overgrowth in that population, and it’s a lot more complex than basic SIBO,” Dr. Mahadevan said.

SIBO causes malabsorption across the intestinal microvillus membrane as a result of damage to enterocytes, as well as impaired digestion in the intestinal lumen.

The presenting hallmark symptoms of SIBO are bloating, flatulence, early satiety, abdominal discomfort, and in some cases chronic diarrhea.

“You get a lot of gas and bloating. Patients will say, ‘I eat a small amount and feel full; I look like I’m pregnant; I have a lot of gas. What’s wrong with me?’ Chances are they have SIBO,” Dr. Mahadevan said. “The older you get the more SIBO you have.”

First-line treatment, aimed at diminishing small bowel bacteria, is rifaximin at 550 mg three times per day for 10-14 days.

“This is a very low-risk antibiotic. And it’s very effective for SIBO, but patients may need multiple courses,” according to the gastroenterologist.

Indeed, 40% of patients will experience recurrent SIBO symptoms within 9 months after a round of rifaximin. Recurrences are more common in patients on chronic proton pump–inhibitor therapy, the elderly, and those who have undergone appendectomy. Such patients may need another course of rifaximin once or twice per year.

“If they need rifaximin every 6 months, fine. Patients will be so grateful to you for that course of rifaximin,” Dr. Mahadevan said.

Patients with methane-predominant bacterial overgrowth, as opposed to hydrogen-predominant overgrowth, often benefit from concomitant neomycin at 500 mg twice per day along with their 10-14 days of rifaximin.

“A lot of our cirrhotic patients are on both,” she noted.

Alternatives to rifaximin include amoxicillin/clavulanic acid in combination with metronidazole.

Two measures she routinely recommends to forestall recurrent SIBO are to have patients start probiotics after a course of rifaximin, and also to try the low-FODMAP (fermentable oligo-di-monosaccharides and polyols) diet. The evidence base in SIBO is weak, but the anecdotal experience has been strongly positive.

“These are two interventions you can provide to your patients with a lot of bloating and gas. It’ll make them feel much, much better,” the gastroenterologist said.

FODMAPs are short-chain carbohydrates, and the low-FODMAP diet is an elimination diet. The first 6 weeks are highly restrictive, then the foods on the high FODMAP list are reintroduced one at a time until the offenders are identified. The low-FODMAP diet hasn’t been conclusively proven effective for SIBO in a randomized clinical trial, but it does have a compelling evidence base for treatment of irritable bowel syndrome diarrhea (J Gastroenterol Hepatol. 2010 Feb;25[2]:252-8).

“Anecdotally, the use of a low-FODMAP diet in patients with bloating and gas is very effective as well. Patients have a good deal of success with it,” she said.

Audience members were eager to learn what particular specific probiotic microorganism Dr. Madahaven recommends.

“I think the more we understand the microbiome, the further away I’m going from specific probiotics because it’s just too complex for any one probiotic to be effective. I tell patients to try to get it from their diet: yogurt or kefir with live bacteria. That’s what I use now,” she replied.

Psoriasis is a chronic inflammatory disease that affects approximately 2% to 3% of the US population.¹ Patients with psoriasis are more likely to have cardiovascular risk factors (eg, obesity, metabolic syndrome) than individuals without psoriasis.² In fact, recent evidence has suggested that a diagnosis of psoriasis is an independent risk factor for cardiometabolic diseases including diabetes, major adverse cardiovascular events, and obesity.³ Given the well-recognized health benefits of physical activity and the associated reduction in coronary heart disease risk,⁴ patients with psoriasis specifically may benefit from regular participation in physical activity. Thus, an enhanced understanding of the relationship between psoriasis and vigorous physical activity would help determine the role of initiating and recommending interventions that implement physical activity for patients with psoriasis. A review was conducted to determine the relationship between psoriasis and vigorous physical activity.

Methods

An English-language literature search of PubMed articles indexed for MEDLINE (January 1, 1946–October 15, 2017) as well as articles in the Embase database (January 1, 1947–October 15, 2017) and Cochrane Library (January 1, 1992–October 15, 2017) using the terms psoriasis and physical activity was performed. The search strategy was established based on a prior review of vigorous physical activity in eczema.⁵ The article titles and/or abstracts were reviewed, and the studies were excluded if they did not evaluate physical activity in patients with psoriasis. Studies without a control group also were excluded. Articles on patients with psoriatic arthritis and studies that involved modification of dietary intake also were excluded.

Two reviewers (M.A. and E.B.L.) independently extracted data from the studies and compiled the results. The following factors were included in the data extracted: study year, location, and design; method of diagnosis of psoriasis; total number of patients included in the study; and age, gender, and level of physical activity of the study patients. Level of physical activity was the exposure, and diagnosis of psoriasis was the dependent variable. Physical activity was defined differently across the studies that were evaluated. To determine study quality, we implemented the Newcastle–Ottawa Scale (NOS), a 9-star scoring system that includes items such as selection criteria, comparability, and study outcome.⁶ Studies with an NOS score of 7 or higher were included in the meta-analysis.

Results

The literature search generated 353 nonduplicate articles. A thorough review of the articles yielded 4 studies that were incorporated in the final analysis.^7-10 We aimed to perform a meta-analysis; however, only 1 of the studies included in the final analysis had an NOS score of 7 or higher along with adequate data to be incorporated into our study.¹⁰ As a result, the meta-analysis was converted to a regular review.

The cross-sectional study we reviewed, which had an NOS score of 7, included males and females in the United States aged 20 to 59 years.¹⁰ Data were collected using the population-based National Health and Nutrition Examination Survey from 2003 to 2006. The survey measured the likelihood of participation in leisure-time moderate to vigorous physical activity (MVPA) and metabolic equivalent task (MET) minutes of MVPA in the past 30 days. Of 6549 participants, 385 were excluded from the analysis due to missing values for 1 or more of the study variables. Of the remaining 6164 participants, 84 (1.4%) reported having a diagnosis of psoriasis with few or no psoriasis patches at the time of the survey, and 71 (1.2%) reported having a diagnosis of psoriasis with few to extensive patches at the time of the survey.¹⁰

Participants with psoriasis were less likely to participate in MVPA in the previous 30 days compared to participants without psoriasis, but the association was not statistically significant.¹⁰ The study demonstrated that, on average, participants with psoriasis spent 31% (95% confidence interval [CI], −0.57 to −0.05) fewer MET minutes on leisure-time MVPA versus participants without psoriasis; however, this association was not statistically significant. It is important to note that the diagnosis of psoriasis was self-reported, and measures of disease duration or areas of involvement were not incorporated.

Comment

Our review revealed that vigorous physical activity may be reduced in patients with psoriasis compared to those without psoriasis. Initially, we aimed to perform a systematic review of the literature; however, only 1 study met the criteria for the systematic review, highlighting the need for more robust studies evaluating this subject.

Do et al¹⁰ demonstrated that psoriasis patients were less likely to participate in MVPA, but the findings were not statistically significant. Of those who participated in MVPA, MET minutes were fewer among patients with few to extensive skin lesions compared to those without psoriasis. The investigators suggested that psoriasis patients with more severe disease tend to exercise less and ultimately would benefit from regular vigorous physical activity.

Frankel et al⁷ performed a prospective cohort study in US women to evaluate the role of physical activity in preventing psoriasis. The investigators reported that the most physically active quintile had a lower multivariate relative risk of psoriasis (0.72; 95% CI, 0.59–0.89; P<.001 for trend) compared to the least active quintile.⁷ Additionally, vigorous physical activity, which was defined as 6 or more MET minutes, was associated with a significantly lower risk of incident psoriasis (0.66; 95% CI, 0.54–0.81; P<.001 for trend), which maintained significance after adjusting for body mass index (BMI). The investigators suggested that, by decreasing chronic inflammation and lowering levels of proinflammatory cytokines, vigorous physical activity may reduce the risk of psoriasis development in women.⁷ It is plausible that vigorous physical activity modifies the state of chronic inflammation, which could subsequently reduce the risk of developing psoriasis; however, further long-term, randomized, prospective studies are needed to verify the relationship between physical activity and development of psoriasis.

Torres et al⁸ performed a cross-sectional questionnaire study to assess physical activity in patients with severe psoriasis (defined as >10% body surface area involvement and/or disease requiring systemic therapy or phototherapy) versus healthy controls. Physical activity level was measured using the International Physical Activity Questionnaire. The odds ratio of low-level physical activity compared to non–low-level physical activity among psoriasis patients versus controls was 3.42 (95% CI, 1.47–7.91; P=.002). Additionally, the average total MET minutes of psoriasis patients were significantly reduced compared to those of the healthy controls (P=.001). Thus, the investigators suggested that vigorous physical activity is less likely in psoriasis patients, which may contribute to the increased risk of cardiovascular disease in this population.⁸ Vigorous physical activity would benefit patients with psoriasis to help lower the chronic state of inflammation and cardiometabolic comorbidities.

Demirel et al⁹ performed a study to compare aerobic exercise capacity and daily physical activity level in psoriasis patients (n=30) compared to controls (n=30). Daily physical activity, measured with an accelerometer, was significantly higher in male patients with psoriasis compared to controls (P=.021). No significant difference was reported in maximal aerobic capacity in both male and female psoriasis patients versus controls. The investigators suggested that the level of daily physical activity is not limited in psoriasis patients, yet the small sample size may limit the generalizability of the study.

The ability to dissipate heat during exercise seems to be diminished in patients with psoriasis. Specifically, it has been suggested that psoriasis lesions interfere with normal perspiration.¹¹ Moreover, joint involvement in patients with psoriatic arthritis may lead to physical functional disabilities that can interfere with the ability of these patients to participate in regular physical activity.^12-14 For this reason, our review excluded articles that evaluated patients with psoriatic arthritis. Despite this exclusion, it is important to consider that comorbid psoriatic arthritis in clinical practice may impede patients with psoriasis from participating in physical activity. Additionally, various social aspects also may limit physical activity in psoriasis patients; for instance, psoriasis patients often avoid activities that involve increased exposure of the skin (eg, communal showers, wearing sports attire).¹⁵

Furthermore, obese psoriasis patients are less likely to exercise compared to obese individuals without psoriasis.¹⁶ In patients with higher BMI, the risk of psoriasis is increased.¹⁷ A systematic review suggested that weight loss may improve psoriasis severity.¹⁸ Bariatric surgery also may improve psoriasis.¹⁹ Moreover, obesity may interfere with response to biologic therapies for psoriasis. Specifically, higher BMI is linked with lower response to fixed-dose biologic therapies compared to weight-based biologic options (eg, infliximab).^20,21

Conclusion

Given the increased risk of myocardial infarction in patients with psoriasis, it is important to recognize the barriers to physical activity that psoriasis patients face.²² Due to the considerable health benefits associated with regular physical activity, physicians should encourage patients with psoriasis to participate in physical activity as tolerated. Of note, the studies included in this review varied in their definitions of psoriasis disease severity and measures of physical activity level. Long-term, randomized, prospective studies are needed to clarify the relationship between psoriasis and physical activity. Evidence from these studies would help guide clinical recommendations regarding the role of physical activity for patients with psoriasis.

Psoriasis is a chronic inflammatory disease that affects approximately 2% to 3% of the US population.¹ Patients with psoriasis are more likely to have cardiovascular risk factors (eg, obesity, metabolic syndrome) than individuals without psoriasis.² In fact, recent evidence has suggested that a diagnosis of psoriasis is an independent risk factor for cardiometabolic diseases including diabetes, major adverse cardiovascular events, and obesity.³ Given the well-recognized health benefits of physical activity and the associated reduction in coronary heart disease risk,⁴ patients with psoriasis specifically may benefit from regular participation in physical activity. Thus, an enhanced understanding of the relationship between psoriasis and vigorous physical activity would help determine the role of initiating and recommending interventions that implement physical activity for patients with psoriasis. A review was conducted to determine the relationship between psoriasis and vigorous physical activity.

Methods

An English-language literature search of PubMed articles indexed for MEDLINE (January 1, 1946–October 15, 2017) as well as articles in the Embase database (January 1, 1947–October 15, 2017) and Cochrane Library (January 1, 1992–October 15, 2017) using the terms psoriasis and physical activity was performed. The search strategy was established based on a prior review of vigorous physical activity in eczema.⁵ The article titles and/or abstracts were reviewed, and the studies were excluded if they did not evaluate physical activity in patients with psoriasis. Studies without a control group also were excluded. Articles on patients with psoriatic arthritis and studies that involved modification of dietary intake also were excluded.

Two reviewers (M.A. and E.B.L.) independently extracted data from the studies and compiled the results. The following factors were included in the data extracted: study year, location, and design; method of diagnosis of psoriasis; total number of patients included in the study; and age, gender, and level of physical activity of the study patients. Level of physical activity was the exposure, and diagnosis of psoriasis was the dependent variable. Physical activity was defined differently across the studies that were evaluated. To determine study quality, we implemented the Newcastle–Ottawa Scale (NOS), a 9-star scoring system that includes items such as selection criteria, comparability, and study outcome.⁶ Studies with an NOS score of 7 or higher were included in the meta-analysis.

Results

The literature search generated 353 nonduplicate articles. A thorough review of the articles yielded 4 studies that were incorporated in the final analysis.^7-10 We aimed to perform a meta-analysis; however, only 1 of the studies included in the final analysis had an NOS score of 7 or higher along with adequate data to be incorporated into our study.¹⁰ As a result, the meta-analysis was converted to a regular review.

The cross-sectional study we reviewed, which had an NOS score of 7, included males and females in the United States aged 20 to 59 years.¹⁰ Data were collected using the population-based National Health and Nutrition Examination Survey from 2003 to 2006. The survey measured the likelihood of participation in leisure-time moderate to vigorous physical activity (MVPA) and metabolic equivalent task (MET) minutes of MVPA in the past 30 days. Of 6549 participants, 385 were excluded from the analysis due to missing values for 1 or more of the study variables. Of the remaining 6164 participants, 84 (1.4%) reported having a diagnosis of psoriasis with few or no psoriasis patches at the time of the survey, and 71 (1.2%) reported having a diagnosis of psoriasis with few to extensive patches at the time of the survey.¹⁰

Participants with psoriasis were less likely to participate in MVPA in the previous 30 days compared to participants without psoriasis, but the association was not statistically significant.¹⁰ The study demonstrated that, on average, participants with psoriasis spent 31% (95% confidence interval [CI], −0.57 to −0.05) fewer MET minutes on leisure-time MVPA versus participants without psoriasis; however, this association was not statistically significant. It is important to note that the diagnosis of psoriasis was self-reported, and measures of disease duration or areas of involvement were not incorporated.

Comment

Our review revealed that vigorous physical activity may be reduced in patients with psoriasis compared to those without psoriasis. Initially, we aimed to perform a systematic review of the literature; however, only 1 study met the criteria for the systematic review, highlighting the need for more robust studies evaluating this subject.

Do et al¹⁰ demonstrated that psoriasis patients were less likely to participate in MVPA, but the findings were not statistically significant. Of those who participated in MVPA, MET minutes were fewer among patients with few to extensive skin lesions compared to those without psoriasis. The investigators suggested that psoriasis patients with more severe disease tend to exercise less and ultimately would benefit from regular vigorous physical activity.

Frankel et al⁷ performed a prospective cohort study in US women to evaluate the role of physical activity in preventing psoriasis. The investigators reported that the most physically active quintile had a lower multivariate relative risk of psoriasis (0.72; 95% CI, 0.59–0.89; P<.001 for trend) compared to the least active quintile.⁷ Additionally, vigorous physical activity, which was defined as 6 or more MET minutes, was associated with a significantly lower risk of incident psoriasis (0.66; 95% CI, 0.54–0.81; P<.001 for trend), which maintained significance after adjusting for body mass index (BMI). The investigators suggested that, by decreasing chronic inflammation and lowering levels of proinflammatory cytokines, vigorous physical activity may reduce the risk of psoriasis development in women.⁷ It is plausible that vigorous physical activity modifies the state of chronic inflammation, which could subsequently reduce the risk of developing psoriasis; however, further long-term, randomized, prospective studies are needed to verify the relationship between physical activity and development of psoriasis.

Torres et al⁸ performed a cross-sectional questionnaire study to assess physical activity in patients with severe psoriasis (defined as >10% body surface area involvement and/or disease requiring systemic therapy or phototherapy) versus healthy controls. Physical activity level was measured using the International Physical Activity Questionnaire. The odds ratio of low-level physical activity compared to non–low-level physical activity among psoriasis patients versus controls was 3.42 (95% CI, 1.47–7.91; P=.002). Additionally, the average total MET minutes of psoriasis patients were significantly reduced compared to those of the healthy controls (P=.001). Thus, the investigators suggested that vigorous physical activity is less likely in psoriasis patients, which may contribute to the increased risk of cardiovascular disease in this population.⁸ Vigorous physical activity would benefit patients with psoriasis to help lower the chronic state of inflammation and cardiometabolic comorbidities.

Demirel et al⁹ performed a study to compare aerobic exercise capacity and daily physical activity level in psoriasis patients (n=30) compared to controls (n=30). Daily physical activity, measured with an accelerometer, was significantly higher in male patients with psoriasis compared to controls (P=.021). No significant difference was reported in maximal aerobic capacity in both male and female psoriasis patients versus controls. The investigators suggested that the level of daily physical activity is not limited in psoriasis patients, yet the small sample size may limit the generalizability of the study.

The ability to dissipate heat during exercise seems to be diminished in patients with psoriasis. Specifically, it has been suggested that psoriasis lesions interfere with normal perspiration.¹¹ Moreover, joint involvement in patients with psoriatic arthritis may lead to physical functional disabilities that can interfere with the ability of these patients to participate in regular physical activity.^12-14 For this reason, our review excluded articles that evaluated patients with psoriatic arthritis. Despite this exclusion, it is important to consider that comorbid psoriatic arthritis in clinical practice may impede patients with psoriasis from participating in physical activity. Additionally, various social aspects also may limit physical activity in psoriasis patients; for instance, psoriasis patients often avoid activities that involve increased exposure of the skin (eg, communal showers, wearing sports attire).¹⁵

Furthermore, obese psoriasis patients are less likely to exercise compared to obese individuals without psoriasis.¹⁶ In patients with higher BMI, the risk of psoriasis is increased.¹⁷ A systematic review suggested that weight loss may improve psoriasis severity.¹⁸ Bariatric surgery also may improve psoriasis.¹⁹ Moreover, obesity may interfere with response to biologic therapies for psoriasis. Specifically, higher BMI is linked with lower response to fixed-dose biologic therapies compared to weight-based biologic options (eg, infliximab).^20,21

Conclusion

Given the increased risk of myocardial infarction in patients with psoriasis, it is important to recognize the barriers to physical activity that psoriasis patients face.²² Due to the considerable health benefits associated with regular physical activity, physicians should encourage patients with psoriasis to participate in physical activity as tolerated. Of note, the studies included in this review varied in their definitions of psoriasis disease severity and measures of physical activity level. Long-term, randomized, prospective studies are needed to clarify the relationship between psoriasis and physical activity. Evidence from these studies would help guide clinical recommendations regarding the role of physical activity for patients with psoriasis.

Psoriasis is a chronic inflammatory disease that affects approximately 2% to 3% of the US population.¹ Patients with psoriasis are more likely to have cardiovascular risk factors (eg, obesity, metabolic syndrome) than individuals without psoriasis.² In fact, recent evidence has suggested that a diagnosis of psoriasis is an independent risk factor for cardiometabolic diseases including diabetes, major adverse cardiovascular events, and obesity.³ Given the well-recognized health benefits of physical activity and the associated reduction in coronary heart disease risk,⁴ patients with psoriasis specifically may benefit from regular participation in physical activity. Thus, an enhanced understanding of the relationship between psoriasis and vigorous physical activity would help determine the role of initiating and recommending interventions that implement physical activity for patients with psoriasis. A review was conducted to determine the relationship between psoriasis and vigorous physical activity.

Methods

An English-language literature search of PubMed articles indexed for MEDLINE (January 1, 1946–October 15, 2017) as well as articles in the Embase database (January 1, 1947–October 15, 2017) and Cochrane Library (January 1, 1992–October 15, 2017) using the terms psoriasis and physical activity was performed. The search strategy was established based on a prior review of vigorous physical activity in eczema.⁵ The article titles and/or abstracts were reviewed, and the studies were excluded if they did not evaluate physical activity in patients with psoriasis. Studies without a control group also were excluded. Articles on patients with psoriatic arthritis and studies that involved modification of dietary intake also were excluded.

Two reviewers (M.A. and E.B.L.) independently extracted data from the studies and compiled the results. The following factors were included in the data extracted: study year, location, and design; method of diagnosis of psoriasis; total number of patients included in the study; and age, gender, and level of physical activity of the study patients. Level of physical activity was the exposure, and diagnosis of psoriasis was the dependent variable. Physical activity was defined differently across the studies that were evaluated. To determine study quality, we implemented the Newcastle–Ottawa Scale (NOS), a 9-star scoring system that includes items such as selection criteria, comparability, and study outcome.⁶ Studies with an NOS score of 7 or higher were included in the meta-analysis.

Results

The literature search generated 353 nonduplicate articles. A thorough review of the articles yielded 4 studies that were incorporated in the final analysis.^7-10 We aimed to perform a meta-analysis; however, only 1 of the studies included in the final analysis had an NOS score of 7 or higher along with adequate data to be incorporated into our study.¹⁰ As a result, the meta-analysis was converted to a regular review.

The cross-sectional study we reviewed, which had an NOS score of 7, included males and females in the United States aged 20 to 59 years.¹⁰ Data were collected using the population-based National Health and Nutrition Examination Survey from 2003 to 2006. The survey measured the likelihood of participation in leisure-time moderate to vigorous physical activity (MVPA) and metabolic equivalent task (MET) minutes of MVPA in the past 30 days. Of 6549 participants, 385 were excluded from the analysis due to missing values for 1 or more of the study variables. Of the remaining 6164 participants, 84 (1.4%) reported having a diagnosis of psoriasis with few or no psoriasis patches at the time of the survey, and 71 (1.2%) reported having a diagnosis of psoriasis with few to extensive patches at the time of the survey.¹⁰

Participants with psoriasis were less likely to participate in MVPA in the previous 30 days compared to participants without psoriasis, but the association was not statistically significant.¹⁰ The study demonstrated that, on average, participants with psoriasis spent 31% (95% confidence interval [CI], −0.57 to −0.05) fewer MET minutes on leisure-time MVPA versus participants without psoriasis; however, this association was not statistically significant. It is important to note that the diagnosis of psoriasis was self-reported, and measures of disease duration or areas of involvement were not incorporated.

Comment

Our review revealed that vigorous physical activity may be reduced in patients with psoriasis compared to those without psoriasis. Initially, we aimed to perform a systematic review of the literature; however, only 1 study met the criteria for the systematic review, highlighting the need for more robust studies evaluating this subject.

Do et al¹⁰ demonstrated that psoriasis patients were less likely to participate in MVPA, but the findings were not statistically significant. Of those who participated in MVPA, MET minutes were fewer among patients with few to extensive skin lesions compared to those without psoriasis. The investigators suggested that psoriasis patients with more severe disease tend to exercise less and ultimately would benefit from regular vigorous physical activity.

Frankel et al⁷ performed a prospective cohort study in US women to evaluate the role of physical activity in preventing psoriasis. The investigators reported that the most physically active quintile had a lower multivariate relative risk of psoriasis (0.72; 95% CI, 0.59–0.89; P<.001 for trend) compared to the least active quintile.⁷ Additionally, vigorous physical activity, which was defined as 6 or more MET minutes, was associated with a significantly lower risk of incident psoriasis (0.66; 95% CI, 0.54–0.81; P<.001 for trend), which maintained significance after adjusting for body mass index (BMI). The investigators suggested that, by decreasing chronic inflammation and lowering levels of proinflammatory cytokines, vigorous physical activity may reduce the risk of psoriasis development in women.⁷ It is plausible that vigorous physical activity modifies the state of chronic inflammation, which could subsequently reduce the risk of developing psoriasis; however, further long-term, randomized, prospective studies are needed to verify the relationship between physical activity and development of psoriasis.

Torres et al⁸ performed a cross-sectional questionnaire study to assess physical activity in patients with severe psoriasis (defined as >10% body surface area involvement and/or disease requiring systemic therapy or phototherapy) versus healthy controls. Physical activity level was measured using the International Physical Activity Questionnaire. The odds ratio of low-level physical activity compared to non–low-level physical activity among psoriasis patients versus controls was 3.42 (95% CI, 1.47–7.91; P=.002). Additionally, the average total MET minutes of psoriasis patients were significantly reduced compared to those of the healthy controls (P=.001). Thus, the investigators suggested that vigorous physical activity is less likely in psoriasis patients, which may contribute to the increased risk of cardiovascular disease in this population.⁸ Vigorous physical activity would benefit patients with psoriasis to help lower the chronic state of inflammation and cardiometabolic comorbidities.

Demirel et al⁹ performed a study to compare aerobic exercise capacity and daily physical activity level in psoriasis patients (n=30) compared to controls (n=30). Daily physical activity, measured with an accelerometer, was significantly higher in male patients with psoriasis compared to controls (P=.021). No significant difference was reported in maximal aerobic capacity in both male and female psoriasis patients versus controls. The investigators suggested that the level of daily physical activity is not limited in psoriasis patients, yet the small sample size may limit the generalizability of the study.

The ability to dissipate heat during exercise seems to be diminished in patients with psoriasis. Specifically, it has been suggested that psoriasis lesions interfere with normal perspiration.¹¹ Moreover, joint involvement in patients with psoriatic arthritis may lead to physical functional disabilities that can interfere with the ability of these patients to participate in regular physical activity.^12-14 For this reason, our review excluded articles that evaluated patients with psoriatic arthritis. Despite this exclusion, it is important to consider that comorbid psoriatic arthritis in clinical practice may impede patients with psoriasis from participating in physical activity. Additionally, various social aspects also may limit physical activity in psoriasis patients; for instance, psoriasis patients often avoid activities that involve increased exposure of the skin (eg, communal showers, wearing sports attire).¹⁵

Furthermore, obese psoriasis patients are less likely to exercise compared to obese individuals without psoriasis.¹⁶ In patients with higher BMI, the risk of psoriasis is increased.¹⁷ A systematic review suggested that weight loss may improve psoriasis severity.¹⁸ Bariatric surgery also may improve psoriasis.¹⁹ Moreover, obesity may interfere with response to biologic therapies for psoriasis. Specifically, higher BMI is linked with lower response to fixed-dose biologic therapies compared to weight-based biologic options (eg, infliximab).^20,21

Conclusion

Given the increased risk of myocardial infarction in patients with psoriasis, it is important to recognize the barriers to physical activity that psoriasis patients face.²² Due to the considerable health benefits associated with regular physical activity, physicians should encourage patients with psoriasis to participate in physical activity as tolerated. Of note, the studies included in this review varied in their definitions of psoriasis disease severity and measures of physical activity level. Long-term, randomized, prospective studies are needed to clarify the relationship between psoriasis and physical activity. Evidence from these studies would help guide clinical recommendations regarding the role of physical activity for patients with psoriasis.

ANAHEIM, CALIF.  –  Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.

Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.

This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”

She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.

The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.

Bruce Jancin/Frontline Medical News

Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.

In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.

Dr. Ball reported having no financial conflicts regarding her study.

bjancin@frontlinemedcom.com

SOURCE: Ball J. et al. AHA 2017, Abstract 16240.

ANAHEIM, CALIF.  –  Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.

Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.

This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”

She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.

The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.

Bruce Jancin/Frontline Medical News

Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.

In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.

Dr. Ball reported having no financial conflicts regarding her study.

bjancin@frontlinemedcom.com

SOURCE: Ball J. et al. AHA 2017, Abstract 16240.

ANAHEIM, CALIF.  –  Across the spectrum of cardiovascular disease, the more comorbid conditions a patient has, the higher the likelihood of mild cognitive impairment, Jocasta Ball, PhD, reported at the American Heart Association scientific sessions.

Indeed, her cross-sectional analysis of baseline data on 2,161 participants in five randomized controlled trials of nurse-led chronic disease management in cardiovascular disease (CVD) showed that for every 1-unit increase in the age-adjusted Charlson Comorbidity Index, the likelihood of mild cognitive impairment (MCI) jumped by 19%.

This novel observation has important clinical implications: “MCI is becoming increasingly recognized as exerting a powerful and negative impact on the risk, management, and prognosis of CVD patients,” explained Dr. Ball of the Baker Heart and Diabetes Institute in Melbourne. “Because MCI undermines a patient’s ability to comply with medical treatment and adds to patient complexity, it is critical [to identify] higher-risk individuals who require closer surveillance and improved early intervention.”

She added that the findings open up a whole new field of research aimed at developing new interventions to help patients with CVD and MCI stay on track with their heart disease treatment program.

The 2,161 subjects, mean age 70 years and two-thirds male, ranged across the full spectrum of cardiovascular disease, from mild to severe. All were screened for MCI by completing the Montreal Cognitive Assessment, or MoCA. A MoCA score below 26 out of a possible 30 is defined as MCI.

Bruce Jancin/Frontline Medical News

Forty-seven percent of subjects had MCI. They were older, with a mean age of 73 years versus 67 years; were more likely to have a history of stroke, by a margin of 20% versus 12%; had a 52% prevalence of atrial fibrillation versus 44%; and had a 50% prevalence of heart failure versus 39% in subjects with normal cognition. In addition, 48% of the MCI group screened positive for depressive symptoms versus 37% of those without MCI, and 28% of patients with MCI had type 2 diabetes, compared with 22% of those without MCI. Renal disease was also significantly more prevalent in the MCI group, by a margin of 21% versus 14%.

In a multivariate regression analysis, the strongest predictors of MCI in patients across the spectrum of CVD were current smoking, with a 2.5-fold increased risk compared with that of nonsmokers, and atrial fibrillation, with a 1.3-fold increased risk.

Dr. Ball reported having no financial conflicts regarding her study.

bjancin@frontlinemedcom.com

SOURCE: Ball J. et al. AHA 2017, Abstract 16240.

CASE Chronic pelvic pain from endometriosis

A 40-year-old woman (G0) has a 20-year history of chronic pelvic pain. Stage III endometriosis is diagnosed on laparoscopic excision of endometriotic tissue. Postoperative pain symptoms include dysmenorrhea and deep dyspareunia, and the patient is feeling anxious. Physical examination reveals a retroverted uterus, right adnexal fullness and tenderness, and tenderness on palpation of the right levator ani and right obturator internus; rectovaginal examination findings are unremarkable. The patient, though now engaged in a pelvic floor physical therapy program, has yet to achieve the pain control she desires. After reviewing the treatment strategies for endometriosis with the patient, she elects definitive surgical management with minimally invasive hysterectomy and salpingo-oophorectomy. What pre-, intra-, and postoperative pain management plan do you devise for this patient?

Chronic pelvic pain presents a unique clinical challenge, as pain typically is multifactorial, and several peripheral pain generators may be involved. Although surgery can be performed to manage anatomically based disease processes, it does not address pain from musculoskeletal or neuropathic sources. A complete medical history and a physical examination are of utmost importance in developing a comprehensive multimodal management plan that may include surgery as treatment for the pain.

The standard of care for surgery is a minimally invasive approach (vaginal, laparoscopic, or robot-assisted laparoscopic), as it causes the least amount of trauma. Benefits of minimally invasive surgery include shorter hospitalization and faster recovery, likely owing to improved perioperative pain control, decreased blood loss, and fewer infections. Although this approach minimizes surgical trauma and thereby helps decrease the surgical stress response, the patient experience can be optimized with use of enhanced recovery pathways (ERPs), a multimodal approach to perioperative care.

ERPs were initially proposed as a means of reducing the degree of surgical injury and the subsequent physiologic stress response.¹ This multimodal approach begins in the outpatient setting, includes preoperative and intraoperative modalities, and continues postoperatively. In patients with chronic pain, ERPs are even more important. Assigning “prehabilitation” and setting expectations for surgery goals are the first step in improving the patient experience. Intraoperative use of opioid-sparing anesthetics or regional anesthesia can improve recovery. After surgery, patients with chronic pain and/or opioid dependence receive medications on a schedule, along with short-interval follow-up. Ultimately, reducing acute postoperative pain may lower the risk of developing chronic pain.

In this article on patients with chronic pelvic pain, we highlight elements of ERPs within the framework of enhanced recovery after surgery. Many of the interventions proposed here also can be used to improve the surgical experience of patients without chronic pain.

Preadmission education, expectations, and optimization

Preoperative counseling for elective procedures generally occurs in the outpatient setting. Although discussion traditionally has covered the type of procedure and its associated risks, benefits, and alternatives, new guidelines suggest a more mindful and comprehensive approach is warranted. Individualized patient-centered education programs have a positive impact on the perioperative course, effecting reductions in preoperative anxiety, opioid requirements, and hospital length of stay.² From a pain management perspective, the clinician can take some time during preoperative counseling to inform the patient about the pain to be expected from surgery, the ways the pain will be managed intraoperatively and postoperatively, and the multimodal strategies that will be used throughout the patient’s stay² and that may allow for early discharge. Although preadmission counseling still should address expectations for the surgery, it also presents an opportunity both to assess the patient’s ability to cope with the physical and psychological stress of surgery and to offer the patient appropriate need-based interventions, such as prehabilitation and cognitive-behavioral therapy (CBT).

Prehabilitation is the process of increasing functional capacity before surgery in order to mitigate the stress of the surgery. Prehabilitation may involve aerobic exercise, strength training, or functional task training. The gynecologic surgery literature lacks prehabilitation data, but data in the colorectal literature support use of a prehabilitation program for patients having a scheduled colectomy, with improved postoperative recovery.³ Although the colectomy cohort predominantly included older men, the principle that guides program implementation is the same: improve recovery after the stress of abdominal surgery. Indeed, a patient who opts for an elective surgery may have to wait several weeks before undergoing the procedure, and during this period behavioral interventions can take effect. With postoperative complications occurring more often in patients with reduced functional capacity, the data support using prehabilitation to decrease the incidence of postoperative complications, particularly among the most vulnerable patients.⁴ However, a definitive recommendation on use of pelvic floor exercises as an adjunct to prehabilitation cannot be made.⁴ Successful prehabilitation takes at least 4 weeks and should be part of a multimodal program that addresses other behavioral risk factors that may negatively affect recovery.⁵ For example, current tobacco users have compromised pulmonary status and wound healing immediately after surgery, and use more opioids.⁶ Conversely, smoking cessation for as little as 4 weeks before surgery is associated with fewer complications.⁷ In addition, given that alcohol abuse may compromise the surgical stress response and increase the risk of opioid misuse, addressing alcohol abuse preoperatively may improve postoperative recovery.⁸

Treating mood disorders that coexist with chronic pain disorders is an important part of outpatient multimodal management—psychological intervention is a useful adjunct to prehabilitation in reducing perioperative anxiety and improving postoperative functional capacity.⁹ For patients who have chronic pain and are undergoing surgery, it is important to address any anxiety, depression, or poor coping skills (eg, pain catastrophizing) to try to reduce the postoperative pain experience and decrease the risk of chronic postsurgical pain (CPSP).^10,11

Before surgery, patients with chronic pain syndromes should be evaluated for emotional distress and pain coping ability. When possible, they should be referred to a pain psychologist, who can initiate CBT and other interventions. In addition, pain coping skills can be developed or reinforced to address preoperative anxiety and pain catastrophizing. These interventions, which may include use of visual imagery, breathing exercises, and other relaxation techniques, are applicable to the management of postoperative anxiety as well.

Read about preoperative multimodal analgesia and intra- and postoperative management.

Preoperative multimodal analgesia

Multimodal analgesia has several benefits. Simultaneous effects can be generated on multiple pain-related neurotransmitters, and a synergistic effect (eg, of acetaminophen and a nonsteroidal anti-inflammatory drug [NSAID]) can improve pain management. In addition, small doses of multiple medications can be given, instead of a large dose of a single medication. Of course, this strategy must be modified in elderly and patients with impaired renal function, who are at high risk for polypharmacy.

Preoperative administration of 3 medications—a selective cyclooxygenase 2 (COX-2) inhibitor, acetaminophen, and a gabapentinoid—is increasingly accepted as part of multimodal analgesia. The selective COX-2 inhibitor targets inflammatory prostaglandins and has anti-inflammatory and analgesic effects; acetaminophen, an effective analgesic with an unclear mechanism of action, can reduce postoperative opioid consumption¹² and works synergistically with NSAIDs¹³; and the gabapentinoid gabapentin has an analgesic effect likely contributing to decreased movement-related pain and subsequent improved functional recovery (data are mixed on whether continuing gabapentin after surgery prevents CPSP).¹⁴⁻¹⁶

Although serotonin and norepinephrine reuptake inhibitors (SNRIs) are commonly used in outpatient management of chronic pelvic pain, data suggest that their role in perioperative pain management is evolving. As SNRIs may reduce central nervous system (CNS) sensitization,¹⁷ their analgesic effect is thought to result from increased descending inhibitory tone in the CNS, which makes this class of medication ideal for patients with chronic neuropathic pain.¹⁵

Limited data also suggest a role for SNRIs in decreasing immediate postoperative pain and CPSP in high-risk patients. Studies of duloxetine use in the immediate perioperative period have found reduced postoperative acute pain and opioid use.^18,19 In addition, a short course of low-dose (37.5 mg) venlafaxine both before and after surgery has demonstrated a reduction in postoperative opioid use and a reduction in movement-related pain 6 months after surgery.²⁰

Intraoperative management

The surgical and anesthesia teams share the goal of optimizing both pain control and postoperative recovery. Surgical team members, who want longer-acting anesthetics for infiltration of incision sites, discuss with the anesthesiologist the appropriateness of using peripheral nerve blocks or neuraxial anesthesia, given the patient’s history and planned procedure. Anesthesia team members can improve anesthesia and minimize intraoperative opioid use through several methods, including total intravenous anesthesia,²¹ dexamethasone,²² ketorolac,²³ and intravenous ketamine. Ketamine, in particular, has a wide range of surgical applications and has been found to reduce postoperative pain, postoperative pain medication use, and the risk of CPSP.²

Incision sites should be infiltrated before and after surgery. Lidocaine traditionally is used for its rapid onset of action in reducing surgical site pain, but its short half-life may limit its applicability to postoperative pain. Recently, bupivacaine (half-life, 3.5 hours) and liposomal bupivacaine (24–34 hours) have gained more attention. Both of these medications appear to be as effective as lidocaine in reducing surgical site pain.²⁴

Transversus abdominis plane (TAP) blocks have been used as an adjunct in pain management during abdominopelvic surgery. Although initial data on postoperative pain and opioid use reductions with TAP blocks were inconclusive,²⁵ more recent data showed a role for TAP blocks in a multimodal approach for reducing opioid use during laparoscopic and open surgery.^26,27 Given the small number of studies on using liposomal bupivacaine for peripheral nerve blocks (eg, TAP blocks) in postoperative pain management, current data are inconclusive.²⁸

Postoperative management

The ERP approach calls for continuing multimodal analgesia after surgery—in most cases, scheduling early use of oral acetaminophen and ibuprofen, and providing short-acting, low-dose opioid analgesia as needed. All patients should be given a bowel regimen. Similar to undergoing prehabilitation for surgery, patients should prepare themselves for recovery. They should be encouraged to engage in early ambulation and oral intake and, when clinically appropriate, be given same-day discharge for minimally invasive surgical procedures.

Patients with chronic pain before surgery are at increased risk for suboptimal postoperative pain management, and those who are dependent on opioids require additional perioperative measures for adequate postoperative pain control. In these complicated cases, it is appropriate to enlist a pain specialist, potentially before surgery, to help plan perioperative and postoperative pain management.² Postoperative pain management for opioid-dependent patients should include pharmacologic and nonpharmacologic interventions, such as use of nonopioid medications (eg, gabapentin) and continuation of CBT. Patients with chronic pain should be closely followed up for assessment of postoperative pain control and recovery.

CASE Resolved

Surgical management is one aspect of the longer term multimodal pain management strategy for this patient. After preoperative pelvic floor physical therapy, she is receptive to starting a trial of an SNRI for her pain and mood symptoms. Both interventions allow for optimization of her preoperative physical and psychological status. Expectations are set that she will be discharged the day of surgery and that the surgery is but one component of her multimodal treatment plan. In addition, before surgery, she takes oral acetaminophen, gabapentin, and celecoxib—previously having had no contraindications to these medications. During surgery, bupivacaine is used for infiltration of all incision sites, and the anesthesia team administers ketamine and a TAP block. After surgery, the patient is prepared for same-day discharge and given the NSAIDs and acetaminophen she is scheduled to take over the next 72 hours. She is also given a limited prescription for oxycodone for breakthrough pain. An office visit 1 to 2 weeks after surgery is scheduled.

ERP strategies for surgical management of endometriosis have not only improved this patient’s postoperative recovery but also reduced her surgical stress response and subsequent transition to chronic postoperative pain. Many of the strategies used in this case are applicable to patients without chronic pain.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE Chronic pelvic pain from endometriosis

A 40-year-old woman (G0) has a 20-year history of chronic pelvic pain. Stage III endometriosis is diagnosed on laparoscopic excision of endometriotic tissue. Postoperative pain symptoms include dysmenorrhea and deep dyspareunia, and the patient is feeling anxious. Physical examination reveals a retroverted uterus, right adnexal fullness and tenderness, and tenderness on palpation of the right levator ani and right obturator internus; rectovaginal examination findings are unremarkable. The patient, though now engaged in a pelvic floor physical therapy program, has yet to achieve the pain control she desires. After reviewing the treatment strategies for endometriosis with the patient, she elects definitive surgical management with minimally invasive hysterectomy and salpingo-oophorectomy. What pre-, intra-, and postoperative pain management plan do you devise for this patient?

Chronic pelvic pain presents a unique clinical challenge, as pain typically is multifactorial, and several peripheral pain generators may be involved. Although surgery can be performed to manage anatomically based disease processes, it does not address pain from musculoskeletal or neuropathic sources. A complete medical history and a physical examination are of utmost importance in developing a comprehensive multimodal management plan that may include surgery as treatment for the pain.

The standard of care for surgery is a minimally invasive approach (vaginal, laparoscopic, or robot-assisted laparoscopic), as it causes the least amount of trauma. Benefits of minimally invasive surgery include shorter hospitalization and faster recovery, likely owing to improved perioperative pain control, decreased blood loss, and fewer infections. Although this approach minimizes surgical trauma and thereby helps decrease the surgical stress response, the patient experience can be optimized with use of enhanced recovery pathways (ERPs), a multimodal approach to perioperative care.

ERPs were initially proposed as a means of reducing the degree of surgical injury and the subsequent physiologic stress response.¹ This multimodal approach begins in the outpatient setting, includes preoperative and intraoperative modalities, and continues postoperatively. In patients with chronic pain, ERPs are even more important. Assigning “prehabilitation” and setting expectations for surgery goals are the first step in improving the patient experience. Intraoperative use of opioid-sparing anesthetics or regional anesthesia can improve recovery. After surgery, patients with chronic pain and/or opioid dependence receive medications on a schedule, along with short-interval follow-up. Ultimately, reducing acute postoperative pain may lower the risk of developing chronic pain.

In this article on patients with chronic pelvic pain, we highlight elements of ERPs within the framework of enhanced recovery after surgery. Many of the interventions proposed here also can be used to improve the surgical experience of patients without chronic pain.

Preadmission education, expectations, and optimization

Preoperative counseling for elective procedures generally occurs in the outpatient setting. Although discussion traditionally has covered the type of procedure and its associated risks, benefits, and alternatives, new guidelines suggest a more mindful and comprehensive approach is warranted. Individualized patient-centered education programs have a positive impact on the perioperative course, effecting reductions in preoperative anxiety, opioid requirements, and hospital length of stay.² From a pain management perspective, the clinician can take some time during preoperative counseling to inform the patient about the pain to be expected from surgery, the ways the pain will be managed intraoperatively and postoperatively, and the multimodal strategies that will be used throughout the patient’s stay² and that may allow for early discharge. Although preadmission counseling still should address expectations for the surgery, it also presents an opportunity both to assess the patient’s ability to cope with the physical and psychological stress of surgery and to offer the patient appropriate need-based interventions, such as prehabilitation and cognitive-behavioral therapy (CBT).

Prehabilitation is the process of increasing functional capacity before surgery in order to mitigate the stress of the surgery. Prehabilitation may involve aerobic exercise, strength training, or functional task training. The gynecologic surgery literature lacks prehabilitation data, but data in the colorectal literature support use of a prehabilitation program for patients having a scheduled colectomy, with improved postoperative recovery.³ Although the colectomy cohort predominantly included older men, the principle that guides program implementation is the same: improve recovery after the stress of abdominal surgery. Indeed, a patient who opts for an elective surgery may have to wait several weeks before undergoing the procedure, and during this period behavioral interventions can take effect. With postoperative complications occurring more often in patients with reduced functional capacity, the data support using prehabilitation to decrease the incidence of postoperative complications, particularly among the most vulnerable patients.⁴ However, a definitive recommendation on use of pelvic floor exercises as an adjunct to prehabilitation cannot be made.⁴ Successful prehabilitation takes at least 4 weeks and should be part of a multimodal program that addresses other behavioral risk factors that may negatively affect recovery.⁵ For example, current tobacco users have compromised pulmonary status and wound healing immediately after surgery, and use more opioids.⁶ Conversely, smoking cessation for as little as 4 weeks before surgery is associated with fewer complications.⁷ In addition, given that alcohol abuse may compromise the surgical stress response and increase the risk of opioid misuse, addressing alcohol abuse preoperatively may improve postoperative recovery.⁸

Treating mood disorders that coexist with chronic pain disorders is an important part of outpatient multimodal management—psychological intervention is a useful adjunct to prehabilitation in reducing perioperative anxiety and improving postoperative functional capacity.⁹ For patients who have chronic pain and are undergoing surgery, it is important to address any anxiety, depression, or poor coping skills (eg, pain catastrophizing) to try to reduce the postoperative pain experience and decrease the risk of chronic postsurgical pain (CPSP).^10,11

Before surgery, patients with chronic pain syndromes should be evaluated for emotional distress and pain coping ability. When possible, they should be referred to a pain psychologist, who can initiate CBT and other interventions. In addition, pain coping skills can be developed or reinforced to address preoperative anxiety and pain catastrophizing. These interventions, which may include use of visual imagery, breathing exercises, and other relaxation techniques, are applicable to the management of postoperative anxiety as well.

Read about preoperative multimodal analgesia and intra- and postoperative management.

Preoperative multimodal analgesia

Multimodal analgesia has several benefits. Simultaneous effects can be generated on multiple pain-related neurotransmitters, and a synergistic effect (eg, of acetaminophen and a nonsteroidal anti-inflammatory drug [NSAID]) can improve pain management. In addition, small doses of multiple medications can be given, instead of a large dose of a single medication. Of course, this strategy must be modified in elderly and patients with impaired renal function, who are at high risk for polypharmacy.

Preoperative administration of 3 medications—a selective cyclooxygenase 2 (COX-2) inhibitor, acetaminophen, and a gabapentinoid—is increasingly accepted as part of multimodal analgesia. The selective COX-2 inhibitor targets inflammatory prostaglandins and has anti-inflammatory and analgesic effects; acetaminophen, an effective analgesic with an unclear mechanism of action, can reduce postoperative opioid consumption¹² and works synergistically with NSAIDs¹³; and the gabapentinoid gabapentin has an analgesic effect likely contributing to decreased movement-related pain and subsequent improved functional recovery (data are mixed on whether continuing gabapentin after surgery prevents CPSP).¹⁴⁻¹⁶

Although serotonin and norepinephrine reuptake inhibitors (SNRIs) are commonly used in outpatient management of chronic pelvic pain, data suggest that their role in perioperative pain management is evolving. As SNRIs may reduce central nervous system (CNS) sensitization,¹⁷ their analgesic effect is thought to result from increased descending inhibitory tone in the CNS, which makes this class of medication ideal for patients with chronic neuropathic pain.¹⁵

Limited data also suggest a role for SNRIs in decreasing immediate postoperative pain and CPSP in high-risk patients. Studies of duloxetine use in the immediate perioperative period have found reduced postoperative acute pain and opioid use.^18,19 In addition, a short course of low-dose (37.5 mg) venlafaxine both before and after surgery has demonstrated a reduction in postoperative opioid use and a reduction in movement-related pain 6 months after surgery.²⁰

Intraoperative management

The surgical and anesthesia teams share the goal of optimizing both pain control and postoperative recovery. Surgical team members, who want longer-acting anesthetics for infiltration of incision sites, discuss with the anesthesiologist the appropriateness of using peripheral nerve blocks or neuraxial anesthesia, given the patient’s history and planned procedure. Anesthesia team members can improve anesthesia and minimize intraoperative opioid use through several methods, including total intravenous anesthesia,²¹ dexamethasone,²² ketorolac,²³ and intravenous ketamine. Ketamine, in particular, has a wide range of surgical applications and has been found to reduce postoperative pain, postoperative pain medication use, and the risk of CPSP.²

Incision sites should be infiltrated before and after surgery. Lidocaine traditionally is used for its rapid onset of action in reducing surgical site pain, but its short half-life may limit its applicability to postoperative pain. Recently, bupivacaine (half-life, 3.5 hours) and liposomal bupivacaine (24–34 hours) have gained more attention. Both of these medications appear to be as effective as lidocaine in reducing surgical site pain.²⁴

Transversus abdominis plane (TAP) blocks have been used as an adjunct in pain management during abdominopelvic surgery. Although initial data on postoperative pain and opioid use reductions with TAP blocks were inconclusive,²⁵ more recent data showed a role for TAP blocks in a multimodal approach for reducing opioid use during laparoscopic and open surgery.^26,27 Given the small number of studies on using liposomal bupivacaine for peripheral nerve blocks (eg, TAP blocks) in postoperative pain management, current data are inconclusive.²⁸

Postoperative management

The ERP approach calls for continuing multimodal analgesia after surgery—in most cases, scheduling early use of oral acetaminophen and ibuprofen, and providing short-acting, low-dose opioid analgesia as needed. All patients should be given a bowel regimen. Similar to undergoing prehabilitation for surgery, patients should prepare themselves for recovery. They should be encouraged to engage in early ambulation and oral intake and, when clinically appropriate, be given same-day discharge for minimally invasive surgical procedures.

Patients with chronic pain before surgery are at increased risk for suboptimal postoperative pain management, and those who are dependent on opioids require additional perioperative measures for adequate postoperative pain control. In these complicated cases, it is appropriate to enlist a pain specialist, potentially before surgery, to help plan perioperative and postoperative pain management.² Postoperative pain management for opioid-dependent patients should include pharmacologic and nonpharmacologic interventions, such as use of nonopioid medications (eg, gabapentin) and continuation of CBT. Patients with chronic pain should be closely followed up for assessment of postoperative pain control and recovery.

CASE Resolved

Surgical management is one aspect of the longer term multimodal pain management strategy for this patient. After preoperative pelvic floor physical therapy, she is receptive to starting a trial of an SNRI for her pain and mood symptoms. Both interventions allow for optimization of her preoperative physical and psychological status. Expectations are set that she will be discharged the day of surgery and that the surgery is but one component of her multimodal treatment plan. In addition, before surgery, she takes oral acetaminophen, gabapentin, and celecoxib—previously having had no contraindications to these medications. During surgery, bupivacaine is used for infiltration of all incision sites, and the anesthesia team administers ketamine and a TAP block. After surgery, the patient is prepared for same-day discharge and given the NSAIDs and acetaminophen she is scheduled to take over the next 72 hours. She is also given a limited prescription for oxycodone for breakthrough pain. An office visit 1 to 2 weeks after surgery is scheduled.

ERP strategies for surgical management of endometriosis have not only improved this patient’s postoperative recovery but also reduced her surgical stress response and subsequent transition to chronic postoperative pain. Many of the strategies used in this case are applicable to patients without chronic pain.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE Chronic pelvic pain from endometriosis

A 40-year-old woman (G0) has a 20-year history of chronic pelvic pain. Stage III endometriosis is diagnosed on laparoscopic excision of endometriotic tissue. Postoperative pain symptoms include dysmenorrhea and deep dyspareunia, and the patient is feeling anxious. Physical examination reveals a retroverted uterus, right adnexal fullness and tenderness, and tenderness on palpation of the right levator ani and right obturator internus; rectovaginal examination findings are unremarkable. The patient, though now engaged in a pelvic floor physical therapy program, has yet to achieve the pain control she desires. After reviewing the treatment strategies for endometriosis with the patient, she elects definitive surgical management with minimally invasive hysterectomy and salpingo-oophorectomy. What pre-, intra-, and postoperative pain management plan do you devise for this patient?

Chronic pelvic pain presents a unique clinical challenge, as pain typically is multifactorial, and several peripheral pain generators may be involved. Although surgery can be performed to manage anatomically based disease processes, it does not address pain from musculoskeletal or neuropathic sources. A complete medical history and a physical examination are of utmost importance in developing a comprehensive multimodal management plan that may include surgery as treatment for the pain.

The standard of care for surgery is a minimally invasive approach (vaginal, laparoscopic, or robot-assisted laparoscopic), as it causes the least amount of trauma. Benefits of minimally invasive surgery include shorter hospitalization and faster recovery, likely owing to improved perioperative pain control, decreased blood loss, and fewer infections. Although this approach minimizes surgical trauma and thereby helps decrease the surgical stress response, the patient experience can be optimized with use of enhanced recovery pathways (ERPs), a multimodal approach to perioperative care.

ERPs were initially proposed as a means of reducing the degree of surgical injury and the subsequent physiologic stress response.¹ This multimodal approach begins in the outpatient setting, includes preoperative and intraoperative modalities, and continues postoperatively. In patients with chronic pain, ERPs are even more important. Assigning “prehabilitation” and setting expectations for surgery goals are the first step in improving the patient experience. Intraoperative use of opioid-sparing anesthetics or regional anesthesia can improve recovery. After surgery, patients with chronic pain and/or opioid dependence receive medications on a schedule, along with short-interval follow-up. Ultimately, reducing acute postoperative pain may lower the risk of developing chronic pain.

In this article on patients with chronic pelvic pain, we highlight elements of ERPs within the framework of enhanced recovery after surgery. Many of the interventions proposed here also can be used to improve the surgical experience of patients without chronic pain.

Preadmission education, expectations, and optimization

Preoperative counseling for elective procedures generally occurs in the outpatient setting. Although discussion traditionally has covered the type of procedure and its associated risks, benefits, and alternatives, new guidelines suggest a more mindful and comprehensive approach is warranted. Individualized patient-centered education programs have a positive impact on the perioperative course, effecting reductions in preoperative anxiety, opioid requirements, and hospital length of stay.² From a pain management perspective, the clinician can take some time during preoperative counseling to inform the patient about the pain to be expected from surgery, the ways the pain will be managed intraoperatively and postoperatively, and the multimodal strategies that will be used throughout the patient’s stay² and that may allow for early discharge. Although preadmission counseling still should address expectations for the surgery, it also presents an opportunity both to assess the patient’s ability to cope with the physical and psychological stress of surgery and to offer the patient appropriate need-based interventions, such as prehabilitation and cognitive-behavioral therapy (CBT).

Prehabilitation is the process of increasing functional capacity before surgery in order to mitigate the stress of the surgery. Prehabilitation may involve aerobic exercise, strength training, or functional task training. The gynecologic surgery literature lacks prehabilitation data, but data in the colorectal literature support use of a prehabilitation program for patients having a scheduled colectomy, with improved postoperative recovery.³ Although the colectomy cohort predominantly included older men, the principle that guides program implementation is the same: improve recovery after the stress of abdominal surgery. Indeed, a patient who opts for an elective surgery may have to wait several weeks before undergoing the procedure, and during this period behavioral interventions can take effect. With postoperative complications occurring more often in patients with reduced functional capacity, the data support using prehabilitation to decrease the incidence of postoperative complications, particularly among the most vulnerable patients.⁴ However, a definitive recommendation on use of pelvic floor exercises as an adjunct to prehabilitation cannot be made.⁴ Successful prehabilitation takes at least 4 weeks and should be part of a multimodal program that addresses other behavioral risk factors that may negatively affect recovery.⁵ For example, current tobacco users have compromised pulmonary status and wound healing immediately after surgery, and use more opioids.⁶ Conversely, smoking cessation for as little as 4 weeks before surgery is associated with fewer complications.⁷ In addition, given that alcohol abuse may compromise the surgical stress response and increase the risk of opioid misuse, addressing alcohol abuse preoperatively may improve postoperative recovery.⁸

Treating mood disorders that coexist with chronic pain disorders is an important part of outpatient multimodal management—psychological intervention is a useful adjunct to prehabilitation in reducing perioperative anxiety and improving postoperative functional capacity.⁹ For patients who have chronic pain and are undergoing surgery, it is important to address any anxiety, depression, or poor coping skills (eg, pain catastrophizing) to try to reduce the postoperative pain experience and decrease the risk of chronic postsurgical pain (CPSP).^10,11

Before surgery, patients with chronic pain syndromes should be evaluated for emotional distress and pain coping ability. When possible, they should be referred to a pain psychologist, who can initiate CBT and other interventions. In addition, pain coping skills can be developed or reinforced to address preoperative anxiety and pain catastrophizing. These interventions, which may include use of visual imagery, breathing exercises, and other relaxation techniques, are applicable to the management of postoperative anxiety as well.

Read about preoperative multimodal analgesia and intra- and postoperative management.

Preoperative multimodal analgesia

Multimodal analgesia has several benefits. Simultaneous effects can be generated on multiple pain-related neurotransmitters, and a synergistic effect (eg, of acetaminophen and a nonsteroidal anti-inflammatory drug [NSAID]) can improve pain management. In addition, small doses of multiple medications can be given, instead of a large dose of a single medication. Of course, this strategy must be modified in elderly and patients with impaired renal function, who are at high risk for polypharmacy.

Preoperative administration of 3 medications—a selective cyclooxygenase 2 (COX-2) inhibitor, acetaminophen, and a gabapentinoid—is increasingly accepted as part of multimodal analgesia. The selective COX-2 inhibitor targets inflammatory prostaglandins and has anti-inflammatory and analgesic effects; acetaminophen, an effective analgesic with an unclear mechanism of action, can reduce postoperative opioid consumption¹² and works synergistically with NSAIDs¹³; and the gabapentinoid gabapentin has an analgesic effect likely contributing to decreased movement-related pain and subsequent improved functional recovery (data are mixed on whether continuing gabapentin after surgery prevents CPSP).¹⁴⁻¹⁶

Although serotonin and norepinephrine reuptake inhibitors (SNRIs) are commonly used in outpatient management of chronic pelvic pain, data suggest that their role in perioperative pain management is evolving. As SNRIs may reduce central nervous system (CNS) sensitization,¹⁷ their analgesic effect is thought to result from increased descending inhibitory tone in the CNS, which makes this class of medication ideal for patients with chronic neuropathic pain.¹⁵

Limited data also suggest a role for SNRIs in decreasing immediate postoperative pain and CPSP in high-risk patients. Studies of duloxetine use in the immediate perioperative period have found reduced postoperative acute pain and opioid use.^18,19 In addition, a short course of low-dose (37.5 mg) venlafaxine both before and after surgery has demonstrated a reduction in postoperative opioid use and a reduction in movement-related pain 6 months after surgery.²⁰

Intraoperative management

The surgical and anesthesia teams share the goal of optimizing both pain control and postoperative recovery. Surgical team members, who want longer-acting anesthetics for infiltration of incision sites, discuss with the anesthesiologist the appropriateness of using peripheral nerve blocks or neuraxial anesthesia, given the patient’s history and planned procedure. Anesthesia team members can improve anesthesia and minimize intraoperative opioid use through several methods, including total intravenous anesthesia,²¹ dexamethasone,²² ketorolac,²³ and intravenous ketamine. Ketamine, in particular, has a wide range of surgical applications and has been found to reduce postoperative pain, postoperative pain medication use, and the risk of CPSP.²

Incision sites should be infiltrated before and after surgery. Lidocaine traditionally is used for its rapid onset of action in reducing surgical site pain, but its short half-life may limit its applicability to postoperative pain. Recently, bupivacaine (half-life, 3.5 hours) and liposomal bupivacaine (24–34 hours) have gained more attention. Both of these medications appear to be as effective as lidocaine in reducing surgical site pain.²⁴

Transversus abdominis plane (TAP) blocks have been used as an adjunct in pain management during abdominopelvic surgery. Although initial data on postoperative pain and opioid use reductions with TAP blocks were inconclusive,²⁵ more recent data showed a role for TAP blocks in a multimodal approach for reducing opioid use during laparoscopic and open surgery.^26,27 Given the small number of studies on using liposomal bupivacaine for peripheral nerve blocks (eg, TAP blocks) in postoperative pain management, current data are inconclusive.²⁸

Postoperative management

The ERP approach calls for continuing multimodal analgesia after surgery—in most cases, scheduling early use of oral acetaminophen and ibuprofen, and providing short-acting, low-dose opioid analgesia as needed. All patients should be given a bowel regimen. Similar to undergoing prehabilitation for surgery, patients should prepare themselves for recovery. They should be encouraged to engage in early ambulation and oral intake and, when clinically appropriate, be given same-day discharge for minimally invasive surgical procedures.

Patients with chronic pain before surgery are at increased risk for suboptimal postoperative pain management, and those who are dependent on opioids require additional perioperative measures for adequate postoperative pain control. In these complicated cases, it is appropriate to enlist a pain specialist, potentially before surgery, to help plan perioperative and postoperative pain management.² Postoperative pain management for opioid-dependent patients should include pharmacologic and nonpharmacologic interventions, such as use of nonopioid medications (eg, gabapentin) and continuation of CBT. Patients with chronic pain should be closely followed up for assessment of postoperative pain control and recovery.

CASE Resolved

Surgical management is one aspect of the longer term multimodal pain management strategy for this patient. After preoperative pelvic floor physical therapy, she is receptive to starting a trial of an SNRI for her pain and mood symptoms. Both interventions allow for optimization of her preoperative physical and psychological status. Expectations are set that she will be discharged the day of surgery and that the surgery is but one component of her multimodal treatment plan. In addition, before surgery, she takes oral acetaminophen, gabapentin, and celecoxib—previously having had no contraindications to these medications. During surgery, bupivacaine is used for infiltration of all incision sites, and the anesthesia team administers ketamine and a TAP block. After surgery, the patient is prepared for same-day discharge and given the NSAIDs and acetaminophen she is scheduled to take over the next 72 hours. She is also given a limited prescription for oxycodone for breakthrough pain. An office visit 1 to 2 weeks after surgery is scheduled.

ERP strategies for surgical management of endometriosis have not only improved this patient’s postoperative recovery but also reduced her surgical stress response and subsequent transition to chronic postoperative pain. Many of the strategies used in this case are applicable to patients without chronic pain.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

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• Underdiagnosis and Undertreatment of Migraine
• A Framework for Understanding Burden of Disease
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Topics include:

• Underdiagnosis and Undertreatment of Migraine
• A Framework for Understanding Burden of Disease
• Burden and Cost
• New Insights in Migraine Pathophysiology

Click Here to Read Content.

Topics include:

• Underdiagnosis and Undertreatment of Migraine
• A Framework for Understanding Burden of Disease
• Burden and Cost
• New Insights in Migraine Pathophysiology

ORLANDO – E-cigarettes are likely safer than traditional cigarettes but it depends on the user, the voltage used, and the kind of liquid, according to a panel of experts at the joint congress of the American Academy of Allergy, Asthma and Immunology and the World Asthma Organization.

Thomas Casale, MD, professor of medicine at the University of South Florida, Tampa, said studies have found that in some ways, e-cigarettes seem safer. For example, the levels of carcinogens such as formaldehyde and heavy metals are found at levels that are 9-450 times higher in combustible cigarette smoke than e-cigarette vapor, he said. And toxic compounds have been found to be significantly lower in the urine of e-cigarette users compared to traditional cigarette smokers.

Thomas R. Collins/Frontline Medical News

But it’s not so simple. While e-cigarettes typically cause lower exposure to formaldehyde, when heated at a higher voltage, exposure to formaldehyde hemiacetal, a formaldehyde precursor, is about seven times higher for someone smoking 3 mL of e-cigarette fluid a day – similar to a pack a day – than the formaldehyde exposure of someone smoking the same quantity of combustible cigarettes.

Dr. Casale added that experienced e-cigarette users typically take longer puffs than traditional smokers and that the unregulated e-cigarette industry is rife with mislabeling on things such as how much nicotine is in a given fluid.

“It’s dependent upon the device, the battery, how much it heats up and what’s in the liquid,” he said. “So in general, are they safer? Probably. But not exactly.”

There are also no long-term data on e-cigarettes, he added.

The evidence on how e-cigarettes affects traditional smoking habits is also mixed.

Some studies have indicated that e-cigarettes use can be helpful in kicking a traditional cigarette habit, said Jill Poole, MD, of the University of Nebraska, Omaha.

A survey by the U.S. Census Bureau found that, in the 2014-2015 data collection year, about 60% of smokers of combustible cigarettes who also smoked e-cigarettes tried to quit smoking combustibles, compared to 40% of those who didn’t smoke e-cigarettes. And 8% of e-cigarette users were successful over 3 months, compared to 4% of nonusers.

Thomas R. Collins/ Frontline Medical News

But data reveals risks for kids who’ve never smoked and then start using e-cigarettes.

“Does noncigarette tobacco use among never smoking youth determine subsequent smoking initiation?” she said. “The answer is yes.”

Dr. Poole added that a study published this year found that youths who’d never smoked traditional cigarettes were 87% more likely to start if they had first tried e-cigarettes (JAMA Pediatr. 2018;172(2):181-187).

And more children are using e-cigarettes frequently. The National Youth Tobacco Survey found that 16% of high schoolers in 2016 had used e-cigarettes in the past 30 days, way up from 1.5% in 2011, even as traditional cigarette use has declined from 15.8% to 9.3% among those children over that time.

Thomas R. Collins/ Frontline Medical News

Loretta Que, MD, associate professor of medicine at Duke University, Durham, N.C., noted how advertising for e-cigarettes is similar to the old ads for traditional cigarettes, attempting to convey coolness. With their wide array of colors and thousands of flavors, there is no doubt that e-cigarette pens have caught on among children, she said.

“They’re becoming something akin to an iPhone case or a handbag.”

ORLANDO – E-cigarettes are likely safer than traditional cigarettes but it depends on the user, the voltage used, and the kind of liquid, according to a panel of experts at the joint congress of the American Academy of Allergy, Asthma and Immunology and the World Asthma Organization.

Thomas Casale, MD, professor of medicine at the University of South Florida, Tampa, said studies have found that in some ways, e-cigarettes seem safer. For example, the levels of carcinogens such as formaldehyde and heavy metals are found at levels that are 9-450 times higher in combustible cigarette smoke than e-cigarette vapor, he said. And toxic compounds have been found to be significantly lower in the urine of e-cigarette users compared to traditional cigarette smokers.

Thomas R. Collins/Frontline Medical News

But it’s not so simple. While e-cigarettes typically cause lower exposure to formaldehyde, when heated at a higher voltage, exposure to formaldehyde hemiacetal, a formaldehyde precursor, is about seven times higher for someone smoking 3 mL of e-cigarette fluid a day – similar to a pack a day – than the formaldehyde exposure of someone smoking the same quantity of combustible cigarettes.

Dr. Casale added that experienced e-cigarette users typically take longer puffs than traditional smokers and that the unregulated e-cigarette industry is rife with mislabeling on things such as how much nicotine is in a given fluid.

“It’s dependent upon the device, the battery, how much it heats up and what’s in the liquid,” he said. “So in general, are they safer? Probably. But not exactly.”

There are also no long-term data on e-cigarettes, he added.

The evidence on how e-cigarettes affects traditional smoking habits is also mixed.

Some studies have indicated that e-cigarettes use can be helpful in kicking a traditional cigarette habit, said Jill Poole, MD, of the University of Nebraska, Omaha.

A survey by the U.S. Census Bureau found that, in the 2014-2015 data collection year, about 60% of smokers of combustible cigarettes who also smoked e-cigarettes tried to quit smoking combustibles, compared to 40% of those who didn’t smoke e-cigarettes. And 8% of e-cigarette users were successful over 3 months, compared to 4% of nonusers.

Thomas R. Collins/ Frontline Medical News

But data reveals risks for kids who’ve never smoked and then start using e-cigarettes.

“Does noncigarette tobacco use among never smoking youth determine subsequent smoking initiation?” she said. “The answer is yes.”

Dr. Poole added that a study published this year found that youths who’d never smoked traditional cigarettes were 87% more likely to start if they had first tried e-cigarettes (JAMA Pediatr. 2018;172(2):181-187).

And more children are using e-cigarettes frequently. The National Youth Tobacco Survey found that 16% of high schoolers in 2016 had used e-cigarettes in the past 30 days, way up from 1.5% in 2011, even as traditional cigarette use has declined from 15.8% to 9.3% among those children over that time.

Thomas R. Collins/ Frontline Medical News

Loretta Que, MD, associate professor of medicine at Duke University, Durham, N.C., noted how advertising for e-cigarettes is similar to the old ads for traditional cigarettes, attempting to convey coolness. With their wide array of colors and thousands of flavors, there is no doubt that e-cigarette pens have caught on among children, she said.

“They’re becoming something akin to an iPhone case or a handbag.”

ORLANDO – E-cigarettes are likely safer than traditional cigarettes but it depends on the user, the voltage used, and the kind of liquid, according to a panel of experts at the joint congress of the American Academy of Allergy, Asthma and Immunology and the World Asthma Organization.

Thomas Casale, MD, professor of medicine at the University of South Florida, Tampa, said studies have found that in some ways, e-cigarettes seem safer. For example, the levels of carcinogens such as formaldehyde and heavy metals are found at levels that are 9-450 times higher in combustible cigarette smoke than e-cigarette vapor, he said. And toxic compounds have been found to be significantly lower in the urine of e-cigarette users compared to traditional cigarette smokers.

Thomas R. Collins/Frontline Medical News

But it’s not so simple. While e-cigarettes typically cause lower exposure to formaldehyde, when heated at a higher voltage, exposure to formaldehyde hemiacetal, a formaldehyde precursor, is about seven times higher for someone smoking 3 mL of e-cigarette fluid a day – similar to a pack a day – than the formaldehyde exposure of someone smoking the same quantity of combustible cigarettes.

Dr. Casale added that experienced e-cigarette users typically take longer puffs than traditional smokers and that the unregulated e-cigarette industry is rife with mislabeling on things such as how much nicotine is in a given fluid.

“It’s dependent upon the device, the battery, how much it heats up and what’s in the liquid,” he said. “So in general, are they safer? Probably. But not exactly.”

There are also no long-term data on e-cigarettes, he added.

The evidence on how e-cigarettes affects traditional smoking habits is also mixed.

Some studies have indicated that e-cigarettes use can be helpful in kicking a traditional cigarette habit, said Jill Poole, MD, of the University of Nebraska, Omaha.

A survey by the U.S. Census Bureau found that, in the 2014-2015 data collection year, about 60% of smokers of combustible cigarettes who also smoked e-cigarettes tried to quit smoking combustibles, compared to 40% of those who didn’t smoke e-cigarettes. And 8% of e-cigarette users were successful over 3 months, compared to 4% of nonusers.

Thomas R. Collins/ Frontline Medical News

But data reveals risks for kids who’ve never smoked and then start using e-cigarettes.

“Does noncigarette tobacco use among never smoking youth determine subsequent smoking initiation?” she said. “The answer is yes.”

Dr. Poole added that a study published this year found that youths who’d never smoked traditional cigarettes were 87% more likely to start if they had first tried e-cigarettes (JAMA Pediatr. 2018;172(2):181-187).

And more children are using e-cigarettes frequently. The National Youth Tobacco Survey found that 16% of high schoolers in 2016 had used e-cigarettes in the past 30 days, way up from 1.5% in 2011, even as traditional cigarette use has declined from 15.8% to 9.3% among those children over that time.

Thomas R. Collins/ Frontline Medical News

Loretta Que, MD, associate professor of medicine at Duke University, Durham, N.C., noted how advertising for e-cigarettes is similar to the old ads for traditional cigarettes, attempting to convey coolness. With their wide array of colors and thousands of flavors, there is no doubt that e-cigarette pens have caught on among children, she said.

“They’re becoming something akin to an iPhone case or a handbag.”

• Sepsis response team not beneficial
• Outcomes better for patients with H1N1 vaccination
• Lung recovery high after ECMO in near-fatal asthma
• Robotic-assisted pulmonary lobectomy removes large tumors
• Aspirin responsiveness improved in some with obstructive sleep apnea
• Solriamfetol improves excessive sleepiness in OSA patients
• Acute kidney injury linked with doubled inpatient VTEs
• Alarm reductions don’t improve ICU response times
• ARDS incidence is declining. Is it a preventable syndrome?
• Balanced crystalloids protect kidney better than saline
• Omalizumab helps asthma COPD overlap patients
• Nebulized glycopyrrolate improves lung function in COPD
• Nebulized LABA safe for long-term use in COPD
• IGRA preferred test for latent TB diagnosis
• Only half of appropriate COPD patients get long-acting bronchodilators
• Rapid influenza test obviates empiric antivirals
• Remimazolam surpasses midazolam
• Revised guidelines raise lung cancer screening age ceiling
• Ultrathin bronchoscopy plus radial EBUS unreliable at making diagnoses
• Phrenic-nerve stimulator maintains benefits for 18 months
• Cardiogenic shock boosts PAH readmissions 10-fold
• Evidence mounts for pulmonary embolism benefit from catheter thrombolysis
• Tracheobronchial tree size changes may predict IPF outcomes
• Shorter walk test predicts IPF outcomes
• Comparing arterial ratios may aid risk assessment in IPF
• FDA’s standards for approving generics are questioned
• Live Streaming at CHEST 2017

• Sepsis response team not beneficial
• Outcomes better for patients with H1N1 vaccination
• Lung recovery high after ECMO in near-fatal asthma
• Robotic-assisted pulmonary lobectomy removes large tumors
• Aspirin responsiveness improved in some with obstructive sleep apnea
• Solriamfetol improves excessive sleepiness in OSA patients
• Acute kidney injury linked with doubled inpatient VTEs
• Alarm reductions don’t improve ICU response times
• ARDS incidence is declining. Is it a preventable syndrome?
• Balanced crystalloids protect kidney better than saline
• Omalizumab helps asthma COPD overlap patients
• Nebulized glycopyrrolate improves lung function in COPD
• Nebulized LABA safe for long-term use in COPD
• IGRA preferred test for latent TB diagnosis
• Only half of appropriate COPD patients get long-acting bronchodilators
• Rapid influenza test obviates empiric antivirals
• Remimazolam surpasses midazolam
• Revised guidelines raise lung cancer screening age ceiling
• Ultrathin bronchoscopy plus radial EBUS unreliable at making diagnoses
• Phrenic-nerve stimulator maintains benefits for 18 months
• Cardiogenic shock boosts PAH readmissions 10-fold
• Evidence mounts for pulmonary embolism benefit from catheter thrombolysis
• Tracheobronchial tree size changes may predict IPF outcomes
• Shorter walk test predicts IPF outcomes
• Comparing arterial ratios may aid risk assessment in IPF
• FDA’s standards for approving generics are questioned
• Live Streaming at CHEST 2017

• Sepsis response team not beneficial
• Outcomes better for patients with H1N1 vaccination
• Lung recovery high after ECMO in near-fatal asthma
• Robotic-assisted pulmonary lobectomy removes large tumors
• Aspirin responsiveness improved in some with obstructive sleep apnea
• Solriamfetol improves excessive sleepiness in OSA patients
• Acute kidney injury linked with doubled inpatient VTEs
• Alarm reductions don’t improve ICU response times
• ARDS incidence is declining. Is it a preventable syndrome?
• Balanced crystalloids protect kidney better than saline
• Omalizumab helps asthma COPD overlap patients
• Nebulized glycopyrrolate improves lung function in COPD
• Nebulized LABA safe for long-term use in COPD
• IGRA preferred test for latent TB diagnosis
• Only half of appropriate COPD patients get long-acting bronchodilators
• Rapid influenza test obviates empiric antivirals
• Remimazolam surpasses midazolam
• Revised guidelines raise lung cancer screening age ceiling
• Ultrathin bronchoscopy plus radial EBUS unreliable at making diagnoses
• Phrenic-nerve stimulator maintains benefits for 18 months
• Cardiogenic shock boosts PAH readmissions 10-fold
• Evidence mounts for pulmonary embolism benefit from catheter thrombolysis
• Tracheobronchial tree size changes may predict IPF outcomes
• Shorter walk test predicts IPF outcomes
• Comparing arterial ratios may aid risk assessment in IPF
• FDA’s standards for approving generics are questioned
• Live Streaming at CHEST 2017

LAS VEGAS – The overlap of ADHD, conduct disorder, substance use disorder, and criminality likely reflect related underlying mechanisms, which may elucidate different developmental pathways of offending.

“Early interventions are key,” Praveen R. Kambam, MD, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.

According to Dr. Kambam, a clinical and forensic psychiatrist at the University of California, Los Angeles, ADHD is overrepresented in correctional settings worldwide, especially the hyperactive-impulsive subtype. “In juvenile settings, ADHD rates are 3-4 times higher than rates in the general population,” he said. “If you combine juvenile and adult prison populations worldwide, the rates are about 2-5 times higher than the general population.”

The risks are increased for comorbid oppositional defiant disorder (ODD) and conduct disorder. In fact, ADHD and conduct disorder co-occur in about 50% of cases. In girls, the prevalence rate of conduct disorder is steady at 0.8% around age 5 years and increases to 2.8% around age 15 years, while in boys, conduct disorder is steady at 2.1% around age 5 years and rises to 5.5% at age 15 years.

According to a literature review of 18 prospective studies, 13 retrospective studies, and four reviews, individuals with ADHD plus or minus conduct disorder had an increased the risk of antisocial personality disorder, and those with ADHD plus conduct disorder had an increased risk of criminality (J Atten Disord. 2016;20[10]:815-24). “So it’s a subtle difference, where antisocial personality disorder and criminality are slightly different,” Dr. Kambam said. “It could be that the diagnostic criteria are catching the same thing. However, the added [conduct disorder] suggests that there may be subpopulations that are vulnerable.”

He went on to note that individuals with ADHD and delinquency tend to have more learning problems, poor academic achievement, peer relationship problems, and risk of social rejection, while individuals with oppositional defiant disorder and delinquency tend to have peer relationship problems, a negative parent-child relationship, and increased risk of developing conduct disorder.

ADHD is associated with alcohol and drug use in adulthood and nicotine use in adolescence. “Comorbidity between ADHD and ODD/[conduct disorder] is robustly related to substance outcomes,” Dr. Kambam said. “However, both initiation and continuation of substance use disorder are more likely when ADHD symptoms are present, even when controlling for ODD/[conduct disorder]. As for substance use disorder [SUD] and delinquency, the onset of delinquency is more likely in children with onset of SUD by age 11, and SUDs are closely linked with criminality in both juveniles and adults.”

Comorbidity of SUD with conduct disorder and ADHD likely reflects multifactorial mechanisms, he said, such as inherent novelty seeking or school failure leading to association with antisocial peers. Risk factors for chronic offending include early onset of criminal behaviors, ADHD plus conduct disorder, and ODD. ADHD has an independent yet weaker relationship with antisocial behaviors as well, while ADHD, conduct disorder, and SUD are independently associated with increased recidivism.

Environmental factors for chronic offending include the home environment, peer response, parenting skills, and in utero exposures and perinatal complications. “Whether ADHD develops into more severe conduct problems depends considerably on exposure to potentiating environmental factors,” Dr. Kambam said. “The converse is also true: Low-risk environments promote desistance from this pathway in impulsive boys.” He added that the chronic offenders/criminality pathway likely stems from underlying mechanisms, such as impulsivity, low self-control, and executive dysfunction.

If left untreated, ADHD is associated with poor academic and employment outcomes, SUDs, depression, bipolar disorder, suicide attempts, vehicular accidents, and use of mental health services. “The economic costs are estimated to be $42.5 billion annually, so it has a large impact,” he said.

Limited evidence exists to support pharmacological treatments for conduct disorder, although stimulants/alpha-agonists, antipsychotics, lithium, and mood stabilizers may offer some benefit for target symptoms. “Most of the treatment data center around multisystemic therapy, including behavioral modification/parent management training, and functional family training,” Dr. Kambam said. “Treating disruptive behavior disorders and SUDs are 

likely to reduce criminality and recidivism, particularly if started early. There are many beneficial economic impacts. Think about the cost of having youth detained in the criminal justice systems. In Los Angeles County, that cost is about $230,000 per year per kid. That money can probably be better spent somewhere else.”

Numerous studies show that the nonmedical use of stimulants ranges from 25%-40%. “They’re mostly used to enhance academic and/or work performance, but some are used for euphoric effect,” he said. “Individuals in college and just out of college seem to be at the highest risk. There is a strong relationship between [conduct disorder]/[antisocial personality disorder] or SUDs and nonmedical use.”

Treatment with stimulants in correctional settings is controversial. “Some say try after failure of nonstimulants, while others say never use them due to substance abuse, misuse, intimidation of patients to surrender medication, and security/costs,” Dr. Kambam said. “The protocol for ADHD treatment in Massachusetts prisons calls for use of nonstimulants first, followed by ‘crushable’ stimulants if indicated.” The methylphenidate patch and lisdexamfetamine also can be effective in the incarcerated population.

Dr. Kambam reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SOURCE: Kambam PR. NPA 2018.

LAS VEGAS – The overlap of ADHD, conduct disorder, substance use disorder, and criminality likely reflect related underlying mechanisms, which may elucidate different developmental pathways of offending.

“Early interventions are key,” Praveen R. Kambam, MD, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.

According to Dr. Kambam, a clinical and forensic psychiatrist at the University of California, Los Angeles, ADHD is overrepresented in correctional settings worldwide, especially the hyperactive-impulsive subtype. “In juvenile settings, ADHD rates are 3-4 times higher than rates in the general population,” he said. “If you combine juvenile and adult prison populations worldwide, the rates are about 2-5 times higher than the general population.”

The risks are increased for comorbid oppositional defiant disorder (ODD) and conduct disorder. In fact, ADHD and conduct disorder co-occur in about 50% of cases. In girls, the prevalence rate of conduct disorder is steady at 0.8% around age 5 years and increases to 2.8% around age 15 years, while in boys, conduct disorder is steady at 2.1% around age 5 years and rises to 5.5% at age 15 years.

According to a literature review of 18 prospective studies, 13 retrospective studies, and four reviews, individuals with ADHD plus or minus conduct disorder had an increased the risk of antisocial personality disorder, and those with ADHD plus conduct disorder had an increased risk of criminality (J Atten Disord. 2016;20[10]:815-24). “So it’s a subtle difference, where antisocial personality disorder and criminality are slightly different,” Dr. Kambam said. “It could be that the diagnostic criteria are catching the same thing. However, the added [conduct disorder] suggests that there may be subpopulations that are vulnerable.”

He went on to note that individuals with ADHD and delinquency tend to have more learning problems, poor academic achievement, peer relationship problems, and risk of social rejection, while individuals with oppositional defiant disorder and delinquency tend to have peer relationship problems, a negative parent-child relationship, and increased risk of developing conduct disorder.

ADHD is associated with alcohol and drug use in adulthood and nicotine use in adolescence. “Comorbidity between ADHD and ODD/[conduct disorder] is robustly related to substance outcomes,” Dr. Kambam said. “However, both initiation and continuation of substance use disorder are more likely when ADHD symptoms are present, even when controlling for ODD/[conduct disorder]. As for substance use disorder [SUD] and delinquency, the onset of delinquency is more likely in children with onset of SUD by age 11, and SUDs are closely linked with criminality in both juveniles and adults.”

Comorbidity of SUD with conduct disorder and ADHD likely reflects multifactorial mechanisms, he said, such as inherent novelty seeking or school failure leading to association with antisocial peers. Risk factors for chronic offending include early onset of criminal behaviors, ADHD plus conduct disorder, and ODD. ADHD has an independent yet weaker relationship with antisocial behaviors as well, while ADHD, conduct disorder, and SUD are independently associated with increased recidivism.

Environmental factors for chronic offending include the home environment, peer response, parenting skills, and in utero exposures and perinatal complications. “Whether ADHD develops into more severe conduct problems depends considerably on exposure to potentiating environmental factors,” Dr. Kambam said. “The converse is also true: Low-risk environments promote desistance from this pathway in impulsive boys.” He added that the chronic offenders/criminality pathway likely stems from underlying mechanisms, such as impulsivity, low self-control, and executive dysfunction.

If left untreated, ADHD is associated with poor academic and employment outcomes, SUDs, depression, bipolar disorder, suicide attempts, vehicular accidents, and use of mental health services. “The economic costs are estimated to be $42.5 billion annually, so it has a large impact,” he said.

Limited evidence exists to support pharmacological treatments for conduct disorder, although stimulants/alpha-agonists, antipsychotics, lithium, and mood stabilizers may offer some benefit for target symptoms. “Most of the treatment data center around multisystemic therapy, including behavioral modification/parent management training, and functional family training,” Dr. Kambam said. “Treating disruptive behavior disorders and SUDs are 

likely to reduce criminality and recidivism, particularly if started early. There are many beneficial economic impacts. Think about the cost of having youth detained in the criminal justice systems. In Los Angeles County, that cost is about $230,000 per year per kid. That money can probably be better spent somewhere else.”

Numerous studies show that the nonmedical use of stimulants ranges from 25%-40%. “They’re mostly used to enhance academic and/or work performance, but some are used for euphoric effect,” he said. “Individuals in college and just out of college seem to be at the highest risk. There is a strong relationship between [conduct disorder]/[antisocial personality disorder] or SUDs and nonmedical use.”

Treatment with stimulants in correctional settings is controversial. “Some say try after failure of nonstimulants, while others say never use them due to substance abuse, misuse, intimidation of patients to surrender medication, and security/costs,” Dr. Kambam said. “The protocol for ADHD treatment in Massachusetts prisons calls for use of nonstimulants first, followed by ‘crushable’ stimulants if indicated.” The methylphenidate patch and lisdexamfetamine also can be effective in the incarcerated population.

Dr. Kambam reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SOURCE: Kambam PR. NPA 2018.

LAS VEGAS – The overlap of ADHD, conduct disorder, substance use disorder, and criminality likely reflect related underlying mechanisms, which may elucidate different developmental pathways of offending.

“Early interventions are key,” Praveen R. Kambam, MD, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.

According to Dr. Kambam, a clinical and forensic psychiatrist at the University of California, Los Angeles, ADHD is overrepresented in correctional settings worldwide, especially the hyperactive-impulsive subtype. “In juvenile settings, ADHD rates are 3-4 times higher than rates in the general population,” he said. “If you combine juvenile and adult prison populations worldwide, the rates are about 2-5 times higher than the general population.”

The risks are increased for comorbid oppositional defiant disorder (ODD) and conduct disorder. In fact, ADHD and conduct disorder co-occur in about 50% of cases. In girls, the prevalence rate of conduct disorder is steady at 0.8% around age 5 years and increases to 2.8% around age 15 years, while in boys, conduct disorder is steady at 2.1% around age 5 years and rises to 5.5% at age 15 years.

According to a literature review of 18 prospective studies, 13 retrospective studies, and four reviews, individuals with ADHD plus or minus conduct disorder had an increased the risk of antisocial personality disorder, and those with ADHD plus conduct disorder had an increased risk of criminality (J Atten Disord. 2016;20[10]:815-24). “So it’s a subtle difference, where antisocial personality disorder and criminality are slightly different,” Dr. Kambam said. “It could be that the diagnostic criteria are catching the same thing. However, the added [conduct disorder] suggests that there may be subpopulations that are vulnerable.”

He went on to note that individuals with ADHD and delinquency tend to have more learning problems, poor academic achievement, peer relationship problems, and risk of social rejection, while individuals with oppositional defiant disorder and delinquency tend to have peer relationship problems, a negative parent-child relationship, and increased risk of developing conduct disorder.

ADHD is associated with alcohol and drug use in adulthood and nicotine use in adolescence. “Comorbidity between ADHD and ODD/[conduct disorder] is robustly related to substance outcomes,” Dr. Kambam said. “However, both initiation and continuation of substance use disorder are more likely when ADHD symptoms are present, even when controlling for ODD/[conduct disorder]. As for substance use disorder [SUD] and delinquency, the onset of delinquency is more likely in children with onset of SUD by age 11, and SUDs are closely linked with criminality in both juveniles and adults.”

Comorbidity of SUD with conduct disorder and ADHD likely reflects multifactorial mechanisms, he said, such as inherent novelty seeking or school failure leading to association with antisocial peers. Risk factors for chronic offending include early onset of criminal behaviors, ADHD plus conduct disorder, and ODD. ADHD has an independent yet weaker relationship with antisocial behaviors as well, while ADHD, conduct disorder, and SUD are independently associated with increased recidivism.

Environmental factors for chronic offending include the home environment, peer response, parenting skills, and in utero exposures and perinatal complications. “Whether ADHD develops into more severe conduct problems depends considerably on exposure to potentiating environmental factors,” Dr. Kambam said. “The converse is also true: Low-risk environments promote desistance from this pathway in impulsive boys.” He added that the chronic offenders/criminality pathway likely stems from underlying mechanisms, such as impulsivity, low self-control, and executive dysfunction.

If left untreated, ADHD is associated with poor academic and employment outcomes, SUDs, depression, bipolar disorder, suicide attempts, vehicular accidents, and use of mental health services. “The economic costs are estimated to be $42.5 billion annually, so it has a large impact,” he said.

Limited evidence exists to support pharmacological treatments for conduct disorder, although stimulants/alpha-agonists, antipsychotics, lithium, and mood stabilizers may offer some benefit for target symptoms. “Most of the treatment data center around multisystemic therapy, including behavioral modification/parent management training, and functional family training,” Dr. Kambam said. “Treating disruptive behavior disorders and SUDs are 

likely to reduce criminality and recidivism, particularly if started early. There are many beneficial economic impacts. Think about the cost of having youth detained in the criminal justice systems. In Los Angeles County, that cost is about $230,000 per year per kid. That money can probably be better spent somewhere else.”

Numerous studies show that the nonmedical use of stimulants ranges from 25%-40%. “They’re mostly used to enhance academic and/or work performance, but some are used for euphoric effect,” he said. “Individuals in college and just out of college seem to be at the highest risk. There is a strong relationship between [conduct disorder]/[antisocial personality disorder] or SUDs and nonmedical use.”

Treatment with stimulants in correctional settings is controversial. “Some say try after failure of nonstimulants, while others say never use them due to substance abuse, misuse, intimidation of patients to surrender medication, and security/costs,” Dr. Kambam said. “The protocol for ADHD treatment in Massachusetts prisons calls for use of nonstimulants first, followed by ‘crushable’ stimulants if indicated.” The methylphenidate patch and lisdexamfetamine also can be effective in the incarcerated population.

Dr. Kambam reported having no financial disclosures.

dbrunk@frontlinemedcom.com

SOURCE: Kambam PR. NPA 2018.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

The immune checkpoint inhibitor avelumab (Bavencio), targeted against programmed cell death protein 1 and its ligand (PD1/PD-L1), appears to be well tolerated with a manageable safety profile, pooled data from two clinical trials suggest.

Of the 1,738 patients enrolled in the phase 1 JAVELIN solid tumor trial and the phase 2 JAVELIN Merkel 200 trial, 1,164 (67%) had a treatment-related adverse event (TRAE), and 177 (10.2%) had grade 3 or greater TRAEs. Grade 3 or greater immune-related adverse events (irAEs) occurred in just 2.2% of patients, reported Karen Kelly, MD, from the University of California, Davis, and her colleagues.

“Although conclusions drawn from cross-study comparisons should be made with caution, and to the best of our knowledge the number of pan-tumor clinical studies of [immune checkpoint inhibitor] monotherapy is limited, this analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of irAEs that is consistent with that of other ICIs,” they wrote in Cancer.

Adverse events common with other immune checkpoint inhibitors include low-grade fatigue, pruritus, and rash, as well as serious irAEs, including high-grade pneumonitis and autoimmune-like side effects, the authors noted.

To characterize the adverse event profile of avelumab, they reviewed safety data on 1,650 patients enrolled in the solid tumor trial and 88 enrolled in the Merkel cell carcinoma trial, which included all patients in the trial who had received at least one dose of avelumab monotherapy by the cutoff date.

At the time of the analysis, 287 patients (16.5%) were continuing treatment, and 1,451 had discontinued therapy, largely because of disease progression.

Nearly all patients – 1,697 (97.6%) – had at least one adverse event of any grade or cause.

Four patients died from what investigators determined were TRAEs, including autoimmune hepatitis with peritoneal metastases and ascites in a patient with gastric cancer, liver metastases and acute liver failure in a patient with metastatic breast cancer, respiratory distress in a patient with breast cancer and multiple comorbidities, and treatment-related pneumonitis with ongoing Clostridium difficile colitis and diverticulitis not related to study treatment in a patient with urothelial carcinoma.

An additional 59 patients (3.4%) died from adverse events not deemed to be treatment-related, and 104 patient (6%) died from unknown or undocumented causes.

Any grade of irAE occurred in 247 patients (14.2%) and were grade 3 or greater in 39 (2.2%). Management of irAEs included systemic corticosteroids and nonsteroidal immunosuppressants.

In all, 439 patients (25.3%) had infusion-related reactions, which were treated generally with systemic corticosteroid. The protocol of the solid tumor trial was amended later to include diphenhydramine and acetaminophen before the first avelumab infusion as prophylaxis.

The study was sponsored by Merck and part of an alliance between Merck and Pfizer. Dr. Kelly reported no conflicts of interest. Multiple coauthors reported research funding, consulting fees, honoraria, or other consideration from various companies, and several coauthors are Merck employees.

Variations in the clinical presentation of immunotherapy-induced inflammatory arthritis is partly explained by which treatment regimen was used to treat the cancer, a single-center study suggests.

While immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, their use for an ever-widening range of indications had created an increasing population of patients referred to rheumatologists for the management of immune-related adverse events (IrAEs), according to Laura C. Cappelli, MD, and her colleagues at John Hopkins University, Baltimore. 

Well-established guidelines exist for managing adverse events such as colitis and pneumonitis, but there are only preliminary guidelines for evaluating and treating immunotherapy-induced inflammatory arthritis (IA). “This may stem from a lack of consistent reporting of rheumatologic IrAEs in clinical trials, the non–life threatening nature of [inflammatory arthritis], or lack of recognition of musculoskeletal symptoms by treating providers,” they wrote in Seminars in Arthritis and Rheumatism.

Clinical trials have reported ranges of arthralgia in 1%-43% of patients treated with ICIs, but no accurate estimate of the incidence of IA exists. 

The researchers noted that treating patients with ICI-induced IA is complicated by a history of active or recently treated cancer and concerns over using immunosuppression in the context of ICI therapy. 

They set out to evaluate the clinical presentations of 30 patients seen in their clinic with ICI-induced IA. Patients were a median of 59 years old and 12 (40%) were female. Tumor types included metastatic melanoma, non–small cell lung cancer, small cell lung cancer, colorectal cancer, Hodgkin lymphoma, cutaneous lymphoma, renal cell carcinoma, duodenal carcinoma, Merkel cell carcinoma, cutaneous basal cell carcinoma, and cutaneous squamous cell carcinoma.

Sixteen patients were treated with anti–programmed cell death protein 1 (PD-1)/programmed death ligand 1 monotherapy, and 14 were treated with combination anti–CTLA-4/PD-1 therapy. 
Patients on combination therapy were significantly younger (7.5 years, P = 0.01) and were more likely to have metastatic melanoma as their underlying cancer.

Patients who received combination therapy were more likely to present first with knee IA (n = 10) and none had small joint involvement. In contrast, initial small joint involvement was more common in the monotherapy group (n = 6).

Most of the patients in the study had an additional IrAE, with colitis being the most common (n=10), followed by thyroid disease, pneumonitis, and rash. Patients on PD-1 or programmed death ligand 1 monotherapy were more likely to have IA as their first IrAE.

The research team noted that the median time to symptom onset was 5 months after ICI initiation.

Diagnosis of IA following patient-reported symptoms was an average of 5.2 months, with a significant difference in lag time to diagnosis depending on initial joint presentation. For example, patients with initial small joint involvement had a 10 month longer lag time to IA diagnosis than those with knees as the initial joint involved. 

In terms of treatment, 24 patients were treated with systemic corticosteroids and 10 required additional immunosuppression. The need for corticosteroids did not differ by ICI treatment regimen, but those treated with combination therapy were more likely to require additional immunosuppression (P = 0.02).

Tumor necrosis factor inhibitors with or without methotrexate were prescribed for seven patients. All of the patients had a clinical improvement in their arthritis symptoms. Four had a complete tumor response at the time of tumor necrosis factor inhibitor initiation with none having tumor progression.

The three patients treated with methotrexate monotherapy had a complete or sustained partial tumor response to ICI therapy and their cancer did not develop during IA management follow-up.  

The authors went on to look at the persistence of IA after cessation of therapy in a subset of 21 patients. They found that 18 of these patients still had IA symptoms months after stopping treatment. They suggested that the delay in diagnosis and treatment seen in their study might explain the finding. 

The study provides “critical information, not just for rheumatologists as they try to recognize subgroups in ICI-induced IA and diagnose patients with this new entity, but also for oncology providers who are usually first to encounter patients with ICI-induced IA and subsequently refer patients to rheumatology,” Dr. Cappelli and colleagues wrote.

The experience so far with using immunosuppression in ICI-induced IA “has been reassuring in terms of cancer outcomes, but more studies are needed to confirm this finding,” they concluded.

SOURCE: Cappelli LC et al. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit. 2018.02.011.

Variations in the clinical presentation of immunotherapy-induced inflammatory arthritis is partly explained by which treatment regimen was used to treat the cancer, a single-center study suggests.

While immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, their use for an ever-widening range of indications had created an increasing population of patients referred to rheumatologists for the management of immune-related adverse events (IrAEs), according to Laura C. Cappelli, MD, and her colleagues at John Hopkins University, Baltimore. 

Well-established guidelines exist for managing adverse events such as colitis and pneumonitis, but there are only preliminary guidelines for evaluating and treating immunotherapy-induced inflammatory arthritis (IA). “This may stem from a lack of consistent reporting of rheumatologic IrAEs in clinical trials, the non–life threatening nature of [inflammatory arthritis], or lack of recognition of musculoskeletal symptoms by treating providers,” they wrote in Seminars in Arthritis and Rheumatism.

Clinical trials have reported ranges of arthralgia in 1%-43% of patients treated with ICIs, but no accurate estimate of the incidence of IA exists. 

The researchers noted that treating patients with ICI-induced IA is complicated by a history of active or recently treated cancer and concerns over using immunosuppression in the context of ICI therapy. 

They set out to evaluate the clinical presentations of 30 patients seen in their clinic with ICI-induced IA. Patients were a median of 59 years old and 12 (40%) were female. Tumor types included metastatic melanoma, non–small cell lung cancer, small cell lung cancer, colorectal cancer, Hodgkin lymphoma, cutaneous lymphoma, renal cell carcinoma, duodenal carcinoma, Merkel cell carcinoma, cutaneous basal cell carcinoma, and cutaneous squamous cell carcinoma.

Sixteen patients were treated with anti–programmed cell death protein 1 (PD-1)/programmed death ligand 1 monotherapy, and 14 were treated with combination anti–CTLA-4/PD-1 therapy. 
Patients on combination therapy were significantly younger (7.5 years, P = 0.01) and were more likely to have metastatic melanoma as their underlying cancer.

Patients who received combination therapy were more likely to present first with knee IA (n = 10) and none had small joint involvement. In contrast, initial small joint involvement was more common in the monotherapy group (n = 6).

Most of the patients in the study had an additional IrAE, with colitis being the most common (n=10), followed by thyroid disease, pneumonitis, and rash. Patients on PD-1 or programmed death ligand 1 monotherapy were more likely to have IA as their first IrAE.

The research team noted that the median time to symptom onset was 5 months after ICI initiation.

Diagnosis of IA following patient-reported symptoms was an average of 5.2 months, with a significant difference in lag time to diagnosis depending on initial joint presentation. For example, patients with initial small joint involvement had a 10 month longer lag time to IA diagnosis than those with knees as the initial joint involved. 

In terms of treatment, 24 patients were treated with systemic corticosteroids and 10 required additional immunosuppression. The need for corticosteroids did not differ by ICI treatment regimen, but those treated with combination therapy were more likely to require additional immunosuppression (P = 0.02).

Tumor necrosis factor inhibitors with or without methotrexate were prescribed for seven patients. All of the patients had a clinical improvement in their arthritis symptoms. Four had a complete tumor response at the time of tumor necrosis factor inhibitor initiation with none having tumor progression.

The three patients treated with methotrexate monotherapy had a complete or sustained partial tumor response to ICI therapy and their cancer did not develop during IA management follow-up.  

The authors went on to look at the persistence of IA after cessation of therapy in a subset of 21 patients. They found that 18 of these patients still had IA symptoms months after stopping treatment. They suggested that the delay in diagnosis and treatment seen in their study might explain the finding. 

The study provides “critical information, not just for rheumatologists as they try to recognize subgroups in ICI-induced IA and diagnose patients with this new entity, but also for oncology providers who are usually first to encounter patients with ICI-induced IA and subsequently refer patients to rheumatology,” Dr. Cappelli and colleagues wrote.

The experience so far with using immunosuppression in ICI-induced IA “has been reassuring in terms of cancer outcomes, but more studies are needed to confirm this finding,” they concluded.

SOURCE: Cappelli LC et al. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit. 2018.02.011.

Variations in the clinical presentation of immunotherapy-induced inflammatory arthritis is partly explained by which treatment regimen was used to treat the cancer, a single-center study suggests.

While immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, their use for an ever-widening range of indications had created an increasing population of patients referred to rheumatologists for the management of immune-related adverse events (IrAEs), according to Laura C. Cappelli, MD, and her colleagues at John Hopkins University, Baltimore. 

Well-established guidelines exist for managing adverse events such as colitis and pneumonitis, but there are only preliminary guidelines for evaluating and treating immunotherapy-induced inflammatory arthritis (IA). “This may stem from a lack of consistent reporting of rheumatologic IrAEs in clinical trials, the non–life threatening nature of [inflammatory arthritis], or lack of recognition of musculoskeletal symptoms by treating providers,” they wrote in Seminars in Arthritis and Rheumatism.

Clinical trials have reported ranges of arthralgia in 1%-43% of patients treated with ICIs, but no accurate estimate of the incidence of IA exists. 

The researchers noted that treating patients with ICI-induced IA is complicated by a history of active or recently treated cancer and concerns over using immunosuppression in the context of ICI therapy. 

They set out to evaluate the clinical presentations of 30 patients seen in their clinic with ICI-induced IA. Patients were a median of 59 years old and 12 (40%) were female. Tumor types included metastatic melanoma, non–small cell lung cancer, small cell lung cancer, colorectal cancer, Hodgkin lymphoma, cutaneous lymphoma, renal cell carcinoma, duodenal carcinoma, Merkel cell carcinoma, cutaneous basal cell carcinoma, and cutaneous squamous cell carcinoma.

Sixteen patients were treated with anti–programmed cell death protein 1 (PD-1)/programmed death ligand 1 monotherapy, and 14 were treated with combination anti–CTLA-4/PD-1 therapy. 
Patients on combination therapy were significantly younger (7.5 years, P = 0.01) and were more likely to have metastatic melanoma as their underlying cancer.

Patients who received combination therapy were more likely to present first with knee IA (n = 10) and none had small joint involvement. In contrast, initial small joint involvement was more common in the monotherapy group (n = 6).

Most of the patients in the study had an additional IrAE, with colitis being the most common (n=10), followed by thyroid disease, pneumonitis, and rash. Patients on PD-1 or programmed death ligand 1 monotherapy were more likely to have IA as their first IrAE.

The research team noted that the median time to symptom onset was 5 months after ICI initiation.

Diagnosis of IA following patient-reported symptoms was an average of 5.2 months, with a significant difference in lag time to diagnosis depending on initial joint presentation. For example, patients with initial small joint involvement had a 10 month longer lag time to IA diagnosis than those with knees as the initial joint involved. 

In terms of treatment, 24 patients were treated with systemic corticosteroids and 10 required additional immunosuppression. The need for corticosteroids did not differ by ICI treatment regimen, but those treated with combination therapy were more likely to require additional immunosuppression (P = 0.02).

Tumor necrosis factor inhibitors with or without methotrexate were prescribed for seven patients. All of the patients had a clinical improvement in their arthritis symptoms. Four had a complete tumor response at the time of tumor necrosis factor inhibitor initiation with none having tumor progression.

The three patients treated with methotrexate monotherapy had a complete or sustained partial tumor response to ICI therapy and their cancer did not develop during IA management follow-up.  

The authors went on to look at the persistence of IA after cessation of therapy in a subset of 21 patients. They found that 18 of these patients still had IA symptoms months after stopping treatment. They suggested that the delay in diagnosis and treatment seen in their study might explain the finding. 

The study provides “critical information, not just for rheumatologists as they try to recognize subgroups in ICI-induced IA and diagnose patients with this new entity, but also for oncology providers who are usually first to encounter patients with ICI-induced IA and subsequently refer patients to rheumatology,” Dr. Cappelli and colleagues wrote.

The experience so far with using immunosuppression in ICI-induced IA “has been reassuring in terms of cancer outcomes, but more studies are needed to confirm this finding,” they concluded.

SOURCE: Cappelli LC et al. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit. 2018.02.011.