Pain

A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.

The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.

Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).

OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.

Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.

“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.

He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.

Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”

Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy

Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.

They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.

“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.

Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.

IVIG May Be a Potential Treatment

Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.

In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.

Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.

Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”

Whelan and Chu have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.

The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.

Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).

OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.

Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.

“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.

He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.

Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”

Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy

Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.

They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.

“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.

Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.

IVIG May Be a Potential Treatment

Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.

In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.

Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.

Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”

Whelan and Chu have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.

The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.

Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).

OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.

Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.

“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.

He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.

Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”

Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy

Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.

They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.

“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.

Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.

IVIG May Be a Potential Treatment

Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.

In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.

Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.

Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”

Whelan and Chu have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Among women who have a coincidental appendectomy during surgery for chronic pelvic pain or endometriosis, about 15% have appendiceal endometriosis confirmed by pathological examination, according to a study.

“In the women with appendiceal endometriosis, only 26% had an appendix that looked abnormal,” said Whitney T. Ross, MD, of the department of obstetrics and gynecology at Penn State Health, Hershey.

The results, presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons, indicate that “appendiceal endometriosis is common in women receiving surgery for chronic pelvic pain or endometriosis,” she said. “This study and multiple other studies have also demonstrated that coincidental appendectomy is safe.”

The long-term impact of coincidental appendectomy and its effect on quality of life are not known, however, which may make it difficult to weigh the costs and benefits of the procedure, Dr. Ross said. “It is important to talk to patients about this procedure and determine which approach is the right approach for your institution.”

The study of 609 coincidental appendectomies did not include patients with retrocecal appendices, which may confound the true rate of appendiceal endometriosis, commented Saifuddin T. Mama, MD, MPH, of Rowan University, Camden, N.J.

When the investigators started the study, they were not sure of the risks and benefits of the procedure in patients with retrocecal appendices. An anecdotal report from another research group suggests that outcomes with retrocecal appendices may not be significantly different. “But that is certainly an important question and one that we would like to address in a future prospective study,” Dr. Ross said.

Surgeons have debated the role of coincidental appendectomy during gynecologic surgery. Concerns about safety and questions about the prevalence of appendiceal pathology are reasons that coincidental appendectomy has not been more widely adopted. On the other hand, the procedure may benefit patients and aid diagnosis.

To evaluate the role of coincidental appendectomy in the surgical excision of endometriosis, Dr. Ross and colleagues analyzed data from consecutive coincidental appendectomies performed at one institution between 2013 and 2019. They identified cases in a prospectively maintained surgical database to assess safety and the prevalence of appendiceal pathology.

iStockphoto.com

The indication for surgery was chronic pelvic pain but no visualized endometriosis for 42 patients, stage I-II endometriosis for 388 patients, and stage III-IV endometriosis for 179 patients.

Surgeries included laparoscopic hysterectomy (77.5%), operative laparoscopy (19.9%), and laparoscopic trachelectomy (2.6%). Pathological analysis of the appendices identified endometriosis in 14.9%, malignancy in 0.7%, polyps in 0.5%, and appendicitis in 0.3%.

Among women with chronic pelvic pain but no visualized endometriosis, 2.4% had appendiceal endometriosis. Among those with stage I-II endometriosis, 7% had appendiceal endometriosis, and in patients with stage III-IV endometriosis, the rate of appendiceal endometriosis was 35.2%.

In about 6% of patients with appendiceal endometriosis, the appendix was the only site of pathologically confirmed endometriosis.

Compared with chronic pelvic pain, stage III-IV endometriosis was associated with a significantly increased risk of appendiceal endometriosis (odds ratio, 22.2). The likelihood of appendiceal endometriosis also increased when the appendix looked abnormal (odds ratio, 6.5).

The probability of diagnosing appendiceal endometriosis also increases with the number of other locations of confirmed endometriosis.

“Our surgical decision making is based off of intraoperative findings. However, the final gold-standard diagnosis can’t take place until the pathologic specimen is analyzed,” she said. “We also know that there is a significant discordance, as high as 50%, in early-stage endometriosis between visual inspection and pathology findings.”

There were no complications related to the performance of a coincidental appendectomy during surgery or in the 12 weeks after.

Dr. Ross outlined surgeons’ three main options for performing coincidental appendectomy in patients undergoing surgery for chronic pelvic pain or endometriosis: universal coincidental appendectomy, targeted appendectomy based on operative findings, and performing the procedure based on the appearance of the appendix.

Basing the decision on appearance “is going to miss a lot of appendiceal endometriosis,” Dr. Ross said. In the present study, 67 of the 91 cases, about 74%, would have been missed.

Dr. Ross and Dr. Mama had no relevant financial disclosures. The study coauthors disclosed ties to Titan Medical, Merck, and AbbVie.

jremaly@mdedge.com

SOURCE: Ross WT et al. SGS 2020, Abstract 14.

Among women who have a coincidental appendectomy during surgery for chronic pelvic pain or endometriosis, about 15% have appendiceal endometriosis confirmed by pathological examination, according to a study.

“In the women with appendiceal endometriosis, only 26% had an appendix that looked abnormal,” said Whitney T. Ross, MD, of the department of obstetrics and gynecology at Penn State Health, Hershey.

The results, presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons, indicate that “appendiceal endometriosis is common in women receiving surgery for chronic pelvic pain or endometriosis,” she said. “This study and multiple other studies have also demonstrated that coincidental appendectomy is safe.”

The long-term impact of coincidental appendectomy and its effect on quality of life are not known, however, which may make it difficult to weigh the costs and benefits of the procedure, Dr. Ross said. “It is important to talk to patients about this procedure and determine which approach is the right approach for your institution.”

The study of 609 coincidental appendectomies did not include patients with retrocecal appendices, which may confound the true rate of appendiceal endometriosis, commented Saifuddin T. Mama, MD, MPH, of Rowan University, Camden, N.J.

When the investigators started the study, they were not sure of the risks and benefits of the procedure in patients with retrocecal appendices. An anecdotal report from another research group suggests that outcomes with retrocecal appendices may not be significantly different. “But that is certainly an important question and one that we would like to address in a future prospective study,” Dr. Ross said.

Surgeons have debated the role of coincidental appendectomy during gynecologic surgery. Concerns about safety and questions about the prevalence of appendiceal pathology are reasons that coincidental appendectomy has not been more widely adopted. On the other hand, the procedure may benefit patients and aid diagnosis.

To evaluate the role of coincidental appendectomy in the surgical excision of endometriosis, Dr. Ross and colleagues analyzed data from consecutive coincidental appendectomies performed at one institution between 2013 and 2019. They identified cases in a prospectively maintained surgical database to assess safety and the prevalence of appendiceal pathology.

iStockphoto.com

The indication for surgery was chronic pelvic pain but no visualized endometriosis for 42 patients, stage I-II endometriosis for 388 patients, and stage III-IV endometriosis for 179 patients.

Surgeries included laparoscopic hysterectomy (77.5%), operative laparoscopy (19.9%), and laparoscopic trachelectomy (2.6%). Pathological analysis of the appendices identified endometriosis in 14.9%, malignancy in 0.7%, polyps in 0.5%, and appendicitis in 0.3%.

Among women with chronic pelvic pain but no visualized endometriosis, 2.4% had appendiceal endometriosis. Among those with stage I-II endometriosis, 7% had appendiceal endometriosis, and in patients with stage III-IV endometriosis, the rate of appendiceal endometriosis was 35.2%.

In about 6% of patients with appendiceal endometriosis, the appendix was the only site of pathologically confirmed endometriosis.

Compared with chronic pelvic pain, stage III-IV endometriosis was associated with a significantly increased risk of appendiceal endometriosis (odds ratio, 22.2). The likelihood of appendiceal endometriosis also increased when the appendix looked abnormal (odds ratio, 6.5).

The probability of diagnosing appendiceal endometriosis also increases with the number of other locations of confirmed endometriosis.

“Our surgical decision making is based off of intraoperative findings. However, the final gold-standard diagnosis can’t take place until the pathologic specimen is analyzed,” she said. “We also know that there is a significant discordance, as high as 50%, in early-stage endometriosis between visual inspection and pathology findings.”

There were no complications related to the performance of a coincidental appendectomy during surgery or in the 12 weeks after.

Dr. Ross outlined surgeons’ three main options for performing coincidental appendectomy in patients undergoing surgery for chronic pelvic pain or endometriosis: universal coincidental appendectomy, targeted appendectomy based on operative findings, and performing the procedure based on the appearance of the appendix.

Basing the decision on appearance “is going to miss a lot of appendiceal endometriosis,” Dr. Ross said. In the present study, 67 of the 91 cases, about 74%, would have been missed.

Dr. Ross and Dr. Mama had no relevant financial disclosures. The study coauthors disclosed ties to Titan Medical, Merck, and AbbVie.

jremaly@mdedge.com

SOURCE: Ross WT et al. SGS 2020, Abstract 14.

Among women who have a coincidental appendectomy during surgery for chronic pelvic pain or endometriosis, about 15% have appendiceal endometriosis confirmed by pathological examination, according to a study.

“In the women with appendiceal endometriosis, only 26% had an appendix that looked abnormal,” said Whitney T. Ross, MD, of the department of obstetrics and gynecology at Penn State Health, Hershey.

The results, presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons, indicate that “appendiceal endometriosis is common in women receiving surgery for chronic pelvic pain or endometriosis,” she said. “This study and multiple other studies have also demonstrated that coincidental appendectomy is safe.”

The long-term impact of coincidental appendectomy and its effect on quality of life are not known, however, which may make it difficult to weigh the costs and benefits of the procedure, Dr. Ross said. “It is important to talk to patients about this procedure and determine which approach is the right approach for your institution.”

The study of 609 coincidental appendectomies did not include patients with retrocecal appendices, which may confound the true rate of appendiceal endometriosis, commented Saifuddin T. Mama, MD, MPH, of Rowan University, Camden, N.J.

When the investigators started the study, they were not sure of the risks and benefits of the procedure in patients with retrocecal appendices. An anecdotal report from another research group suggests that outcomes with retrocecal appendices may not be significantly different. “But that is certainly an important question and one that we would like to address in a future prospective study,” Dr. Ross said.

Surgeons have debated the role of coincidental appendectomy during gynecologic surgery. Concerns about safety and questions about the prevalence of appendiceal pathology are reasons that coincidental appendectomy has not been more widely adopted. On the other hand, the procedure may benefit patients and aid diagnosis.

To evaluate the role of coincidental appendectomy in the surgical excision of endometriosis, Dr. Ross and colleagues analyzed data from consecutive coincidental appendectomies performed at one institution between 2013 and 2019. They identified cases in a prospectively maintained surgical database to assess safety and the prevalence of appendiceal pathology.

iStockphoto.com

The indication for surgery was chronic pelvic pain but no visualized endometriosis for 42 patients, stage I-II endometriosis for 388 patients, and stage III-IV endometriosis for 179 patients.

Surgeries included laparoscopic hysterectomy (77.5%), operative laparoscopy (19.9%), and laparoscopic trachelectomy (2.6%). Pathological analysis of the appendices identified endometriosis in 14.9%, malignancy in 0.7%, polyps in 0.5%, and appendicitis in 0.3%.

Among women with chronic pelvic pain but no visualized endometriosis, 2.4% had appendiceal endometriosis. Among those with stage I-II endometriosis, 7% had appendiceal endometriosis, and in patients with stage III-IV endometriosis, the rate of appendiceal endometriosis was 35.2%.

In about 6% of patients with appendiceal endometriosis, the appendix was the only site of pathologically confirmed endometriosis.

Compared with chronic pelvic pain, stage III-IV endometriosis was associated with a significantly increased risk of appendiceal endometriosis (odds ratio, 22.2). The likelihood of appendiceal endometriosis also increased when the appendix looked abnormal (odds ratio, 6.5).

The probability of diagnosing appendiceal endometriosis also increases with the number of other locations of confirmed endometriosis.

“Our surgical decision making is based off of intraoperative findings. However, the final gold-standard diagnosis can’t take place until the pathologic specimen is analyzed,” she said. “We also know that there is a significant discordance, as high as 50%, in early-stage endometriosis between visual inspection and pathology findings.”

There were no complications related to the performance of a coincidental appendectomy during surgery or in the 12 weeks after.

Dr. Ross outlined surgeons’ three main options for performing coincidental appendectomy in patients undergoing surgery for chronic pelvic pain or endometriosis: universal coincidental appendectomy, targeted appendectomy based on operative findings, and performing the procedure based on the appearance of the appendix.

Basing the decision on appearance “is going to miss a lot of appendiceal endometriosis,” Dr. Ross said. In the present study, 67 of the 91 cases, about 74%, would have been missed.

Dr. Ross and Dr. Mama had no relevant financial disclosures. The study coauthors disclosed ties to Titan Medical, Merck, and AbbVie.

jremaly@mdedge.com

SOURCE: Ross WT et al. SGS 2020, Abstract 14.

Evidence for a link between cannabis use and cardiovascular health remains unsupported, and the potential risks outweigh any potential benefits, according to a scientific statement from the American Heart Association.

American Heart Association

The increased legalization of cannabis and cannabis products in the United States has driven medical professionals to evaluate the safety and efficacy of cannabis in relation to health conditions, wrote Robert L. Page II, PharmD, of the University of Colorado, Aurora, and colleagues.

In a statement published in Circulation, the researchers noted that although cannabis has been shown to relieve pain and other symptoms in certain conditions, clinicians in the United States have been limited from studying its health effects because of federal law restrictions. “Cannabis remains a schedule I controlled substance, deeming no accepted medical use, a high potential for abuse, and an unacceptable safety profile,” the researchers wrote.

The statement addresses issues with the use of cannabis by individuals with cardiovascular disease or those at increased risk. Observational studies have shown no cardiovascular benefits associated with cannabis, the writers noted. The most common chemicals in cannabis include THC (tetrahydrocannabinolic acid) and CBD (cannabidiol).

Some research has shown associations between CBD cardiovascular features including lower blood pressure and reduced inflammation, the writers noted. However, THC, the component of cannabis associated with a “high” or intoxication, has been associated with heart rhythm abnormalities. The writers cited data suggesting an increased risk of heart attacks, atrial fibrillation and heart failure, although more research is needed.

The statement outlines common cannabis formulations including plant-based, extracts, crystalline forms, edible products, and tinctures. In addition, the statement notes that synthetic cannabis products are marketed and used in the United States without subject to regulation.

“Over the past 5 years, we have seen a surge in cannabis use, particularly during the COVID-19 pandemic here in Colorado, especially among adolescents and young adults,” Dr. Page said in an interview. Because of the surge, health care practitioners need to familiarize themselves with not only the benefits, but risks associated with cannabis use regardless of the formulation,” he said. As heart disease remains a leading cause of death in the United States, understanding the cardiovascular risks associated with cannabis is crucial at this time.

Dr. Page noted that popular attitudes about cannabis could pose risks to users’ cardiovascular health. “One leading misconception about cannabis is because it is ‘natural’ it must be safe,” Dr. Page said. “As with all medications, cannabis has side effects, some of which can be cardiovascular in nature,” he said. “Significant drug-drug interactions can occur as CBD and THC, both found in cannabis, inhibit CYP3A4, which metabolizes a large number of medications used to treat many cardiovascular conditions,” he noted.

“Unfortunately, much of the published data is observational in nature due to the federal restrictions on cannabis as a schedule I drug,” said Dr. Page. “Nonetheless, safety signals have emerged regarding cannabis use and adverse cardiovascular outcomes, including myocardial infarction, heart failure, and atrial fibrillation. Carefully designed prospective short- and long-term studies regarding cannabis use and cardiovascular safety are needed,” he emphasized.

Areas in particular need of additional research include the cardiovascular effects of cannabis in several vulnerable populations such as adolescents, older adults, pregnant women, transplant recipients, and those with underlying cardiovascular disease, said Dr. Page.

“Nonetheless, based on the safety signals described within this Clinical Science Statement, an open discussion regarding the risks of using cannabis needs to occur between patient and health care providers,” he said. “Furthermore, patients must be transparent regarding their cannabis use with their cardiologist and primary care provider. The cannabis story will continue to evolve and is a rapidly moving/changing target,” he said.

“Whether cannabis use is a definitive risk factor for cardiovascular disease as with tobacco use is still unknown, and both acute and long-term studies are desperately needed to address this issue,” he said.

Dr. Page had no relevant financial conflicts to disclose.

SOURCE: Page et al. Circulation. 2020 Aug 5. doi: 10.1161/CIR.0000000000000883.

Evidence for a link between cannabis use and cardiovascular health remains unsupported, and the potential risks outweigh any potential benefits, according to a scientific statement from the American Heart Association.

American Heart Association

The increased legalization of cannabis and cannabis products in the United States has driven medical professionals to evaluate the safety and efficacy of cannabis in relation to health conditions, wrote Robert L. Page II, PharmD, of the University of Colorado, Aurora, and colleagues.

In a statement published in Circulation, the researchers noted that although cannabis has been shown to relieve pain and other symptoms in certain conditions, clinicians in the United States have been limited from studying its health effects because of federal law restrictions. “Cannabis remains a schedule I controlled substance, deeming no accepted medical use, a high potential for abuse, and an unacceptable safety profile,” the researchers wrote.

The statement addresses issues with the use of cannabis by individuals with cardiovascular disease or those at increased risk. Observational studies have shown no cardiovascular benefits associated with cannabis, the writers noted. The most common chemicals in cannabis include THC (tetrahydrocannabinolic acid) and CBD (cannabidiol).

Some research has shown associations between CBD cardiovascular features including lower blood pressure and reduced inflammation, the writers noted. However, THC, the component of cannabis associated with a “high” or intoxication, has been associated with heart rhythm abnormalities. The writers cited data suggesting an increased risk of heart attacks, atrial fibrillation and heart failure, although more research is needed.

The statement outlines common cannabis formulations including plant-based, extracts, crystalline forms, edible products, and tinctures. In addition, the statement notes that synthetic cannabis products are marketed and used in the United States without subject to regulation.

“Over the past 5 years, we have seen a surge in cannabis use, particularly during the COVID-19 pandemic here in Colorado, especially among adolescents and young adults,” Dr. Page said in an interview. Because of the surge, health care practitioners need to familiarize themselves with not only the benefits, but risks associated with cannabis use regardless of the formulation,” he said. As heart disease remains a leading cause of death in the United States, understanding the cardiovascular risks associated with cannabis is crucial at this time.

Dr. Page noted that popular attitudes about cannabis could pose risks to users’ cardiovascular health. “One leading misconception about cannabis is because it is ‘natural’ it must be safe,” Dr. Page said. “As with all medications, cannabis has side effects, some of which can be cardiovascular in nature,” he said. “Significant drug-drug interactions can occur as CBD and THC, both found in cannabis, inhibit CYP3A4, which metabolizes a large number of medications used to treat many cardiovascular conditions,” he noted.

“Unfortunately, much of the published data is observational in nature due to the federal restrictions on cannabis as a schedule I drug,” said Dr. Page. “Nonetheless, safety signals have emerged regarding cannabis use and adverse cardiovascular outcomes, including myocardial infarction, heart failure, and atrial fibrillation. Carefully designed prospective short- and long-term studies regarding cannabis use and cardiovascular safety are needed,” he emphasized.

Areas in particular need of additional research include the cardiovascular effects of cannabis in several vulnerable populations such as adolescents, older adults, pregnant women, transplant recipients, and those with underlying cardiovascular disease, said Dr. Page.

“Nonetheless, based on the safety signals described within this Clinical Science Statement, an open discussion regarding the risks of using cannabis needs to occur between patient and health care providers,” he said. “Furthermore, patients must be transparent regarding their cannabis use with their cardiologist and primary care provider. The cannabis story will continue to evolve and is a rapidly moving/changing target,” he said.

“Whether cannabis use is a definitive risk factor for cardiovascular disease as with tobacco use is still unknown, and both acute and long-term studies are desperately needed to address this issue,” he said.

Dr. Page had no relevant financial conflicts to disclose.

SOURCE: Page et al. Circulation. 2020 Aug 5. doi: 10.1161/CIR.0000000000000883.

Evidence for a link between cannabis use and cardiovascular health remains unsupported, and the potential risks outweigh any potential benefits, according to a scientific statement from the American Heart Association.

American Heart Association

The increased legalization of cannabis and cannabis products in the United States has driven medical professionals to evaluate the safety and efficacy of cannabis in relation to health conditions, wrote Robert L. Page II, PharmD, of the University of Colorado, Aurora, and colleagues.

In a statement published in Circulation, the researchers noted that although cannabis has been shown to relieve pain and other symptoms in certain conditions, clinicians in the United States have been limited from studying its health effects because of federal law restrictions. “Cannabis remains a schedule I controlled substance, deeming no accepted medical use, a high potential for abuse, and an unacceptable safety profile,” the researchers wrote.

The statement addresses issues with the use of cannabis by individuals with cardiovascular disease or those at increased risk. Observational studies have shown no cardiovascular benefits associated with cannabis, the writers noted. The most common chemicals in cannabis include THC (tetrahydrocannabinolic acid) and CBD (cannabidiol).

Some research has shown associations between CBD cardiovascular features including lower blood pressure and reduced inflammation, the writers noted. However, THC, the component of cannabis associated with a “high” or intoxication, has been associated with heart rhythm abnormalities. The writers cited data suggesting an increased risk of heart attacks, atrial fibrillation and heart failure, although more research is needed.

The statement outlines common cannabis formulations including plant-based, extracts, crystalline forms, edible products, and tinctures. In addition, the statement notes that synthetic cannabis products are marketed and used in the United States without subject to regulation.

“Over the past 5 years, we have seen a surge in cannabis use, particularly during the COVID-19 pandemic here in Colorado, especially among adolescents and young adults,” Dr. Page said in an interview. Because of the surge, health care practitioners need to familiarize themselves with not only the benefits, but risks associated with cannabis use regardless of the formulation,” he said. As heart disease remains a leading cause of death in the United States, understanding the cardiovascular risks associated with cannabis is crucial at this time.

Dr. Page noted that popular attitudes about cannabis could pose risks to users’ cardiovascular health. “One leading misconception about cannabis is because it is ‘natural’ it must be safe,” Dr. Page said. “As with all medications, cannabis has side effects, some of which can be cardiovascular in nature,” he said. “Significant drug-drug interactions can occur as CBD and THC, both found in cannabis, inhibit CYP3A4, which metabolizes a large number of medications used to treat many cardiovascular conditions,” he noted.

“Unfortunately, much of the published data is observational in nature due to the federal restrictions on cannabis as a schedule I drug,” said Dr. Page. “Nonetheless, safety signals have emerged regarding cannabis use and adverse cardiovascular outcomes, including myocardial infarction, heart failure, and atrial fibrillation. Carefully designed prospective short- and long-term studies regarding cannabis use and cardiovascular safety are needed,” he emphasized.

Areas in particular need of additional research include the cardiovascular effects of cannabis in several vulnerable populations such as adolescents, older adults, pregnant women, transplant recipients, and those with underlying cardiovascular disease, said Dr. Page.

“Nonetheless, based on the safety signals described within this Clinical Science Statement, an open discussion regarding the risks of using cannabis needs to occur between patient and health care providers,” he said. “Furthermore, patients must be transparent regarding their cannabis use with their cardiologist and primary care provider. The cannabis story will continue to evolve and is a rapidly moving/changing target,” he said.

“Whether cannabis use is a definitive risk factor for cardiovascular disease as with tobacco use is still unknown, and both acute and long-term studies are desperately needed to address this issue,” he said.

Dr. Page had no relevant financial conflicts to disclose.

SOURCE: Page et al. Circulation. 2020 Aug 5. doi: 10.1161/CIR.0000000000000883.

Patients on antithrombotics after an acute MI will face a greater risk for bleeding and secondary cardiovascular (CV) events if they start taking any nonaspirin NSAID, confirms a large observational study.

Like other research before it, the new study suggests those risks will be much lower for some nonaspirin NSAIDs than others. But it may also challenge at least some conventional thinking about the safety of these drugs, and is based solely on a large cohort in South Korea, a group for which such NSAID data has been in short supply.

“It was intriguing that our study presented better safety profiles with celecoxib and meloxicam versus other subtypes of NSAIDs,” noted the report, published online July 27 in the Journal of the American College of Cardiology.

Most of the NSAIDs included in the analysis, “including naproxen, conferred a significantly higher risk for cardiovascular and bleeding events, compared with celecoxib and meloxicam,” wrote the authors, led by Dong Oh Kang, MD, Korea University Guro Hospital, Seoul, South Korea.

A main contribution of the study “is the thorough and comprehensive evaluation of the Korean population by use of the nationwide prescription claims database that reflects real-world clinical practice,” senior author Cheol Ung Choi, MD, PhD, of the same institution, said in an interview.

“Because we included the largest number of patients of any comparable clinical studies on NSAID treatment after MI thus far, our study may allow the generalizability of the adverse events of NSAIDs to all patients by constituting global evidence encompassing different population groups,” Dr. Choi said.

The analysis has limitations along with its strengths, the authors acknowledged, including its observational design and potential for confounding not addressed in statistical adjustments.

Observers of the study concurred, but some cited evidence pointing to such confounding that is serious enough to question the entire study’s validity.

Among the cohort of more than 100,000 patients followed for an average of about 2.3 years after their MI, the adjusted risk of thromboembolic CV events went up almost 7 times for those who took any NSAID for at least 4 consecutive weeks, compared with those who didn’t take NSAIDs, based on prescription records.

Their adjusted risk of bleeding events – which included gastrointestinal, intracranial, respiratory, or urinary tract bleeding or posthemorrhagic anemia, the group writes – was increased 300%.

There was wide variance in the adjusted hazard ratios for outcomes by type of NSAID. The risk of CV events climbed from a low of about 3 with meloxicam and almost 5 for celecoxib to more than 10 and 12 for naproxen and dexibuprofen, respectively.

The hazard ratios for bleeding ranged from about 3 for both meloxicam and celecoxib to more than 6 for naproxen.

Of note, celecoxib and meloxicam both preferentially target the cyclooxygenase type 2 (COX-2) pathway, and naproxen among NSAIDs once had a reputation for relative cardiac safety, although subsequent studies have challenged that notion.

“On the basis of the contemporary guidelines, NSAID treatment should be limited as much as possible after MI; however, our data suggest that celecoxib and meloxicam could be considered possible alternative choices in patients with MI when NSAID prescription is unavoidable,” the group wrote.

They acknowledged some limitations of the analysis, including an observational design and the possibility of unidentified confounders; that mortality outcomes were not available from the National Health Insurance Service database used in the study; and that the 2009-2013 span for the data didn’t allow consideration of more contemporary antiplatelet agents and direct oral anticoagulants.

Also, NSAID use was based on prescriptions without regard to over-the-counter usage. Although use of over-the-counter NSAIDs is common in Korea, “most MI patients in Korea are prescribed most medications, including NSAIDs, in the hospital. So I think that usage of over-the-counter NSAIDs did not change the results,” Dr. Choi said.

“This study breaks new ground by demonstrating cardiovascular safety of meloxicam (and not only of celecoxib), probably because of its higher COX-2 selectivity,” wrote the authors of an accompanying editorial, Juan J. Badimon, PhD, and Carlos G. Santos-Gallego, MD, both of the Icahn School of Medicine at Mount Sinai, New York.

Notably, “this paper rejects the cardiovascular safety of naproxen, which had been suggested classically and in the previous Danish data, but that was not evident in this study.” The finding is consistent with the PRECISION trial, in which both bleeding and CV risk were increased with naproxen versus other NSAIDs, observed Dr. Badimon and Dr. Santos-Gallego.

They agreed with the authors in recommending that, “although NSAID treatment should be avoided in patients with MI, if the use of NSAIDs is inevitable due to comorbidities, the prescription of celecoxib and meloxicam could be considered as alternative options.”

But, “as no study is perfect, this article also presents some limitations,” the editorial agreed, citing some of the same issues noted by Dr. Kang and associates, along with potential confounding by indication and the lack of “clinical information to adjust (e.g., angiographic features, left ventricular function).”

“There’s undoubtedly residual confounding,” James M. Brophy, MD, PhD, a pharmacoepidemiologist at McGill University, Montreal, said in an interview.

The 400%-900% relative risks for CV events “are just too far in left field, compared to everything else we know,” he said. “There has never been a class of drugs that have shown this sort of magnitude of effect for adverse events.”

Even in PRECISION with its more than 24,000 high-coronary-risk patients randomized and followed for 5 years, Dr. Brophy observed, relative risks for the different NSAIDs varied by an order of magnitude of only 1-2.

“You should be interpreting things in the context of what is already known,” Dr. Brophy said. “The only conclusion I would draw is the paper is fatally flawed.”

The registry included 108,232 primarily male patients followed from their first diagnosed MI for CV and bleeding events. About 1.9% were prescribed at least one NSAID for 4 or more consecutive weeks during the follow-up period averaging 2.3 years, the group reported.

The most frequently prescribed NSAID was diclofenac, at about 72% of prescribed NSAIDs in the analysis for CV events and about 69% in the bleeding-event analysis.

Adding any NSAID to post-MI antithrombotic therapy led to an adjusted HR of 6.96 (P < .001) for CV events and 4.08 (P < .001) for bleeding events, compared with no NSAID treatment.

The 88% of the cohort who were on dual-antiplatelet therapy with aspirin and clopidogrel showed very nearly the same risk increases for both endpoints.

Further studies are needed to confirm the results “and ensure their generalizability to other populations,” Dr. Choi said. They should be validated especially using the claims data bases of countries near Korea, “such as Japan and Taiwan, to examine the reproducibility of the results in similar ethnic populations.”

That the study focused on a cohort in Korea is a strength, contended the authors as well as Dr. Badimon and Dr. Santos-Gallego, given “that most data about NSAIDs were extracted from Western populations, but the risk of thrombosis/bleeding post-MI varies according to ethnicity,” according to the editorial

Dr. Brophy agreed, but doubted that ethnic differences are responsible for variation in relative risks between the current results and other studies. “There are pharmacogenomic differences between different ethnicities as to how they activate these drugs. But I suspect that sort of difference is really minor. Maybe it leads to a 2% or a 5% difference in risks.”

Dr. Kang and associates, Dr. Badimon, Dr. Santos-Gallego, and Dr. Brophy disclosed no relevant financial relationships.

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

Patients on antithrombotics after an acute MI will face a greater risk for bleeding and secondary cardiovascular (CV) events if they start taking any nonaspirin NSAID, confirms a large observational study.

Like other research before it, the new study suggests those risks will be much lower for some nonaspirin NSAIDs than others. But it may also challenge at least some conventional thinking about the safety of these drugs, and is based solely on a large cohort in South Korea, a group for which such NSAID data has been in short supply.

“It was intriguing that our study presented better safety profiles with celecoxib and meloxicam versus other subtypes of NSAIDs,” noted the report, published online July 27 in the Journal of the American College of Cardiology.

Most of the NSAIDs included in the analysis, “including naproxen, conferred a significantly higher risk for cardiovascular and bleeding events, compared with celecoxib and meloxicam,” wrote the authors, led by Dong Oh Kang, MD, Korea University Guro Hospital, Seoul, South Korea.

A main contribution of the study “is the thorough and comprehensive evaluation of the Korean population by use of the nationwide prescription claims database that reflects real-world clinical practice,” senior author Cheol Ung Choi, MD, PhD, of the same institution, said in an interview.

“Because we included the largest number of patients of any comparable clinical studies on NSAID treatment after MI thus far, our study may allow the generalizability of the adverse events of NSAIDs to all patients by constituting global evidence encompassing different population groups,” Dr. Choi said.

The analysis has limitations along with its strengths, the authors acknowledged, including its observational design and potential for confounding not addressed in statistical adjustments.

Observers of the study concurred, but some cited evidence pointing to such confounding that is serious enough to question the entire study’s validity.

Among the cohort of more than 100,000 patients followed for an average of about 2.3 years after their MI, the adjusted risk of thromboembolic CV events went up almost 7 times for those who took any NSAID for at least 4 consecutive weeks, compared with those who didn’t take NSAIDs, based on prescription records.

Their adjusted risk of bleeding events – which included gastrointestinal, intracranial, respiratory, or urinary tract bleeding or posthemorrhagic anemia, the group writes – was increased 300%.

There was wide variance in the adjusted hazard ratios for outcomes by type of NSAID. The risk of CV events climbed from a low of about 3 with meloxicam and almost 5 for celecoxib to more than 10 and 12 for naproxen and dexibuprofen, respectively.

The hazard ratios for bleeding ranged from about 3 for both meloxicam and celecoxib to more than 6 for naproxen.

Of note, celecoxib and meloxicam both preferentially target the cyclooxygenase type 2 (COX-2) pathway, and naproxen among NSAIDs once had a reputation for relative cardiac safety, although subsequent studies have challenged that notion.

“On the basis of the contemporary guidelines, NSAID treatment should be limited as much as possible after MI; however, our data suggest that celecoxib and meloxicam could be considered possible alternative choices in patients with MI when NSAID prescription is unavoidable,” the group wrote.

They acknowledged some limitations of the analysis, including an observational design and the possibility of unidentified confounders; that mortality outcomes were not available from the National Health Insurance Service database used in the study; and that the 2009-2013 span for the data didn’t allow consideration of more contemporary antiplatelet agents and direct oral anticoagulants.

Also, NSAID use was based on prescriptions without regard to over-the-counter usage. Although use of over-the-counter NSAIDs is common in Korea, “most MI patients in Korea are prescribed most medications, including NSAIDs, in the hospital. So I think that usage of over-the-counter NSAIDs did not change the results,” Dr. Choi said.

“This study breaks new ground by demonstrating cardiovascular safety of meloxicam (and not only of celecoxib), probably because of its higher COX-2 selectivity,” wrote the authors of an accompanying editorial, Juan J. Badimon, PhD, and Carlos G. Santos-Gallego, MD, both of the Icahn School of Medicine at Mount Sinai, New York.

Notably, “this paper rejects the cardiovascular safety of naproxen, which had been suggested classically and in the previous Danish data, but that was not evident in this study.” The finding is consistent with the PRECISION trial, in which both bleeding and CV risk were increased with naproxen versus other NSAIDs, observed Dr. Badimon and Dr. Santos-Gallego.

They agreed with the authors in recommending that, “although NSAID treatment should be avoided in patients with MI, if the use of NSAIDs is inevitable due to comorbidities, the prescription of celecoxib and meloxicam could be considered as alternative options.”

But, “as no study is perfect, this article also presents some limitations,” the editorial agreed, citing some of the same issues noted by Dr. Kang and associates, along with potential confounding by indication and the lack of “clinical information to adjust (e.g., angiographic features, left ventricular function).”

“There’s undoubtedly residual confounding,” James M. Brophy, MD, PhD, a pharmacoepidemiologist at McGill University, Montreal, said in an interview.

The 400%-900% relative risks for CV events “are just too far in left field, compared to everything else we know,” he said. “There has never been a class of drugs that have shown this sort of magnitude of effect for adverse events.”

Even in PRECISION with its more than 24,000 high-coronary-risk patients randomized and followed for 5 years, Dr. Brophy observed, relative risks for the different NSAIDs varied by an order of magnitude of only 1-2.

“You should be interpreting things in the context of what is already known,” Dr. Brophy said. “The only conclusion I would draw is the paper is fatally flawed.”

The registry included 108,232 primarily male patients followed from their first diagnosed MI for CV and bleeding events. About 1.9% were prescribed at least one NSAID for 4 or more consecutive weeks during the follow-up period averaging 2.3 years, the group reported.

The most frequently prescribed NSAID was diclofenac, at about 72% of prescribed NSAIDs in the analysis for CV events and about 69% in the bleeding-event analysis.

Adding any NSAID to post-MI antithrombotic therapy led to an adjusted HR of 6.96 (P < .001) for CV events and 4.08 (P < .001) for bleeding events, compared with no NSAID treatment.

The 88% of the cohort who were on dual-antiplatelet therapy with aspirin and clopidogrel showed very nearly the same risk increases for both endpoints.

Further studies are needed to confirm the results “and ensure their generalizability to other populations,” Dr. Choi said. They should be validated especially using the claims data bases of countries near Korea, “such as Japan and Taiwan, to examine the reproducibility of the results in similar ethnic populations.”

That the study focused on a cohort in Korea is a strength, contended the authors as well as Dr. Badimon and Dr. Santos-Gallego, given “that most data about NSAIDs were extracted from Western populations, but the risk of thrombosis/bleeding post-MI varies according to ethnicity,” according to the editorial

Dr. Brophy agreed, but doubted that ethnic differences are responsible for variation in relative risks between the current results and other studies. “There are pharmacogenomic differences between different ethnicities as to how they activate these drugs. But I suspect that sort of difference is really minor. Maybe it leads to a 2% or a 5% difference in risks.”

Dr. Kang and associates, Dr. Badimon, Dr. Santos-Gallego, and Dr. Brophy disclosed no relevant financial relationships.

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

Patients on antithrombotics after an acute MI will face a greater risk for bleeding and secondary cardiovascular (CV) events if they start taking any nonaspirin NSAID, confirms a large observational study.

Like other research before it, the new study suggests those risks will be much lower for some nonaspirin NSAIDs than others. But it may also challenge at least some conventional thinking about the safety of these drugs, and is based solely on a large cohort in South Korea, a group for which such NSAID data has been in short supply.

“It was intriguing that our study presented better safety profiles with celecoxib and meloxicam versus other subtypes of NSAIDs,” noted the report, published online July 27 in the Journal of the American College of Cardiology.

Most of the NSAIDs included in the analysis, “including naproxen, conferred a significantly higher risk for cardiovascular and bleeding events, compared with celecoxib and meloxicam,” wrote the authors, led by Dong Oh Kang, MD, Korea University Guro Hospital, Seoul, South Korea.

A main contribution of the study “is the thorough and comprehensive evaluation of the Korean population by use of the nationwide prescription claims database that reflects real-world clinical practice,” senior author Cheol Ung Choi, MD, PhD, of the same institution, said in an interview.

“Because we included the largest number of patients of any comparable clinical studies on NSAID treatment after MI thus far, our study may allow the generalizability of the adverse events of NSAIDs to all patients by constituting global evidence encompassing different population groups,” Dr. Choi said.

The analysis has limitations along with its strengths, the authors acknowledged, including its observational design and potential for confounding not addressed in statistical adjustments.

Observers of the study concurred, but some cited evidence pointing to such confounding that is serious enough to question the entire study’s validity.

Among the cohort of more than 100,000 patients followed for an average of about 2.3 years after their MI, the adjusted risk of thromboembolic CV events went up almost 7 times for those who took any NSAID for at least 4 consecutive weeks, compared with those who didn’t take NSAIDs, based on prescription records.

Their adjusted risk of bleeding events – which included gastrointestinal, intracranial, respiratory, or urinary tract bleeding or posthemorrhagic anemia, the group writes – was increased 300%.

There was wide variance in the adjusted hazard ratios for outcomes by type of NSAID. The risk of CV events climbed from a low of about 3 with meloxicam and almost 5 for celecoxib to more than 10 and 12 for naproxen and dexibuprofen, respectively.

The hazard ratios for bleeding ranged from about 3 for both meloxicam and celecoxib to more than 6 for naproxen.

Of note, celecoxib and meloxicam both preferentially target the cyclooxygenase type 2 (COX-2) pathway, and naproxen among NSAIDs once had a reputation for relative cardiac safety, although subsequent studies have challenged that notion.

“On the basis of the contemporary guidelines, NSAID treatment should be limited as much as possible after MI; however, our data suggest that celecoxib and meloxicam could be considered possible alternative choices in patients with MI when NSAID prescription is unavoidable,” the group wrote.

They acknowledged some limitations of the analysis, including an observational design and the possibility of unidentified confounders; that mortality outcomes were not available from the National Health Insurance Service database used in the study; and that the 2009-2013 span for the data didn’t allow consideration of more contemporary antiplatelet agents and direct oral anticoagulants.

Also, NSAID use was based on prescriptions without regard to over-the-counter usage. Although use of over-the-counter NSAIDs is common in Korea, “most MI patients in Korea are prescribed most medications, including NSAIDs, in the hospital. So I think that usage of over-the-counter NSAIDs did not change the results,” Dr. Choi said.

“This study breaks new ground by demonstrating cardiovascular safety of meloxicam (and not only of celecoxib), probably because of its higher COX-2 selectivity,” wrote the authors of an accompanying editorial, Juan J. Badimon, PhD, and Carlos G. Santos-Gallego, MD, both of the Icahn School of Medicine at Mount Sinai, New York.

Notably, “this paper rejects the cardiovascular safety of naproxen, which had been suggested classically and in the previous Danish data, but that was not evident in this study.” The finding is consistent with the PRECISION trial, in which both bleeding and CV risk were increased with naproxen versus other NSAIDs, observed Dr. Badimon and Dr. Santos-Gallego.

They agreed with the authors in recommending that, “although NSAID treatment should be avoided in patients with MI, if the use of NSAIDs is inevitable due to comorbidities, the prescription of celecoxib and meloxicam could be considered as alternative options.”

But, “as no study is perfect, this article also presents some limitations,” the editorial agreed, citing some of the same issues noted by Dr. Kang and associates, along with potential confounding by indication and the lack of “clinical information to adjust (e.g., angiographic features, left ventricular function).”

“There’s undoubtedly residual confounding,” James M. Brophy, MD, PhD, a pharmacoepidemiologist at McGill University, Montreal, said in an interview.

The 400%-900% relative risks for CV events “are just too far in left field, compared to everything else we know,” he said. “There has never been a class of drugs that have shown this sort of magnitude of effect for adverse events.”

Even in PRECISION with its more than 24,000 high-coronary-risk patients randomized and followed for 5 years, Dr. Brophy observed, relative risks for the different NSAIDs varied by an order of magnitude of only 1-2.

“You should be interpreting things in the context of what is already known,” Dr. Brophy said. “The only conclusion I would draw is the paper is fatally flawed.”

The registry included 108,232 primarily male patients followed from their first diagnosed MI for CV and bleeding events. About 1.9% were prescribed at least one NSAID for 4 or more consecutive weeks during the follow-up period averaging 2.3 years, the group reported.

The most frequently prescribed NSAID was diclofenac, at about 72% of prescribed NSAIDs in the analysis for CV events and about 69% in the bleeding-event analysis.

Adding any NSAID to post-MI antithrombotic therapy led to an adjusted HR of 6.96 (P < .001) for CV events and 4.08 (P < .001) for bleeding events, compared with no NSAID treatment.

The 88% of the cohort who were on dual-antiplatelet therapy with aspirin and clopidogrel showed very nearly the same risk increases for both endpoints.

Further studies are needed to confirm the results “and ensure their generalizability to other populations,” Dr. Choi said. They should be validated especially using the claims data bases of countries near Korea, “such as Japan and Taiwan, to examine the reproducibility of the results in similar ethnic populations.”

That the study focused on a cohort in Korea is a strength, contended the authors as well as Dr. Badimon and Dr. Santos-Gallego, given “that most data about NSAIDs were extracted from Western populations, but the risk of thrombosis/bleeding post-MI varies according to ethnicity,” according to the editorial

Dr. Brophy agreed, but doubted that ethnic differences are responsible for variation in relative risks between the current results and other studies. “There are pharmacogenomic differences between different ethnicities as to how they activate these drugs. But I suspect that sort of difference is really minor. Maybe it leads to a 2% or a 5% difference in risks.”

Dr. Kang and associates, Dr. Badimon, Dr. Santos-Gallego, and Dr. Brophy disclosed no relevant financial relationships.

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

Older Americans – people aged 65 or older – make up 15% of the U.S. population, according to the Census Bureau. By the end of this decade, or the year 2030, this proportion will increase to 21% – and all “baby boomers,” those born between 1946 and 1964, will be older than 65.¹ Those demographic developments are occurring alongside a change in societal, legal, and public attitudes on cannabis.

VladK213/Getty Images

Liberalization of cannabis laws across the United States allows for ever easier access to medicinal and recreational cannabis. Traditionally, cannabis use, its effects, and related considerations in the adolescent and young adult populations have commanded significant research attention. Cannabis use in older adults, however, is not as well studied.² An exploration of trends in cannabis use by older adults and potential impact in terms of health is timely and important.

According to data from the National Survey on Drug Use and Health, cannabis use in adults aged 65 years and older appears to have been increasing steadily over the past 2 decades. Use among this group rose from 0.4% in 2006 and 2007, to 2.9% in 2015 and 2016.² And, most recently, use climbed from 3.7% in 2017 to 4.2% in 2018.²

Cannabis use also has risen among other adults. For those aged 50-64, cannabis use increased from 2.8% in 2006-2007 to 4.8% in 2012-2013.^2,3 Meanwhile, from 2015 to 2016, that number increased to 9.0%.^3,4

Past-year cannabis use in the groups of those aged 50-64 and those aged 65 and older appears to be higher in individuals with mental health problems, alcohol use disorder, and nicotine dependence.^5,6 Being male and being unmarried appear to be correlated with past-year cannabis use. Multimorbidity does not appear to be associated with past-year cannabis use. Those using cannabis tend to be long-term users and have first use at a much younger age, typically before age 21. Most older adults who report cannabis use do not perceive use to be of any risk or deem it only a slight risk.

Older adults use cannabis for both recreational and perceived medical benefits. Arthritis, chronic back pain, anxiety, depression, relaxation, stress reduction, and enhancement in terms of creativity are all purported reasons for use. However, there is limited to no evidence for the efficacy of cannabis in helping with those conditions and purposes. Clinical trials have shown that cannabis can be beneficial in managing pain and nausea, but those trials have not been conducted in older adults.^7,8

There is a real risk of cannabis use having a negative impact on the health of older adults. To begin with, the cannabis consumed today is significantly higher in potency than the cannabis that baby boomers were introduced to in their youth. The higher potency, combined with an age-related decline in function experienced by some older adults, makes them vulnerable to its known side effects, such as anxiety, dry mouth, tachycardia, high blood pressure, palpitations, wheezing, confusion, and dizziness.

Cannabis use is reported to bring a fourfold increase in cardiac events within the first hour of ingestion.⁹ Cognitive decline and memory impairment are well known adverse effects of cannabis use. Research has shown significant self-reported cognitive decline in older adults in relation to cannabis use.Cannabis metabolites are known to have an effect on cytochrome P450 enzymes, affecting the metabolism of medication, and increasing the susceptibility of older adults who use cannabis to adverse effects of polypharmacy. Finally, as research on emergency department visits by older adults shows, cannabis use can increase the risk of injury among this cohort.

As in the United States, cannabis use among older adults in Canada has increased significantly. The percentage of older adults who use cannabis in the Canadian province of Ontario, for example, reportedly doubled from 2005 to 2015. In response to this increase, and in anticipation of a rise in problematic use of cannabis and cannabis use disorder in older adults, the Canadian Coalition for Seniors’ Mental Health (through financial support from Substance Use and Addictions Program of Health Canada) has created guidelines on the prevention, assessment, and management of cannabis use disorder in older adults.

In the absence of a set of guidelines specific to the United States, the recommendations made by the coalition should be helpful in the care of older Americans. Among other recommendations, the guidelines highlight the needs for primary care physicians to build a better knowledge base around the use of cannabis in older adults, to screen older adults for cannabis use, and to educate older adults and their families about the risk of cannabis use.⁹

Cannabis use is increasingly popular among older adults¹⁰ for both medicinal and recreational purposes. Research and data supporting its medical benefits are limited, and the potential of harm from its use among older adults is present and significant. Importantly, many older adults who use marijuana have co-occurring mental health issues and substance use disorder(s).

Often, our older patients learn about benefits and harms of cannabis from friends and the Internet rather than from physicians and other clinicians.⁹ We must do our part to make sure that older patients understand the potential negative health impact that cannabis can have on their health. Physicians should screen older adults for marijuana use. Building a better knowledge base around changing trends and views in/on the use and accessibility of cannabis will help physicians better address cannabis use in older adults.
 

Mr. Kaleka is a medical student in the class of 2021 at Central Michigan University College of Medicine, Mount Pleasant. He has no disclosures. Mr. Kaleka would like to thank his mentor, Furhut Janssen, DO, for her continued guidance and support in research on mental health in vulnerable populations.

References

1. Vespa J et al. Demographic turning points for the United States: Population projections for 2020 to 2060. Current Population Reports. Washington: U.S. Census Bureau. 2020 Feb.

2. Han BH et al. Addiction. 2016 Oct 21. doi: 10.1111/add.13670.

3. Han BH and Palamar JJ. Drug Alcohol Depend. 2018 Oct;191:374-81.

4. Han BH and Palamar JJ. JAMA Intern Med. 2020 Feb 4;180(4):609-11.

5. Choi NG et al. Drug Alcohol Abuse. 2018;44(2):215-23.

6. Reynolds IR et al. J Am Griatr Soc. 2018 Nov;66(11):2167-71.

7. Ahmed AIA et al. J Am Geriatr Soc. 2014 Feb;62(2):410-1.

8. Lum HD et al. Gerontol Geriatr Med. 2019 Jan-Dec;5:2333721419843707.

9. Bertram JR et al. Can Geriatr J. 2020 Mar;23(1):135-42.

10. Baumbusch J and Yip IS. Clin Gerontol. 2020 Mar 29;1-7.

Older Americans – people aged 65 or older – make up 15% of the U.S. population, according to the Census Bureau. By the end of this decade, or the year 2030, this proportion will increase to 21% – and all “baby boomers,” those born between 1946 and 1964, will be older than 65.¹ Those demographic developments are occurring alongside a change in societal, legal, and public attitudes on cannabis.

VladK213/Getty Images

Liberalization of cannabis laws across the United States allows for ever easier access to medicinal and recreational cannabis. Traditionally, cannabis use, its effects, and related considerations in the adolescent and young adult populations have commanded significant research attention. Cannabis use in older adults, however, is not as well studied.² An exploration of trends in cannabis use by older adults and potential impact in terms of health is timely and important.

According to data from the National Survey on Drug Use and Health, cannabis use in adults aged 65 years and older appears to have been increasing steadily over the past 2 decades. Use among this group rose from 0.4% in 2006 and 2007, to 2.9% in 2015 and 2016.² And, most recently, use climbed from 3.7% in 2017 to 4.2% in 2018.²

Cannabis use also has risen among other adults. For those aged 50-64, cannabis use increased from 2.8% in 2006-2007 to 4.8% in 2012-2013.^2,3 Meanwhile, from 2015 to 2016, that number increased to 9.0%.^3,4

Past-year cannabis use in the groups of those aged 50-64 and those aged 65 and older appears to be higher in individuals with mental health problems, alcohol use disorder, and nicotine dependence.^5,6 Being male and being unmarried appear to be correlated with past-year cannabis use. Multimorbidity does not appear to be associated with past-year cannabis use. Those using cannabis tend to be long-term users and have first use at a much younger age, typically before age 21. Most older adults who report cannabis use do not perceive use to be of any risk or deem it only a slight risk.

Older adults use cannabis for both recreational and perceived medical benefits. Arthritis, chronic back pain, anxiety, depression, relaxation, stress reduction, and enhancement in terms of creativity are all purported reasons for use. However, there is limited to no evidence for the efficacy of cannabis in helping with those conditions and purposes. Clinical trials have shown that cannabis can be beneficial in managing pain and nausea, but those trials have not been conducted in older adults.^7,8

There is a real risk of cannabis use having a negative impact on the health of older adults. To begin with, the cannabis consumed today is significantly higher in potency than the cannabis that baby boomers were introduced to in their youth. The higher potency, combined with an age-related decline in function experienced by some older adults, makes them vulnerable to its known side effects, such as anxiety, dry mouth, tachycardia, high blood pressure, palpitations, wheezing, confusion, and dizziness.

Cannabis use is reported to bring a fourfold increase in cardiac events within the first hour of ingestion.⁹ Cognitive decline and memory impairment are well known adverse effects of cannabis use. Research has shown significant self-reported cognitive decline in older adults in relation to cannabis use.Cannabis metabolites are known to have an effect on cytochrome P450 enzymes, affecting the metabolism of medication, and increasing the susceptibility of older adults who use cannabis to adverse effects of polypharmacy. Finally, as research on emergency department visits by older adults shows, cannabis use can increase the risk of injury among this cohort.

As in the United States, cannabis use among older adults in Canada has increased significantly. The percentage of older adults who use cannabis in the Canadian province of Ontario, for example, reportedly doubled from 2005 to 2015. In response to this increase, and in anticipation of a rise in problematic use of cannabis and cannabis use disorder in older adults, the Canadian Coalition for Seniors’ Mental Health (through financial support from Substance Use and Addictions Program of Health Canada) has created guidelines on the prevention, assessment, and management of cannabis use disorder in older adults.

In the absence of a set of guidelines specific to the United States, the recommendations made by the coalition should be helpful in the care of older Americans. Among other recommendations, the guidelines highlight the needs for primary care physicians to build a better knowledge base around the use of cannabis in older adults, to screen older adults for cannabis use, and to educate older adults and their families about the risk of cannabis use.⁹

Cannabis use is increasingly popular among older adults¹⁰ for both medicinal and recreational purposes. Research and data supporting its medical benefits are limited, and the potential of harm from its use among older adults is present and significant. Importantly, many older adults who use marijuana have co-occurring mental health issues and substance use disorder(s).

Often, our older patients learn about benefits and harms of cannabis from friends and the Internet rather than from physicians and other clinicians.⁹ We must do our part to make sure that older patients understand the potential negative health impact that cannabis can have on their health. Physicians should screen older adults for marijuana use. Building a better knowledge base around changing trends and views in/on the use and accessibility of cannabis will help physicians better address cannabis use in older adults.
 

Mr. Kaleka is a medical student in the class of 2021 at Central Michigan University College of Medicine, Mount Pleasant. He has no disclosures. Mr. Kaleka would like to thank his mentor, Furhut Janssen, DO, for her continued guidance and support in research on mental health in vulnerable populations.

References

1. Vespa J et al. Demographic turning points for the United States: Population projections for 2020 to 2060. Current Population Reports. Washington: U.S. Census Bureau. 2020 Feb.

2. Han BH et al. Addiction. 2016 Oct 21. doi: 10.1111/add.13670.

3. Han BH and Palamar JJ. Drug Alcohol Depend. 2018 Oct;191:374-81.

4. Han BH and Palamar JJ. JAMA Intern Med. 2020 Feb 4;180(4):609-11.

5. Choi NG et al. Drug Alcohol Abuse. 2018;44(2):215-23.

6. Reynolds IR et al. J Am Griatr Soc. 2018 Nov;66(11):2167-71.

7. Ahmed AIA et al. J Am Geriatr Soc. 2014 Feb;62(2):410-1.

8. Lum HD et al. Gerontol Geriatr Med. 2019 Jan-Dec;5:2333721419843707.

9. Bertram JR et al. Can Geriatr J. 2020 Mar;23(1):135-42.

10. Baumbusch J and Yip IS. Clin Gerontol. 2020 Mar 29;1-7.

Older Americans – people aged 65 or older – make up 15% of the U.S. population, according to the Census Bureau. By the end of this decade, or the year 2030, this proportion will increase to 21% – and all “baby boomers,” those born between 1946 and 1964, will be older than 65.¹ Those demographic developments are occurring alongside a change in societal, legal, and public attitudes on cannabis.

VladK213/Getty Images

Liberalization of cannabis laws across the United States allows for ever easier access to medicinal and recreational cannabis. Traditionally, cannabis use, its effects, and related considerations in the adolescent and young adult populations have commanded significant research attention. Cannabis use in older adults, however, is not as well studied.² An exploration of trends in cannabis use by older adults and potential impact in terms of health is timely and important.

According to data from the National Survey on Drug Use and Health, cannabis use in adults aged 65 years and older appears to have been increasing steadily over the past 2 decades. Use among this group rose from 0.4% in 2006 and 2007, to 2.9% in 2015 and 2016.² And, most recently, use climbed from 3.7% in 2017 to 4.2% in 2018.²

Cannabis use also has risen among other adults. For those aged 50-64, cannabis use increased from 2.8% in 2006-2007 to 4.8% in 2012-2013.^2,3 Meanwhile, from 2015 to 2016, that number increased to 9.0%.^3,4

Past-year cannabis use in the groups of those aged 50-64 and those aged 65 and older appears to be higher in individuals with mental health problems, alcohol use disorder, and nicotine dependence.^5,6 Being male and being unmarried appear to be correlated with past-year cannabis use. Multimorbidity does not appear to be associated with past-year cannabis use. Those using cannabis tend to be long-term users and have first use at a much younger age, typically before age 21. Most older adults who report cannabis use do not perceive use to be of any risk or deem it only a slight risk.

Older adults use cannabis for both recreational and perceived medical benefits. Arthritis, chronic back pain, anxiety, depression, relaxation, stress reduction, and enhancement in terms of creativity are all purported reasons for use. However, there is limited to no evidence for the efficacy of cannabis in helping with those conditions and purposes. Clinical trials have shown that cannabis can be beneficial in managing pain and nausea, but those trials have not been conducted in older adults.^7,8

There is a real risk of cannabis use having a negative impact on the health of older adults. To begin with, the cannabis consumed today is significantly higher in potency than the cannabis that baby boomers were introduced to in their youth. The higher potency, combined with an age-related decline in function experienced by some older adults, makes them vulnerable to its known side effects, such as anxiety, dry mouth, tachycardia, high blood pressure, palpitations, wheezing, confusion, and dizziness.

Cannabis use is reported to bring a fourfold increase in cardiac events within the first hour of ingestion.⁹ Cognitive decline and memory impairment are well known adverse effects of cannabis use. Research has shown significant self-reported cognitive decline in older adults in relation to cannabis use.Cannabis metabolites are known to have an effect on cytochrome P450 enzymes, affecting the metabolism of medication, and increasing the susceptibility of older adults who use cannabis to adverse effects of polypharmacy. Finally, as research on emergency department visits by older adults shows, cannabis use can increase the risk of injury among this cohort.

As in the United States, cannabis use among older adults in Canada has increased significantly. The percentage of older adults who use cannabis in the Canadian province of Ontario, for example, reportedly doubled from 2005 to 2015. In response to this increase, and in anticipation of a rise in problematic use of cannabis and cannabis use disorder in older adults, the Canadian Coalition for Seniors’ Mental Health (through financial support from Substance Use and Addictions Program of Health Canada) has created guidelines on the prevention, assessment, and management of cannabis use disorder in older adults.

In the absence of a set of guidelines specific to the United States, the recommendations made by the coalition should be helpful in the care of older Americans. Among other recommendations, the guidelines highlight the needs for primary care physicians to build a better knowledge base around the use of cannabis in older adults, to screen older adults for cannabis use, and to educate older adults and their families about the risk of cannabis use.⁹

Cannabis use is increasingly popular among older adults¹⁰ for both medicinal and recreational purposes. Research and data supporting its medical benefits are limited, and the potential of harm from its use among older adults is present and significant. Importantly, many older adults who use marijuana have co-occurring mental health issues and substance use disorder(s).

Often, our older patients learn about benefits and harms of cannabis from friends and the Internet rather than from physicians and other clinicians.⁹ We must do our part to make sure that older patients understand the potential negative health impact that cannabis can have on their health. Physicians should screen older adults for marijuana use. Building a better knowledge base around changing trends and views in/on the use and accessibility of cannabis will help physicians better address cannabis use in older adults.
 

Mr. Kaleka is a medical student in the class of 2021 at Central Michigan University College of Medicine, Mount Pleasant. He has no disclosures. Mr. Kaleka would like to thank his mentor, Furhut Janssen, DO, for her continued guidance and support in research on mental health in vulnerable populations.

References

1. Vespa J et al. Demographic turning points for the United States: Population projections for 2020 to 2060. Current Population Reports. Washington: U.S. Census Bureau. 2020 Feb.

2. Han BH et al. Addiction. 2016 Oct 21. doi: 10.1111/add.13670.

3. Han BH and Palamar JJ. Drug Alcohol Depend. 2018 Oct;191:374-81.

4. Han BH and Palamar JJ. JAMA Intern Med. 2020 Feb 4;180(4):609-11.

5. Choi NG et al. Drug Alcohol Abuse. 2018;44(2):215-23.

6. Reynolds IR et al. J Am Griatr Soc. 2018 Nov;66(11):2167-71.

7. Ahmed AIA et al. J Am Geriatr Soc. 2014 Feb;62(2):410-1.

8. Lum HD et al. Gerontol Geriatr Med. 2019 Jan-Dec;5:2333721419843707.

9. Bertram JR et al. Can Geriatr J. 2020 Mar;23(1):135-42.

10. Baumbusch J and Yip IS. Clin Gerontol. 2020 Mar 29;1-7.

Continued use of the nonsteroidal drug (NSAID) meloxicam was associated with less reported knee osteoarthritis (OA) pain at 4 weeks compared with switching to a placebo in a randomized trial.

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.

Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).

“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.

They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.

“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.

The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.

The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.

The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.

Courtesy Dr. David Walsh

“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.

Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).

“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.

“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.

Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.

“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.

He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.

“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”

Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.

It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”

Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.

SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.

Continued use of the nonsteroidal drug (NSAID) meloxicam was associated with less reported knee osteoarthritis (OA) pain at 4 weeks compared with switching to a placebo in a randomized trial.

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.

Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).

“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.

They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.

“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.

The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.

The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.

The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.

Courtesy Dr. David Walsh

“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.

Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).

“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.

“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.

Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.

“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.

He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.

“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”

Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.

It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”

Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.

SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.

Continued use of the nonsteroidal drug (NSAID) meloxicam was associated with less reported knee osteoarthritis (OA) pain at 4 weeks compared with switching to a placebo in a randomized trial.

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was 6.7 out of a possible total of 20 for patients who continued meloxicam for 4 weeks versus 7.8 in those who stopped and switched to a placebo. The estimated mean difference in pain score was 1.4 (P = .92 for noninferiority), which is below the threshold of 2.1 that is considered to be the minimum clinically important difference.

Furthermore, patients who had switched to placebo and then subsequently participated in a telephone-based cognitive behavior therapy (CBT) program for another 10 weeks had higher pain levels compared with those who continued meloxicam. WOMAC scores were 12.1 and 11.8, respectively with a mean difference of 0.8 (P = .28 for noninferiority).

“Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam,” Liana Fraenkel, MD, MPH, of Yale University, New Haven, Conn., and coinvestigators concluded in their article, published in JAMA Internal Medicine.

They observed that the WOMAC pain score differences between the two groups were small, however, and that there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.

“Although the overall results of the trial are negative, they provide clinicians with data to support shared decision-making and reassure patients willing to taper NSAIDs and consider self-management approaches such as CBT,” Dr. Fraenkel and coauthors suggested.

The Stopping NSAIDs for Arthritis Pain trial had ultimately included 364 participants, 86% of whom were men, recruited from four veterans affairs health care systems. All had been taking NSAIDs for knee OA pain for at least 3 months and had participated in a 2-week run-in period where the NSAID they had been taking was switched to meloxicam, 15 mg once daily.

The aim of the trial had been to see if discontinuing NSAIDs and starting a CBT program would be noninferior to continuing NSAIDs in patients with knee OA.

The trial does not provide robust information on the use of CBT, David Walsh, a rheumatologist and director of the Pain Centre Versus Arthritis at the University of Nottingham, England, said in an interview.

Courtesy Dr. David Walsh

“It can’t tell you about efficacy of CBT,” Dr. Walsh said as the CBT part of the study was not randomized, was not controlled, and was unblinded. ”It would be a different task to design a CBT trial aiming to help people to stop taking tablets,” he added.

Dr. Fraenkel and coinvestigators had reported that, at week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (P = .28 for noninferiority).

“What the trial’s really doing is seeing whether people who’ve been on long-term nonsteroidals, can they just stop them without getting any worse? The conclusion for that is actually they are more likely to get worse than not if you just stop the nonsteroidals,” Dr. Walsh said.

“The withdrawal trial protocol is an important one. You can’t run a prospective trial for years to see whether something works for years. It is just not feasible. So actually, the protocol they’ve got of switching to placebo, or continuing with a nonsteroidal, is probably the best way of working out if an anti-inflammatory still has a pharmacological effect after actually being on it for X years,” Dr. Walsh said.

Dr. Walsh, who was not involved in the trial, observed that while the difference in pain scores between the groups was small, the deterioration in scores might be important for individual patients. Some may do worse, although granted that there may be some that might do better, he said.

“It is suggesting to me that nonsteroidals are still working in people who are on long-term treatment. It is not a very big pharmacological effect, but we already know from the RCTs of anti-inflammatory tablets, that they can be beneficial,” Dr. Walsh noted.

He also pointed out that patients’ pain had been improved after being switched from their current NSAID to meloxicam – the overall WOMAC pain score at recruitment was 9.6 and was 5.6 after the 2-week meloxicam run-in phase.

“Now, whether that’s because they’ve been switched to meloxicam, or whether it’s because they’re in a trial,” is an important question, Dr. Walsh suggested, adding that “it looks as though it’s more likely to be because they’re in a trial, because improvement was maintained during the following 4 weeks on placebo.”

Another point he made was that there was a higher percentage of patients in the placebo group that started taking other types of painkillers, just under half (46%) used acetaminophen versus a quarter (26%) of those who continued using meloxicam.

It is an interesting trial, “trying to tackle some really difficult questions and I think that there are really important implications from it that we can build on, but is it actually going to change the lives of patients at the moment? Not massively,” Dr. Walsh said, ”but it’s another step in the right direction.”

Dr. Fraenkel disclosed receiving research funding from the VA Office of Research and Development, the sponsor of the trial.

SOURCE: Fraenkel L et al. JAMA Intern Med. 2020 Jul 20. doi:10.1001/jamainternmed.2020.2821.

THE CASE

A 50-year-old man presented to the primary care office for evaluation of foot pain. The day before, his left fifth toe had become exquisitely tender. He distinctly remembered that when he awoke, there was no discoloration or pain, but the toe later became “purple.” He denied any trauma. His medical record was notable for an extensive smoking history and a family history of early cardiovascular disease.

The patient appeared well but in obvious distress, secondary to the pain. His vital signs were unremarkable. His head, neck, lung, and cardiac exams revealed no abnormalities. Physical examination revealed a left fifth toe that was dusky purple and warm to the touch. Pain disproportionate to examination was noted on the anterior aspect of the toe, with limited range of motion. The patient walked with a compensated gait. Pulses were palpable on the posterior tibial (PT) and dorsalis pedis (DP) regions.

DIAGNOSIS

Based on our exam findings, we suspected a vascular injury and recommended an emergency consult by Podiatry, for which he was scheduled the following morning. The podiatric evaluation confirmed concern for a vascular injury and prompted a request for an emergent evaluation by Vascular Surgery.

The patient was seen emergently on Day 4 for a vascular surgery evaluation. Examination at that time showed a nearly absent femoral pulse on the left side and diminished and monophasic DP and PT pulses. His left foot demonstrated nonblanchable purpura that was clinically consistent with cholesterol embolization syndrome (CES).

We calculated the patient’s ankle-brachial index, and computed tomography angiography (CTA) was performed. While results were pending, the patient was started on aspirin 81 mg, clopidogrel 75 mg, and atorvastatin 40 mg, for a suspected slowly progressing iliac artery stenosis with a resulting acute atheroembolic event.

The CTA report showed a high-grade stenosis at the bifurcation of the left iliac artery, extending into both external and internal arteries. Of note, mild atherosclerotic disease without significant occlusion and runoff to the foot was observed into the tibial arteries. The stenosis extended into the profonda femoris artery, as well.

DISCUSSION

Atherosclerotic plaques are commonly encountered in patients with atherosclerotic disease; however, there are 2 varieties of emboli that arise from these plaques and one is often overlooked.^1-4 The more common of these variants, thromboemboli, originates from an atherosclerotic plaque and can become lodged in a medium or large vessel as a single embolus.

Continue to: By contrast...

By contrast, atheroemboli (commonly known as cholesterol emboli or cholesterol crystal embolization) originate from atherosclerotic plaques in the aorta or another large artery,⁵ which are prone to embolize if the underlying plaque experiences stress. As the plaque erodes, cholesterol crystals break off and embolize distally. These smaller crystals flood into the circulation, allowing a shower of emboli over time to occlude the arterioles. As occlusion spreads through the arterioles, multiple organ systems are affected. (It was previously thought that procedure-associated cases were common, but a literature review has not borne this out.⁵)

The shower of emboli often triggers a systemic inflammatory response, causing nondescript abnormalities of laboratory inflammatory markers.^6,7 Interestingly, hypereosinophilia is noted in about 80% of patients with CES.⁸It is not uncommon for atheroemboli of the lower extremity to manifest, as it did in this case, as “blue toe syndrome.”

No disease-specific testing. A confounding factor in validating the diagnosis of CES is the lack of disease-specific testing. However, CES should be considered in a patient with acute kidney injury and hypereosinophilia. Making the diagnosis requires a high degree of clinical suspicion. Any organ can be affected, although the brain, kidneys, gastrointestinal tract, skin, and skeletal muscles of the lower extremities are most frequently involved.⁹ If left undiagnosed, the results can be devastating: slow and chronic injury to a variety of organ systems over time, which may not be recognized as a harbinger of an insidious underlying process causing end-organ damage.

Technically, definitive diagnosis can be made by biopsy of an affected organ. However, biopsy’s utility is limited due to potential for sampling error, accessibility (as noted, the location of the involved organ[s] may make biopsy nearly impossible without additional surgical risk⁹), and risk of poor healing to the biopsy site.¹⁰

Treatment is two-fold: supportive care for the affected end organ and prevention of subsequent embolic events. The latter entails aggressive risk factor reduction strategies, such as smoking cessation, statin therapy, blood pressure control, and blood sugar control. Warfarin is not recommended for treatment of CES due to the risk of further plaque rupture, hemorrhage, acute and chronic renal failure, and cholesterol microembolization to other organs.^11,12

Continue to: Our patient

Our patient. After testing confirmed the diagnosis, the patient underwent an angioplasty. A stent was placed in his left iliac artery. He was continued on antiplatelet and statin therapy and was again counseled regarding smoking cessation.

THE TAKEAWAY

When patients present with symptoms suggestive of a vascular origin, consider CES. Although it can affect a multitude of organs, acute kidney injury and hypereosinophilia are the most common signs. Immediate intervention is required to save the affected organ; strategizing to reduce the risk for further embolic events is also key.

Warfarin is not recommended for treatment of cholesterol embolization syndrome due to the risk of further plaque rupture, hemorrhage, and cholesterol microembolization to other organs.

Prompt recognition of vascular emergencies, including those that are harbingers of atherosclerotic disease, is essential. As clinicians, it is imperative that we use all resources to address significant population health burdens. If CES is more prevalent than commonly thought, consideration should be given to increasing education about early detection and treatment of this disorder, including the reinforcement of primary prevention and aggressive treatment of risk factors for atherosclerotic cardiovascular disease.

CORRESPONDENCE
Meagan Vermeulen, MD, FAAFP, Department of Family Medicine, Rowan University School of Osteopathic Medicine, 42 East Laurel Road, Suite 2100A, Stratford, NJ 08084; vermeulen@rowan.edu

THE CASE

A 50-year-old man presented to the primary care office for evaluation of foot pain. The day before, his left fifth toe had become exquisitely tender. He distinctly remembered that when he awoke, there was no discoloration or pain, but the toe later became “purple.” He denied any trauma. His medical record was notable for an extensive smoking history and a family history of early cardiovascular disease.

The patient appeared well but in obvious distress, secondary to the pain. His vital signs were unremarkable. His head, neck, lung, and cardiac exams revealed no abnormalities. Physical examination revealed a left fifth toe that was dusky purple and warm to the touch. Pain disproportionate to examination was noted on the anterior aspect of the toe, with limited range of motion. The patient walked with a compensated gait. Pulses were palpable on the posterior tibial (PT) and dorsalis pedis (DP) regions.

DIAGNOSIS

Based on our exam findings, we suspected a vascular injury and recommended an emergency consult by Podiatry, for which he was scheduled the following morning. The podiatric evaluation confirmed concern for a vascular injury and prompted a request for an emergent evaluation by Vascular Surgery.

The patient was seen emergently on Day 4 for a vascular surgery evaluation. Examination at that time showed a nearly absent femoral pulse on the left side and diminished and monophasic DP and PT pulses. His left foot demonstrated nonblanchable purpura that was clinically consistent with cholesterol embolization syndrome (CES).

We calculated the patient’s ankle-brachial index, and computed tomography angiography (CTA) was performed. While results were pending, the patient was started on aspirin 81 mg, clopidogrel 75 mg, and atorvastatin 40 mg, for a suspected slowly progressing iliac artery stenosis with a resulting acute atheroembolic event.

The CTA report showed a high-grade stenosis at the bifurcation of the left iliac artery, extending into both external and internal arteries. Of note, mild atherosclerotic disease without significant occlusion and runoff to the foot was observed into the tibial arteries. The stenosis extended into the profonda femoris artery, as well.

DISCUSSION

Atherosclerotic plaques are commonly encountered in patients with atherosclerotic disease; however, there are 2 varieties of emboli that arise from these plaques and one is often overlooked.^1-4 The more common of these variants, thromboemboli, originates from an atherosclerotic plaque and can become lodged in a medium or large vessel as a single embolus.

Continue to: By contrast...

By contrast, atheroemboli (commonly known as cholesterol emboli or cholesterol crystal embolization) originate from atherosclerotic plaques in the aorta or another large artery,⁵ which are prone to embolize if the underlying plaque experiences stress. As the plaque erodes, cholesterol crystals break off and embolize distally. These smaller crystals flood into the circulation, allowing a shower of emboli over time to occlude the arterioles. As occlusion spreads through the arterioles, multiple organ systems are affected. (It was previously thought that procedure-associated cases were common, but a literature review has not borne this out.⁵)

The shower of emboli often triggers a systemic inflammatory response, causing nondescript abnormalities of laboratory inflammatory markers.^6,7 Interestingly, hypereosinophilia is noted in about 80% of patients with CES.⁸It is not uncommon for atheroemboli of the lower extremity to manifest, as it did in this case, as “blue toe syndrome.”

No disease-specific testing. A confounding factor in validating the diagnosis of CES is the lack of disease-specific testing. However, CES should be considered in a patient with acute kidney injury and hypereosinophilia. Making the diagnosis requires a high degree of clinical suspicion. Any organ can be affected, although the brain, kidneys, gastrointestinal tract, skin, and skeletal muscles of the lower extremities are most frequently involved.⁹ If left undiagnosed, the results can be devastating: slow and chronic injury to a variety of organ systems over time, which may not be recognized as a harbinger of an insidious underlying process causing end-organ damage.

Technically, definitive diagnosis can be made by biopsy of an affected organ. However, biopsy’s utility is limited due to potential for sampling error, accessibility (as noted, the location of the involved organ[s] may make biopsy nearly impossible without additional surgical risk⁹), and risk of poor healing to the biopsy site.¹⁰

Treatment is two-fold: supportive care for the affected end organ and prevention of subsequent embolic events. The latter entails aggressive risk factor reduction strategies, such as smoking cessation, statin therapy, blood pressure control, and blood sugar control. Warfarin is not recommended for treatment of CES due to the risk of further plaque rupture, hemorrhage, acute and chronic renal failure, and cholesterol microembolization to other organs.^11,12

Continue to: Our patient

Our patient. After testing confirmed the diagnosis, the patient underwent an angioplasty. A stent was placed in his left iliac artery. He was continued on antiplatelet and statin therapy and was again counseled regarding smoking cessation.

THE TAKEAWAY

When patients present with symptoms suggestive of a vascular origin, consider CES. Although it can affect a multitude of organs, acute kidney injury and hypereosinophilia are the most common signs. Immediate intervention is required to save the affected organ; strategizing to reduce the risk for further embolic events is also key.

Warfarin is not recommended for treatment of cholesterol embolization syndrome due to the risk of further plaque rupture, hemorrhage, and cholesterol microembolization to other organs.

Prompt recognition of vascular emergencies, including those that are harbingers of atherosclerotic disease, is essential. As clinicians, it is imperative that we use all resources to address significant population health burdens. If CES is more prevalent than commonly thought, consideration should be given to increasing education about early detection and treatment of this disorder, including the reinforcement of primary prevention and aggressive treatment of risk factors for atherosclerotic cardiovascular disease.

CORRESPONDENCE
Meagan Vermeulen, MD, FAAFP, Department of Family Medicine, Rowan University School of Osteopathic Medicine, 42 East Laurel Road, Suite 2100A, Stratford, NJ 08084; vermeulen@rowan.edu

THE CASE

A 50-year-old man presented to the primary care office for evaluation of foot pain. The day before, his left fifth toe had become exquisitely tender. He distinctly remembered that when he awoke, there was no discoloration or pain, but the toe later became “purple.” He denied any trauma. His medical record was notable for an extensive smoking history and a family history of early cardiovascular disease.

The patient appeared well but in obvious distress, secondary to the pain. His vital signs were unremarkable. His head, neck, lung, and cardiac exams revealed no abnormalities. Physical examination revealed a left fifth toe that was dusky purple and warm to the touch. Pain disproportionate to examination was noted on the anterior aspect of the toe, with limited range of motion. The patient walked with a compensated gait. Pulses were palpable on the posterior tibial (PT) and dorsalis pedis (DP) regions.

DIAGNOSIS

Based on our exam findings, we suspected a vascular injury and recommended an emergency consult by Podiatry, for which he was scheduled the following morning. The podiatric evaluation confirmed concern for a vascular injury and prompted a request for an emergent evaluation by Vascular Surgery.

The patient was seen emergently on Day 4 for a vascular surgery evaluation. Examination at that time showed a nearly absent femoral pulse on the left side and diminished and monophasic DP and PT pulses. His left foot demonstrated nonblanchable purpura that was clinically consistent with cholesterol embolization syndrome (CES).

We calculated the patient’s ankle-brachial index, and computed tomography angiography (CTA) was performed. While results were pending, the patient was started on aspirin 81 mg, clopidogrel 75 mg, and atorvastatin 40 mg, for a suspected slowly progressing iliac artery stenosis with a resulting acute atheroembolic event.

The CTA report showed a high-grade stenosis at the bifurcation of the left iliac artery, extending into both external and internal arteries. Of note, mild atherosclerotic disease without significant occlusion and runoff to the foot was observed into the tibial arteries. The stenosis extended into the profonda femoris artery, as well.

DISCUSSION

Atherosclerotic plaques are commonly encountered in patients with atherosclerotic disease; however, there are 2 varieties of emboli that arise from these plaques and one is often overlooked.^1-4 The more common of these variants, thromboemboli, originates from an atherosclerotic plaque and can become lodged in a medium or large vessel as a single embolus.

Continue to: By contrast...

By contrast, atheroemboli (commonly known as cholesterol emboli or cholesterol crystal embolization) originate from atherosclerotic plaques in the aorta or another large artery,⁵ which are prone to embolize if the underlying plaque experiences stress. As the plaque erodes, cholesterol crystals break off and embolize distally. These smaller crystals flood into the circulation, allowing a shower of emboli over time to occlude the arterioles. As occlusion spreads through the arterioles, multiple organ systems are affected. (It was previously thought that procedure-associated cases were common, but a literature review has not borne this out.⁵)

The shower of emboli often triggers a systemic inflammatory response, causing nondescript abnormalities of laboratory inflammatory markers.^6,7 Interestingly, hypereosinophilia is noted in about 80% of patients with CES.⁸It is not uncommon for atheroemboli of the lower extremity to manifest, as it did in this case, as “blue toe syndrome.”

No disease-specific testing. A confounding factor in validating the diagnosis of CES is the lack of disease-specific testing. However, CES should be considered in a patient with acute kidney injury and hypereosinophilia. Making the diagnosis requires a high degree of clinical suspicion. Any organ can be affected, although the brain, kidneys, gastrointestinal tract, skin, and skeletal muscles of the lower extremities are most frequently involved.⁹ If left undiagnosed, the results can be devastating: slow and chronic injury to a variety of organ systems over time, which may not be recognized as a harbinger of an insidious underlying process causing end-organ damage.

Technically, definitive diagnosis can be made by biopsy of an affected organ. However, biopsy’s utility is limited due to potential for sampling error, accessibility (as noted, the location of the involved organ[s] may make biopsy nearly impossible without additional surgical risk⁹), and risk of poor healing to the biopsy site.¹⁰

Treatment is two-fold: supportive care for the affected end organ and prevention of subsequent embolic events. The latter entails aggressive risk factor reduction strategies, such as smoking cessation, statin therapy, blood pressure control, and blood sugar control. Warfarin is not recommended for treatment of CES due to the risk of further plaque rupture, hemorrhage, acute and chronic renal failure, and cholesterol microembolization to other organs.^11,12

Continue to: Our patient

Our patient. After testing confirmed the diagnosis, the patient underwent an angioplasty. A stent was placed in his left iliac artery. He was continued on antiplatelet and statin therapy and was again counseled regarding smoking cessation.

THE TAKEAWAY

When patients present with symptoms suggestive of a vascular origin, consider CES. Although it can affect a multitude of organs, acute kidney injury and hypereosinophilia are the most common signs. Immediate intervention is required to save the affected organ; strategizing to reduce the risk for further embolic events is also key.

Warfarin is not recommended for treatment of cholesterol embolization syndrome due to the risk of further plaque rupture, hemorrhage, and cholesterol microembolization to other organs.

Prompt recognition of vascular emergencies, including those that are harbingers of atherosclerotic disease, is essential. As clinicians, it is imperative that we use all resources to address significant population health burdens. If CES is more prevalent than commonly thought, consideration should be given to increasing education about early detection and treatment of this disorder, including the reinforcement of primary prevention and aggressive treatment of risk factors for atherosclerotic cardiovascular disease.

CORRESPONDENCE
Meagan Vermeulen, MD, FAAFP, Department of Family Medicine, Rowan University School of Osteopathic Medicine, 42 East Laurel Road, Suite 2100A, Stratford, NJ 08084; vermeulen@rowan.edu

Which antibiotics are most useful for infection following ear piercing? When is it safe to attempt removal of a foreign body from the ear canal, and which cerumenolytic agent may be best for ear wax? This review covers common ailments of the outer ear, which are often readily diagnosed given a patient’s history and thorough physical examination. We also address more complicated matters such as deciding when to refer for treatment of suspected malignant otitis externa, and which lab markers to follow when managing it yourself.

A (very) brief review of ear anatomy

Understanding the unique embryology and intricate anatomy of the external ear informs our understanding of predictable infections, growths, and malformations.

The external ear is composed of the external auditory canal and auricle. The external auditory canal has a lateral (external) cartilaginous portion and a medial (internal) bony portion. The auricular structure is complex and formed by the helix, antihelix (crura; scaphoid fossa), tragus, antitragus, conchae, and lobule. The auricle is composed of elastic cartilage covered by skin. The lobule is composed of skin, adipose tissue, and connective tissue.

Embryologically, the auricle, auditory canal, and middle ear form from ectoderm of the first 2 branchial arches during early gestation. The auricle forms from the fusion of soft-tissue swellings (hillocks). Three hillocks arise from the first branchial arch and 3 from the second branchial arch during the fifth and sixth weeks of gestation. Tissues from the second branchial arch comprise the lobule, antihelix, and caudal helix. The cartilage of the tragus forms from the first branchial arch. The ear canal forms from an epithelial invagination of the first branchial arch that also occurs during the fifth week of gestation.¹

Infections

Perichondritis

Inflammation or infection of the connective tissue layer surrounding the auricular cartilage (perichondrium) results in perichondritis. Further extension of infection can lead to an auricular abscess. Both of these conditions can have serious consequences.

What you’ll see. The most common risk factor for perichondritis is the popular practice of cosmetic transcartilaginous piercing.² Piercing of the helix, scapha, or anti-helix (often referred to as “high” ear piercing) causes localized trauma that can strip the adjacent perichondrium, decrease blood supply, create cartilaginous microfractures, and lead to devascularization. Rates of infection as high as 35% have been reported with high-ear piercing.³

Rates of infection as high as 35% have been reported with high-ear piercing.

The most common microbes associated with perichondritis and pinna abscess formation are Pseudomonas and Staphylococcus species.² P aeruginosa accounts for a majority (87%) of post-piercing infections of the auricular cartilage.²

Continue to: How to treat

How to treat. The cornerstone of treatment is early detection and antimicrobial coverage with antipseudomonal antibiotics. Ciprofloxacin is the oral antibiotic of choice because of its ability to penetrate the tissue.⁴ Other options include clindamycin and third- or fourth-generation cephalosporins. If the wound becomes abscessed, ­perform (or refer for) early surgical incision and drainage.⁵ A failure to promptly recognize perichondritis or to mistakenly prescribe non-­antipseudomonal antibiotics contributes to increased rates of hospitalization.² Cosmetic deformity is the most common complication of perichondritis. This may require reconstructive surgery.

Otitis externa

Acute otitis externa (AOE; “swimmer’s ear”) is cellulitis of the skin and subdermis of the external ear canal. It is most prevalent in warm, moist climates and almost always associated with acute bacterial infection, most commonly P aeruginosa or S aureus.⁶ There is also an increased association with poor water quality (containing higher bacterial loads). Anything breaching the integrity of the ear canal can potentially predispose to the development of AOE. This includes trauma from cleaning, cerumen removal, scratching due to allergic conditions, and placement of hearing-aid devices.⁶

What you’ll see. Suspect AOE when signs or symptoms of ear canal inflammation have appeared rapidly (generally within 2 days) over the past 3 weeks.⁷ Findings include otalgia, itching, fullness, tragal tenderness, ear canal edema, erythema with or without otorrhea, lymphadenitis, or cellulitis of the pinna or adjacent skin.⁷ AOE must be distinguished from other causes of otalgia and otorrhea, including dermatitis and viral infection.

How to treat. Topical therapy is recommended for the initial treatment of uncomplicated AOE, usually given over 7 days. Multiple topical preparations are available, such as ciprofloxacin 0.2%/hydrocortisone 1.0%; neomycin/polymyxin B/hydrocortisone; ofloxacin 0.3%; or acetic acid 2.0%.⁷ Avoid these agents, though, if you suspect tympanic membrane rupture. Quinolone drops are the only topical antimicrobials approved for middle ear use.⁷

Systemic antibiotics are not recommended for the initial treatment of AOE. Topical agents deliver a much higher concentration of medication than can be achieved systemically. Consider systemic antibiotics if there is extension outside the ear canal, a concern for necrotizing otitis externa (more on this in a bit), or the patient is immunodeficient.⁸

Continue to: Patient (or parent) education...

Patient (or parent) education is important to ensure proper medication administration. The patient should lie down with the affected ear facing up. After the canal is filled with drops, the patient should remain in this position for 3 to 5 minutes. Gently massaging the tragus can augment delivery. Patients should keep the ear canal as dry as possible and avoid inserting objects (eg, hearing aids, ear buds, cotton-tipped applicators) into the canal for the duration of treatment. The delivery of topical antibiotics can be enhanced by wick placement. Prescribe analgesics (typically nonsteroidal anti-inflammatory agents) based on severity of pain.⁷

Have patients abstain from water sports for 7 to 10 days. Showering is acceptable with minimal ear exposure to water; bathing is preferred when possible. If there is no clinical improvement in 48 to 72 hours, ask patients to return for re-evaluation.⁸ Prevention is essential for patients with a history of recurrent otitis externa. Acetic acid solutions create an acidic environment within the canal to help prevent recurrent AOE. Ear plugs and petroleum jelly–soaked cotton plugs prior to water exposure may also help prevent recurrent AOE.

Malignant otitis externa

Malignant, or necrotizing, otitis externa is an aggressive disease form of otitis externa that is most common in individuals with diabetes or other immunodeficiency disorders.⁹ Most cases are due to infection with P aeruginosa.¹⁰ Prior to the availability of effective antibiotics, mortality rates in patients with necrotizing otitis externa were as high as 50%.¹¹

What you’ll see. Patients typically present with severe ear pain, otorrhea, conductive hearing loss, and a feeling of fullness in the external ear canal. Physical examination reveals purulent otorrhea and a swollen, tender ear canal. Exposed bone may be visible, most often on the floor of the canal. The tympanic membrane and middle ear are seldom involved on initial presentation.

The infection often originates at the junction of the bony and cartilaginous portion of the external canal, spreading through the fissures of Santorini to the skull base. If not aggressively treated, the infection spreads medially to the tympanomastoid suture causing intracranial complications—usually a facial nerve neuropathy.

Continue to: Given these clinical findings...

Given these clinical findings, promptly order laboratory studies and imaging to confirm the diagnosis. The erythrocyte sedimentation rate and C-reactive protein level are typically elevated, and either can be used as a marker to follow treatment. Computed tomography (CT) helps to determine the location and extent of disease and is recommended as the initial diagnostic imaging modality for patients with suspected malignant otitis externa.¹²

Magnetic resonance imaging helps define soft-tissue changes, dural enhancement, and involvement of medullary bone, making this the preferred modality to monitor therapeutic response.¹² Technetium bone scanning can also be used for the initial diagnosis (particularly if CT findings are normal and clinical suspicion is high) and for follow-up with treatment.

How to treat. Management involves a team approach with otolaryngology, radiology, neurology, endocrinology, and infectious disease specialists. Long term (6-8 weeks) antipseudomonal antibiotic treatment is typical.

In head-to-head laboratory comparisons, distilled water appears to be the best cerumenolytic.

Let culture results guide the choice of antibiotic. Fluoroquinolone therapy, usually ciprofloxacin, is used most often.¹² Surgical intervention may be required for local debridement and drainage of abscesses. Close follow-up is necessary due to reports of recurrence up to 1 year after treatment. If left untreated, necrotizing otitis externa can lead to osteomyelitis, meningitis, septic thrombosis, cerebral abscess, and death.¹¹

Cerumen impaction

The relatively small diameter of the external auditory canal increases the risk for impaction of cerumen and foreign bodies. Cerumen impaction, in particular, is a common primary care complaint. Cerumen forms when glandular secretions from the outer two-thirds of the ear canal mix with exfoliated skin. It functions as a lubricant for the ear canal and as a barrier against infection, water accumulation, and foreign bodies.¹³

Continue to: What you'll see

What you’ll see. You may encounter cerumen impaction in an asymptomatic patient when it prevents visualization of the external auditory canal or tympanic membrane, or when a patient complains of conductive hearing loss, tinnitus, dizziness, ear pain, itching, and cough.¹³ It is found in 1 in 10 children and 1 in 20 adults.¹³ There is a higher incidence in patients who are elderly, are cognitively impaired, or wear hearing devices or ear plugs.^13,14 Asymptomatic cerumen impaction should not be treated. A recent clinical guideline provides a useful “do and don’t” list for patient education (TABLE).¹³

How to treat. In asymptomatic patients, the presence of cerumen on examination is not an indication for removal. Based on current guidelines,¹³ impacted cerumen can safely be removed from the ear canal of symptomatic patients in several ways:

• Manual removal with cerumen loop/spoon or alligator forceps. This method decreases the risk for infection because it limits moisture exposure. However, it should be performed by a health care provider trained in its use because of the risk for trauma to the ear canal and tympanic membrane.
• Irrigation of the ear using tap water or a 50-50 solution of hydrogen peroxide and water. Irrigation can be achieved with a syringe or jet irrigator using a modified tip. This method also has a risk for trauma to the ear canal and tympanic membrane and should only be performed by appropriately trained health care professionals.
• Use of cerumenolytic agents to soften and thin earwax and promote natural extrusion. Several types of cerumenolytic drops (water-based and oil-based) are available and appear to be equally effective. Water-based solutions contain hydrogen peroxide, docusate sodium, acetic acid, and sodium bicarbonate. Oil-based drops may contain peanut, almond, or olive oils. A thorough allergic history should be performed to avoid using products in patients with nut allergies. In head-to-head laboratory comparisons, distilled water appears to be the best cerumenolytic.¹⁵

Foreign bodies

Foreign bodies in the external auditory canal (typically beads, cotton tips, and insects) are more common in children than adults.¹⁶

What you’ll see. Most foreign bodies are lodged in the bony part of the external auditory canal, and many patients try to remove the object before seeking medical care. Removal requires adequate visualization and skill.¹⁷ Although patients may be asymptomatic, most complain of pain, fullness, decreased hearing, or otorrhea.

How to treat. Directly visible objects can often be removed without referral. Suction, irrigation, forceps, probes, and fine hooks have been used. Insect removal can be facilitated by first flooding the canal with xylocaine, alcohol, or mineral oil. Acetone may be used to dissolve foreign bodies containing Styrofoam or to loosen glues. If the object is a button battery, avoid irrigation to prevent liquefaction tissue necrosis.

Continue to: Complications of foreign body removal...

Insect removal can be facilitated by first flooding the canal with xylocaine, alcohol, or mineral oil.

Complications of foreign body removal include pain, otitis externa, otitis media, and trauma to the ear or tympanic membrane. The likelihood of successful removal of the object decreases and the risk for complications increases with each subsequent attempt.¹⁷ Consult an otolaryngologist if sedation or anesthesia is required, the foreign body is tightly wedged, there is trauma to the ear canal or tympanic membrane, the foreign body has a sharp edge (eg, glass or wire), or removal attempts have been unsuccessful.

Trauma

Sports injuries, motor vehicle accidents, bites, falls, and burns are the primary causes of trauma to the external ear.¹⁸

What you’ll see. Blunt auricular trauma predisposes to infection, necrosis, and scar contracture. One of the most common sequelae is cauliflower ear. Trauma is particularly common with contact sports such as boxing, wrestling, or mixed martial arts. The skin of the auricle attaches directly to the perichondrium. Following blunt or shearing trauma to the auricle, hematomas form within the space between the perichondrium and cartilage of the anterior ear.¹⁹Following hematoma formation, the healing process brings chondrocytes and fibroblasts to the subperichondrial space, promoting fibrocartilage formation. Over time (and with repeated injury), this can lead to a chronic, bulbous deformity known as cauliflower ear.

How to treat. Small hematomas can be managed by aspiration, while larger ones generally require open drainage.²⁰ Newer treatments involving pressure dressings and the use of fibrin glue have been proposed.²⁰ Recommend that athletes participating in contact sports wear appropriate protective headgear to prevent auricular hematoma and cauliflower ear.

Neoplasm

Roughly 5% of all skin cancers involve the ear, most frequently the pinna due to chronic sun exposure.²¹ The most frequently occurring malignancy of the external ear is basal cell carcinoma (BCC), which is responsible for 80% of all nonmelanoma skin cancers.²²

Continue to: What you'll see

What you’ll see. BCC of the ear usually involves the preauricular area and the helix. The risk for BCC is related to exposure to ultraviolet radiation. BCC of the ear is more common in men and can be particularly aggressive, highlighting the importance of prevention and prompt recognition. BCC typically presents as a fleshy papule that is often translucent or “pearly’” and has overlying telangiectasia and a “rolled” border. Central ulceration can occur as well.

How to treat. Usual treatment of BCC is surgical excision. Prevention is critical and centers on sun avoidance or the use of appropriate sunscreens.

If the object in the external auditory canal is a button battery, avoid irrigation to prevent liquefaction tissue necrosis.

In addition to BCC, exposure of the external ear to sunlight and ultraviolet radiation predisposes patients to the development of squamous cell carcinoma (SCC) and melanoma. SCC has a variety of presentations including papules, plaques, and nodules. SCC has a higher metastatic potential than does BCC.

Keloid

Keloids are an abnormal healing response to soft-tissue injury: benign fibrocartilaginous growths that extend beyond the original wound.

What you’ll see. Keloids are more common in dark-skinned individuals and tend to result from burns, surgical incisions, infection, trauma, tattooing, injections, piercings, and arthropod bites. In some cases, they arise spontaneously. Keloids are more common in areas of increased skin tension (chest, shoulders, back), but may occur on the ears—most commonly after piercing or trauma. Keloids present clinically as slow-growing rubbery or firm nodules. The diagnosis is typically based on clinical appearance but can be confirmed by histopathology.

Continue to: How to treat

How to treat. Treatments vary and include observation, excision, intralesional injections, cryotherapy, enzyme therapy, silicone gel application, and irradiation.²³ Recurrence is common; no therapy has been proven to be universally superior or preferred.

Congenital malformations

Atresia

Disruption of embryologic development (failed invagination of the external auditory canal) can lead to a stenotic or absent ear canal (aural atresia). Aural atresia is also often associated with fusion of the incus and malleus. This condition occurs predominantly in males. Unilateral atresia is more common than bilateral atresia, and the right ear is more often involved than the left.²⁴

Microtia

Microtia is the incomplete development of the pinna leading to a small or deformed pinna. Microtia can be unilateral or bilateral. As with atresia, microtia more commonly affects males and, if unilateral, the right side is more often affected than the left. Microtia can occur in isolation but is often associated with genetic syndromes such as Treacher Collins syndrome and craniofacial microsomia (Goldenhar syndrome). When microtia is identified (typically at birth or early infancy), audiologic testing and a thorough physical examination for evidence of associated defects should be performed. Consult with an audiologist, clinical geneticist, or pediatric otolaryngologist.

Pre-auricular pits

Pre-auricular pits (sinuses) are tiny indentations anterior to the helix and superior to the tragus. While pre-auricular pits are more common on the right side, they are bilateral in 25% to 50% of cases.²⁵ Pre-auricular pits occur in up to 1% of white children, 5% of black children, and 10% of Asian children.²⁵ Children with this condition should undergo formal audiologic testing as their risk for hearing loss is higher compared with the general population.²⁶

Directly visible foreign objects can often be removed without referral, but the likelihood of success decreases with each subsequent attempt.

The branchio-oto-renal syndrome (associated with pre-auricular pits and hearing loss) also features structural defects of the ear, renal anomalies and/or nasolacrimal duct stenosis or fistulas. If this syndrome is suspected, renal ultrasound imaging is warranted. Other indications for renal ultrasound in patients with a pre-auricular pit are any dysmorphic feature, a family history of deafness, an auricular malformation, or a maternal history of gestational diabetes.²⁷ Pre-auricular pits do not require surgery unless they drain chronically or become recurrently infected. Complete surgical excision is the treatment of choice in these cases.

CORRESPONDENCE 
Mark Stephens, MD, 1850 Park Avenue, State College, PA 16801; mstephens3@pennstatehealth.psu.edu

Which antibiotics are most useful for infection following ear piercing? When is it safe to attempt removal of a foreign body from the ear canal, and which cerumenolytic agent may be best for ear wax? This review covers common ailments of the outer ear, which are often readily diagnosed given a patient’s history and thorough physical examination. We also address more complicated matters such as deciding when to refer for treatment of suspected malignant otitis externa, and which lab markers to follow when managing it yourself.

A (very) brief review of ear anatomy

Understanding the unique embryology and intricate anatomy of the external ear informs our understanding of predictable infections, growths, and malformations.

The external ear is composed of the external auditory canal and auricle. The external auditory canal has a lateral (external) cartilaginous portion and a medial (internal) bony portion. The auricular structure is complex and formed by the helix, antihelix (crura; scaphoid fossa), tragus, antitragus, conchae, and lobule. The auricle is composed of elastic cartilage covered by skin. The lobule is composed of skin, adipose tissue, and connective tissue.

Embryologically, the auricle, auditory canal, and middle ear form from ectoderm of the first 2 branchial arches during early gestation. The auricle forms from the fusion of soft-tissue swellings (hillocks). Three hillocks arise from the first branchial arch and 3 from the second branchial arch during the fifth and sixth weeks of gestation. Tissues from the second branchial arch comprise the lobule, antihelix, and caudal helix. The cartilage of the tragus forms from the first branchial arch. The ear canal forms from an epithelial invagination of the first branchial arch that also occurs during the fifth week of gestation.¹

Infections

Perichondritis

Inflammation or infection of the connective tissue layer surrounding the auricular cartilage (perichondrium) results in perichondritis. Further extension of infection can lead to an auricular abscess. Both of these conditions can have serious consequences.

What you’ll see. The most common risk factor for perichondritis is the popular practice of cosmetic transcartilaginous piercing.² Piercing of the helix, scapha, or anti-helix (often referred to as “high” ear piercing) causes localized trauma that can strip the adjacent perichondrium, decrease blood supply, create cartilaginous microfractures, and lead to devascularization. Rates of infection as high as 35% have been reported with high-ear piercing.³

Rates of infection as high as 35% have been reported with high-ear piercing.

The most common microbes associated with perichondritis and pinna abscess formation are Pseudomonas and Staphylococcus species.² P aeruginosa accounts for a majority (87%) of post-piercing infections of the auricular cartilage.²

Continue to: How to treat

How to treat. The cornerstone of treatment is early detection and antimicrobial coverage with antipseudomonal antibiotics. Ciprofloxacin is the oral antibiotic of choice because of its ability to penetrate the tissue.⁴ Other options include clindamycin and third- or fourth-generation cephalosporins. If the wound becomes abscessed, ­perform (or refer for) early surgical incision and drainage.⁵ A failure to promptly recognize perichondritis or to mistakenly prescribe non-­antipseudomonal antibiotics contributes to increased rates of hospitalization.² Cosmetic deformity is the most common complication of perichondritis. This may require reconstructive surgery.

Otitis externa

Acute otitis externa (AOE; “swimmer’s ear”) is cellulitis of the skin and subdermis of the external ear canal. It is most prevalent in warm, moist climates and almost always associated with acute bacterial infection, most commonly P aeruginosa or S aureus.⁶ There is also an increased association with poor water quality (containing higher bacterial loads). Anything breaching the integrity of the ear canal can potentially predispose to the development of AOE. This includes trauma from cleaning, cerumen removal, scratching due to allergic conditions, and placement of hearing-aid devices.⁶

What you’ll see. Suspect AOE when signs or symptoms of ear canal inflammation have appeared rapidly (generally within 2 days) over the past 3 weeks.⁷ Findings include otalgia, itching, fullness, tragal tenderness, ear canal edema, erythema with or without otorrhea, lymphadenitis, or cellulitis of the pinna or adjacent skin.⁷ AOE must be distinguished from other causes of otalgia and otorrhea, including dermatitis and viral infection.

How to treat. Topical therapy is recommended for the initial treatment of uncomplicated AOE, usually given over 7 days. Multiple topical preparations are available, such as ciprofloxacin 0.2%/hydrocortisone 1.0%; neomycin/polymyxin B/hydrocortisone; ofloxacin 0.3%; or acetic acid 2.0%.⁷ Avoid these agents, though, if you suspect tympanic membrane rupture. Quinolone drops are the only topical antimicrobials approved for middle ear use.⁷

Systemic antibiotics are not recommended for the initial treatment of AOE. Topical agents deliver a much higher concentration of medication than can be achieved systemically. Consider systemic antibiotics if there is extension outside the ear canal, a concern for necrotizing otitis externa (more on this in a bit), or the patient is immunodeficient.⁸

Continue to: Patient (or parent) education...

Patient (or parent) education is important to ensure proper medication administration. The patient should lie down with the affected ear facing up. After the canal is filled with drops, the patient should remain in this position for 3 to 5 minutes. Gently massaging the tragus can augment delivery. Patients should keep the ear canal as dry as possible and avoid inserting objects (eg, hearing aids, ear buds, cotton-tipped applicators) into the canal for the duration of treatment. The delivery of topical antibiotics can be enhanced by wick placement. Prescribe analgesics (typically nonsteroidal anti-inflammatory agents) based on severity of pain.⁷

Have patients abstain from water sports for 7 to 10 days. Showering is acceptable with minimal ear exposure to water; bathing is preferred when possible. If there is no clinical improvement in 48 to 72 hours, ask patients to return for re-evaluation.⁸ Prevention is essential for patients with a history of recurrent otitis externa. Acetic acid solutions create an acidic environment within the canal to help prevent recurrent AOE. Ear plugs and petroleum jelly–soaked cotton plugs prior to water exposure may also help prevent recurrent AOE.

Malignant otitis externa

Malignant, or necrotizing, otitis externa is an aggressive disease form of otitis externa that is most common in individuals with diabetes or other immunodeficiency disorders.⁹ Most cases are due to infection with P aeruginosa.¹⁰ Prior to the availability of effective antibiotics, mortality rates in patients with necrotizing otitis externa were as high as 50%.¹¹

What you’ll see. Patients typically present with severe ear pain, otorrhea, conductive hearing loss, and a feeling of fullness in the external ear canal. Physical examination reveals purulent otorrhea and a swollen, tender ear canal. Exposed bone may be visible, most often on the floor of the canal. The tympanic membrane and middle ear are seldom involved on initial presentation.

The infection often originates at the junction of the bony and cartilaginous portion of the external canal, spreading through the fissures of Santorini to the skull base. If not aggressively treated, the infection spreads medially to the tympanomastoid suture causing intracranial complications—usually a facial nerve neuropathy.

Continue to: Given these clinical findings...

Given these clinical findings, promptly order laboratory studies and imaging to confirm the diagnosis. The erythrocyte sedimentation rate and C-reactive protein level are typically elevated, and either can be used as a marker to follow treatment. Computed tomography (CT) helps to determine the location and extent of disease and is recommended as the initial diagnostic imaging modality for patients with suspected malignant otitis externa.¹²

Magnetic resonance imaging helps define soft-tissue changes, dural enhancement, and involvement of medullary bone, making this the preferred modality to monitor therapeutic response.¹² Technetium bone scanning can also be used for the initial diagnosis (particularly if CT findings are normal and clinical suspicion is high) and for follow-up with treatment.

How to treat. Management involves a team approach with otolaryngology, radiology, neurology, endocrinology, and infectious disease specialists. Long term (6-8 weeks) antipseudomonal antibiotic treatment is typical.

In head-to-head laboratory comparisons, distilled water appears to be the best cerumenolytic.

Let culture results guide the choice of antibiotic. Fluoroquinolone therapy, usually ciprofloxacin, is used most often.¹² Surgical intervention may be required for local debridement and drainage of abscesses. Close follow-up is necessary due to reports of recurrence up to 1 year after treatment. If left untreated, necrotizing otitis externa can lead to osteomyelitis, meningitis, septic thrombosis, cerebral abscess, and death.¹¹

Cerumen impaction

The relatively small diameter of the external auditory canal increases the risk for impaction of cerumen and foreign bodies. Cerumen impaction, in particular, is a common primary care complaint. Cerumen forms when glandular secretions from the outer two-thirds of the ear canal mix with exfoliated skin. It functions as a lubricant for the ear canal and as a barrier against infection, water accumulation, and foreign bodies.¹³

Continue to: What you'll see

What you’ll see. You may encounter cerumen impaction in an asymptomatic patient when it prevents visualization of the external auditory canal or tympanic membrane, or when a patient complains of conductive hearing loss, tinnitus, dizziness, ear pain, itching, and cough.¹³ It is found in 1 in 10 children and 1 in 20 adults.¹³ There is a higher incidence in patients who are elderly, are cognitively impaired, or wear hearing devices or ear plugs.^13,14 Asymptomatic cerumen impaction should not be treated. A recent clinical guideline provides a useful “do and don’t” list for patient education (TABLE).¹³

How to treat. In asymptomatic patients, the presence of cerumen on examination is not an indication for removal. Based on current guidelines,¹³ impacted cerumen can safely be removed from the ear canal of symptomatic patients in several ways:

• Manual removal with cerumen loop/spoon or alligator forceps. This method decreases the risk for infection because it limits moisture exposure. However, it should be performed by a health care provider trained in its use because of the risk for trauma to the ear canal and tympanic membrane.
• Irrigation of the ear using tap water or a 50-50 solution of hydrogen peroxide and water. Irrigation can be achieved with a syringe or jet irrigator using a modified tip. This method also has a risk for trauma to the ear canal and tympanic membrane and should only be performed by appropriately trained health care professionals.
• Use of cerumenolytic agents to soften and thin earwax and promote natural extrusion. Several types of cerumenolytic drops (water-based and oil-based) are available and appear to be equally effective. Water-based solutions contain hydrogen peroxide, docusate sodium, acetic acid, and sodium bicarbonate. Oil-based drops may contain peanut, almond, or olive oils. A thorough allergic history should be performed to avoid using products in patients with nut allergies. In head-to-head laboratory comparisons, distilled water appears to be the best cerumenolytic.¹⁵

Foreign bodies

Foreign bodies in the external auditory canal (typically beads, cotton tips, and insects) are more common in children than adults.¹⁶

What you’ll see. Most foreign bodies are lodged in the bony part of the external auditory canal, and many patients try to remove the object before seeking medical care. Removal requires adequate visualization and skill.¹⁷ Although patients may be asymptomatic, most complain of pain, fullness, decreased hearing, or otorrhea.

How to treat. Directly visible objects can often be removed without referral. Suction, irrigation, forceps, probes, and fine hooks have been used. Insect removal can be facilitated by first flooding the canal with xylocaine, alcohol, or mineral oil. Acetone may be used to dissolve foreign bodies containing Styrofoam or to loosen glues. If the object is a button battery, avoid irrigation to prevent liquefaction tissue necrosis.

Continue to: Complications of foreign body removal...

Insect removal can be facilitated by first flooding the canal with xylocaine, alcohol, or mineral oil.

Complications of foreign body removal include pain, otitis externa, otitis media, and trauma to the ear or tympanic membrane. The likelihood of successful removal of the object decreases and the risk for complications increases with each subsequent attempt.¹⁷ Consult an otolaryngologist if sedation or anesthesia is required, the foreign body is tightly wedged, there is trauma to the ear canal or tympanic membrane, the foreign body has a sharp edge (eg, glass or wire), or removal attempts have been unsuccessful.

Trauma

Sports injuries, motor vehicle accidents, bites, falls, and burns are the primary causes of trauma to the external ear.¹⁸

What you’ll see. Blunt auricular trauma predisposes to infection, necrosis, and scar contracture. One of the most common sequelae is cauliflower ear. Trauma is particularly common with contact sports such as boxing, wrestling, or mixed martial arts. The skin of the auricle attaches directly to the perichondrium. Following blunt or shearing trauma to the auricle, hematomas form within the space between the perichondrium and cartilage of the anterior ear.¹⁹Following hematoma formation, the healing process brings chondrocytes and fibroblasts to the subperichondrial space, promoting fibrocartilage formation. Over time (and with repeated injury), this can lead to a chronic, bulbous deformity known as cauliflower ear.

How to treat. Small hematomas can be managed by aspiration, while larger ones generally require open drainage.²⁰ Newer treatments involving pressure dressings and the use of fibrin glue have been proposed.²⁰ Recommend that athletes participating in contact sports wear appropriate protective headgear to prevent auricular hematoma and cauliflower ear.

Neoplasm

Roughly 5% of all skin cancers involve the ear, most frequently the pinna due to chronic sun exposure.²¹ The most frequently occurring malignancy of the external ear is basal cell carcinoma (BCC), which is responsible for 80% of all nonmelanoma skin cancers.²²

Continue to: What you'll see

What you’ll see. BCC of the ear usually involves the preauricular area and the helix. The risk for BCC is related to exposure to ultraviolet radiation. BCC of the ear is more common in men and can be particularly aggressive, highlighting the importance of prevention and prompt recognition. BCC typically presents as a fleshy papule that is often translucent or “pearly’” and has overlying telangiectasia and a “rolled” border. Central ulceration can occur as well.

How to treat. Usual treatment of BCC is surgical excision. Prevention is critical and centers on sun avoidance or the use of appropriate sunscreens.

If the object in the external auditory canal is a button battery, avoid irrigation to prevent liquefaction tissue necrosis.

In addition to BCC, exposure of the external ear to sunlight and ultraviolet radiation predisposes patients to the development of squamous cell carcinoma (SCC) and melanoma. SCC has a variety of presentations including papules, plaques, and nodules. SCC has a higher metastatic potential than does BCC.

Keloid

Keloids are an abnormal healing response to soft-tissue injury: benign fibrocartilaginous growths that extend beyond the original wound.

What you’ll see. Keloids are more common in dark-skinned individuals and tend to result from burns, surgical incisions, infection, trauma, tattooing, injections, piercings, and arthropod bites. In some cases, they arise spontaneously. Keloids are more common in areas of increased skin tension (chest, shoulders, back), but may occur on the ears—most commonly after piercing or trauma. Keloids present clinically as slow-growing rubbery or firm nodules. The diagnosis is typically based on clinical appearance but can be confirmed by histopathology.

Continue to: How to treat

How to treat. Treatments vary and include observation, excision, intralesional injections, cryotherapy, enzyme therapy, silicone gel application, and irradiation.²³ Recurrence is common; no therapy has been proven to be universally superior or preferred.

Congenital malformations

Atresia

Disruption of embryologic development (failed invagination of the external auditory canal) can lead to a stenotic or absent ear canal (aural atresia). Aural atresia is also often associated with fusion of the incus and malleus. This condition occurs predominantly in males. Unilateral atresia is more common than bilateral atresia, and the right ear is more often involved than the left.²⁴

Microtia

Microtia is the incomplete development of the pinna leading to a small or deformed pinna. Microtia can be unilateral or bilateral. As with atresia, microtia more commonly affects males and, if unilateral, the right side is more often affected than the left. Microtia can occur in isolation but is often associated with genetic syndromes such as Treacher Collins syndrome and craniofacial microsomia (Goldenhar syndrome). When microtia is identified (typically at birth or early infancy), audiologic testing and a thorough physical examination for evidence of associated defects should be performed. Consult with an audiologist, clinical geneticist, or pediatric otolaryngologist.

Pre-auricular pits

Pre-auricular pits (sinuses) are tiny indentations anterior to the helix and superior to the tragus. While pre-auricular pits are more common on the right side, they are bilateral in 25% to 50% of cases.²⁵ Pre-auricular pits occur in up to 1% of white children, 5% of black children, and 10% of Asian children.²⁵ Children with this condition should undergo formal audiologic testing as their risk for hearing loss is higher compared with the general population.²⁶

Directly visible foreign objects can often be removed without referral, but the likelihood of success decreases with each subsequent attempt.

The branchio-oto-renal syndrome (associated with pre-auricular pits and hearing loss) also features structural defects of the ear, renal anomalies and/or nasolacrimal duct stenosis or fistulas. If this syndrome is suspected, renal ultrasound imaging is warranted. Other indications for renal ultrasound in patients with a pre-auricular pit are any dysmorphic feature, a family history of deafness, an auricular malformation, or a maternal history of gestational diabetes.²⁷ Pre-auricular pits do not require surgery unless they drain chronically or become recurrently infected. Complete surgical excision is the treatment of choice in these cases.

CORRESPONDENCE 
Mark Stephens, MD, 1850 Park Avenue, State College, PA 16801; mstephens3@pennstatehealth.psu.edu

Which antibiotics are most useful for infection following ear piercing? When is it safe to attempt removal of a foreign body from the ear canal, and which cerumenolytic agent may be best for ear wax? This review covers common ailments of the outer ear, which are often readily diagnosed given a patient’s history and thorough physical examination. We also address more complicated matters such as deciding when to refer for treatment of suspected malignant otitis externa, and which lab markers to follow when managing it yourself.

A (very) brief review of ear anatomy

Understanding the unique embryology and intricate anatomy of the external ear informs our understanding of predictable infections, growths, and malformations.

The external ear is composed of the external auditory canal and auricle. The external auditory canal has a lateral (external) cartilaginous portion and a medial (internal) bony portion. The auricular structure is complex and formed by the helix, antihelix (crura; scaphoid fossa), tragus, antitragus, conchae, and lobule. The auricle is composed of elastic cartilage covered by skin. The lobule is composed of skin, adipose tissue, and connective tissue.

Embryologically, the auricle, auditory canal, and middle ear form from ectoderm of the first 2 branchial arches during early gestation. The auricle forms from the fusion of soft-tissue swellings (hillocks). Three hillocks arise from the first branchial arch and 3 from the second branchial arch during the fifth and sixth weeks of gestation. Tissues from the second branchial arch comprise the lobule, antihelix, and caudal helix. The cartilage of the tragus forms from the first branchial arch. The ear canal forms from an epithelial invagination of the first branchial arch that also occurs during the fifth week of gestation.¹

Infections

Perichondritis

Inflammation or infection of the connective tissue layer surrounding the auricular cartilage (perichondrium) results in perichondritis. Further extension of infection can lead to an auricular abscess. Both of these conditions can have serious consequences.

What you’ll see. The most common risk factor for perichondritis is the popular practice of cosmetic transcartilaginous piercing.² Piercing of the helix, scapha, or anti-helix (often referred to as “high” ear piercing) causes localized trauma that can strip the adjacent perichondrium, decrease blood supply, create cartilaginous microfractures, and lead to devascularization. Rates of infection as high as 35% have been reported with high-ear piercing.³

Rates of infection as high as 35% have been reported with high-ear piercing.

The most common microbes associated with perichondritis and pinna abscess formation are Pseudomonas and Staphylococcus species.² P aeruginosa accounts for a majority (87%) of post-piercing infections of the auricular cartilage.²

Continue to: How to treat

How to treat. The cornerstone of treatment is early detection and antimicrobial coverage with antipseudomonal antibiotics. Ciprofloxacin is the oral antibiotic of choice because of its ability to penetrate the tissue.⁴ Other options include clindamycin and third- or fourth-generation cephalosporins. If the wound becomes abscessed, ­perform (or refer for) early surgical incision and drainage.⁵ A failure to promptly recognize perichondritis or to mistakenly prescribe non-­antipseudomonal antibiotics contributes to increased rates of hospitalization.² Cosmetic deformity is the most common complication of perichondritis. This may require reconstructive surgery.

Otitis externa

Acute otitis externa (AOE; “swimmer’s ear”) is cellulitis of the skin and subdermis of the external ear canal. It is most prevalent in warm, moist climates and almost always associated with acute bacterial infection, most commonly P aeruginosa or S aureus.⁶ There is also an increased association with poor water quality (containing higher bacterial loads). Anything breaching the integrity of the ear canal can potentially predispose to the development of AOE. This includes trauma from cleaning, cerumen removal, scratching due to allergic conditions, and placement of hearing-aid devices.⁶

What you’ll see. Suspect AOE when signs or symptoms of ear canal inflammation have appeared rapidly (generally within 2 days) over the past 3 weeks.⁷ Findings include otalgia, itching, fullness, tragal tenderness, ear canal edema, erythema with or without otorrhea, lymphadenitis, or cellulitis of the pinna or adjacent skin.⁷ AOE must be distinguished from other causes of otalgia and otorrhea, including dermatitis and viral infection.

How to treat. Topical therapy is recommended for the initial treatment of uncomplicated AOE, usually given over 7 days. Multiple topical preparations are available, such as ciprofloxacin 0.2%/hydrocortisone 1.0%; neomycin/polymyxin B/hydrocortisone; ofloxacin 0.3%; or acetic acid 2.0%.⁷ Avoid these agents, though, if you suspect tympanic membrane rupture. Quinolone drops are the only topical antimicrobials approved for middle ear use.⁷

Systemic antibiotics are not recommended for the initial treatment of AOE. Topical agents deliver a much higher concentration of medication than can be achieved systemically. Consider systemic antibiotics if there is extension outside the ear canal, a concern for necrotizing otitis externa (more on this in a bit), or the patient is immunodeficient.⁸

Continue to: Patient (or parent) education...

Patient (or parent) education is important to ensure proper medication administration. The patient should lie down with the affected ear facing up. After the canal is filled with drops, the patient should remain in this position for 3 to 5 minutes. Gently massaging the tragus can augment delivery. Patients should keep the ear canal as dry as possible and avoid inserting objects (eg, hearing aids, ear buds, cotton-tipped applicators) into the canal for the duration of treatment. The delivery of topical antibiotics can be enhanced by wick placement. Prescribe analgesics (typically nonsteroidal anti-inflammatory agents) based on severity of pain.⁷

Have patients abstain from water sports for 7 to 10 days. Showering is acceptable with minimal ear exposure to water; bathing is preferred when possible. If there is no clinical improvement in 48 to 72 hours, ask patients to return for re-evaluation.⁸ Prevention is essential for patients with a history of recurrent otitis externa. Acetic acid solutions create an acidic environment within the canal to help prevent recurrent AOE. Ear plugs and petroleum jelly–soaked cotton plugs prior to water exposure may also help prevent recurrent AOE.

Malignant otitis externa

Malignant, or necrotizing, otitis externa is an aggressive disease form of otitis externa that is most common in individuals with diabetes or other immunodeficiency disorders.⁹ Most cases are due to infection with P aeruginosa.¹⁰ Prior to the availability of effective antibiotics, mortality rates in patients with necrotizing otitis externa were as high as 50%.¹¹

What you’ll see. Patients typically present with severe ear pain, otorrhea, conductive hearing loss, and a feeling of fullness in the external ear canal. Physical examination reveals purulent otorrhea and a swollen, tender ear canal. Exposed bone may be visible, most often on the floor of the canal. The tympanic membrane and middle ear are seldom involved on initial presentation.

The infection often originates at the junction of the bony and cartilaginous portion of the external canal, spreading through the fissures of Santorini to the skull base. If not aggressively treated, the infection spreads medially to the tympanomastoid suture causing intracranial complications—usually a facial nerve neuropathy.

Continue to: Given these clinical findings...

Given these clinical findings, promptly order laboratory studies and imaging to confirm the diagnosis. The erythrocyte sedimentation rate and C-reactive protein level are typically elevated, and either can be used as a marker to follow treatment. Computed tomography (CT) helps to determine the location and extent of disease and is recommended as the initial diagnostic imaging modality for patients with suspected malignant otitis externa.¹²

Magnetic resonance imaging helps define soft-tissue changes, dural enhancement, and involvement of medullary bone, making this the preferred modality to monitor therapeutic response.¹² Technetium bone scanning can also be used for the initial diagnosis (particularly if CT findings are normal and clinical suspicion is high) and for follow-up with treatment.

How to treat. Management involves a team approach with otolaryngology, radiology, neurology, endocrinology, and infectious disease specialists. Long term (6-8 weeks) antipseudomonal antibiotic treatment is typical.

In head-to-head laboratory comparisons, distilled water appears to be the best cerumenolytic.

Let culture results guide the choice of antibiotic. Fluoroquinolone therapy, usually ciprofloxacin, is used most often.¹² Surgical intervention may be required for local debridement and drainage of abscesses. Close follow-up is necessary due to reports of recurrence up to 1 year after treatment. If left untreated, necrotizing otitis externa can lead to osteomyelitis, meningitis, septic thrombosis, cerebral abscess, and death.¹¹

Cerumen impaction

The relatively small diameter of the external auditory canal increases the risk for impaction of cerumen and foreign bodies. Cerumen impaction, in particular, is a common primary care complaint. Cerumen forms when glandular secretions from the outer two-thirds of the ear canal mix with exfoliated skin. It functions as a lubricant for the ear canal and as a barrier against infection, water accumulation, and foreign bodies.¹³

Continue to: What you'll see

What you’ll see. You may encounter cerumen impaction in an asymptomatic patient when it prevents visualization of the external auditory canal or tympanic membrane, or when a patient complains of conductive hearing loss, tinnitus, dizziness, ear pain, itching, and cough.¹³ It is found in 1 in 10 children and 1 in 20 adults.¹³ There is a higher incidence in patients who are elderly, are cognitively impaired, or wear hearing devices or ear plugs.^13,14 Asymptomatic cerumen impaction should not be treated. A recent clinical guideline provides a useful “do and don’t” list for patient education (TABLE).¹³

How to treat. In asymptomatic patients, the presence of cerumen on examination is not an indication for removal. Based on current guidelines,¹³ impacted cerumen can safely be removed from the ear canal of symptomatic patients in several ways:

• Manual removal with cerumen loop/spoon or alligator forceps. This method decreases the risk for infection because it limits moisture exposure. However, it should be performed by a health care provider trained in its use because of the risk for trauma to the ear canal and tympanic membrane.
• Irrigation of the ear using tap water or a 50-50 solution of hydrogen peroxide and water. Irrigation can be achieved with a syringe or jet irrigator using a modified tip. This method also has a risk for trauma to the ear canal and tympanic membrane and should only be performed by appropriately trained health care professionals.
• Use of cerumenolytic agents to soften and thin earwax and promote natural extrusion. Several types of cerumenolytic drops (water-based and oil-based) are available and appear to be equally effective. Water-based solutions contain hydrogen peroxide, docusate sodium, acetic acid, and sodium bicarbonate. Oil-based drops may contain peanut, almond, or olive oils. A thorough allergic history should be performed to avoid using products in patients with nut allergies. In head-to-head laboratory comparisons, distilled water appears to be the best cerumenolytic.¹⁵

Foreign bodies

Foreign bodies in the external auditory canal (typically beads, cotton tips, and insects) are more common in children than adults.¹⁶

What you’ll see. Most foreign bodies are lodged in the bony part of the external auditory canal, and many patients try to remove the object before seeking medical care. Removal requires adequate visualization and skill.¹⁷ Although patients may be asymptomatic, most complain of pain, fullness, decreased hearing, or otorrhea.

How to treat. Directly visible objects can often be removed without referral. Suction, irrigation, forceps, probes, and fine hooks have been used. Insect removal can be facilitated by first flooding the canal with xylocaine, alcohol, or mineral oil. Acetone may be used to dissolve foreign bodies containing Styrofoam or to loosen glues. If the object is a button battery, avoid irrigation to prevent liquefaction tissue necrosis.

Continue to: Complications of foreign body removal...

Insect removal can be facilitated by first flooding the canal with xylocaine, alcohol, or mineral oil.

Complications of foreign body removal include pain, otitis externa, otitis media, and trauma to the ear or tympanic membrane. The likelihood of successful removal of the object decreases and the risk for complications increases with each subsequent attempt.¹⁷ Consult an otolaryngologist if sedation or anesthesia is required, the foreign body is tightly wedged, there is trauma to the ear canal or tympanic membrane, the foreign body has a sharp edge (eg, glass or wire), or removal attempts have been unsuccessful.

Trauma

Sports injuries, motor vehicle accidents, bites, falls, and burns are the primary causes of trauma to the external ear.¹⁸

What you’ll see. Blunt auricular trauma predisposes to infection, necrosis, and scar contracture. One of the most common sequelae is cauliflower ear. Trauma is particularly common with contact sports such as boxing, wrestling, or mixed martial arts. The skin of the auricle attaches directly to the perichondrium. Following blunt or shearing trauma to the auricle, hematomas form within the space between the perichondrium and cartilage of the anterior ear.¹⁹Following hematoma formation, the healing process brings chondrocytes and fibroblasts to the subperichondrial space, promoting fibrocartilage formation. Over time (and with repeated injury), this can lead to a chronic, bulbous deformity known as cauliflower ear.

How to treat. Small hematomas can be managed by aspiration, while larger ones generally require open drainage.²⁰ Newer treatments involving pressure dressings and the use of fibrin glue have been proposed.²⁰ Recommend that athletes participating in contact sports wear appropriate protective headgear to prevent auricular hematoma and cauliflower ear.

Neoplasm

Roughly 5% of all skin cancers involve the ear, most frequently the pinna due to chronic sun exposure.²¹ The most frequently occurring malignancy of the external ear is basal cell carcinoma (BCC), which is responsible for 80% of all nonmelanoma skin cancers.²²

Continue to: What you'll see

What you’ll see. BCC of the ear usually involves the preauricular area and the helix. The risk for BCC is related to exposure to ultraviolet radiation. BCC of the ear is more common in men and can be particularly aggressive, highlighting the importance of prevention and prompt recognition. BCC typically presents as a fleshy papule that is often translucent or “pearly’” and has overlying telangiectasia and a “rolled” border. Central ulceration can occur as well.

How to treat. Usual treatment of BCC is surgical excision. Prevention is critical and centers on sun avoidance or the use of appropriate sunscreens.

If the object in the external auditory canal is a button battery, avoid irrigation to prevent liquefaction tissue necrosis.

In addition to BCC, exposure of the external ear to sunlight and ultraviolet radiation predisposes patients to the development of squamous cell carcinoma (SCC) and melanoma. SCC has a variety of presentations including papules, plaques, and nodules. SCC has a higher metastatic potential than does BCC.

Keloid

Keloids are an abnormal healing response to soft-tissue injury: benign fibrocartilaginous growths that extend beyond the original wound.

What you’ll see. Keloids are more common in dark-skinned individuals and tend to result from burns, surgical incisions, infection, trauma, tattooing, injections, piercings, and arthropod bites. In some cases, they arise spontaneously. Keloids are more common in areas of increased skin tension (chest, shoulders, back), but may occur on the ears—most commonly after piercing or trauma. Keloids present clinically as slow-growing rubbery or firm nodules. The diagnosis is typically based on clinical appearance but can be confirmed by histopathology.

Continue to: How to treat

How to treat. Treatments vary and include observation, excision, intralesional injections, cryotherapy, enzyme therapy, silicone gel application, and irradiation.²³ Recurrence is common; no therapy has been proven to be universally superior or preferred.

Congenital malformations

Atresia

Disruption of embryologic development (failed invagination of the external auditory canal) can lead to a stenotic or absent ear canal (aural atresia). Aural atresia is also often associated with fusion of the incus and malleus. This condition occurs predominantly in males. Unilateral atresia is more common than bilateral atresia, and the right ear is more often involved than the left.²⁴

Microtia

Microtia is the incomplete development of the pinna leading to a small or deformed pinna. Microtia can be unilateral or bilateral. As with atresia, microtia more commonly affects males and, if unilateral, the right side is more often affected than the left. Microtia can occur in isolation but is often associated with genetic syndromes such as Treacher Collins syndrome and craniofacial microsomia (Goldenhar syndrome). When microtia is identified (typically at birth or early infancy), audiologic testing and a thorough physical examination for evidence of associated defects should be performed. Consult with an audiologist, clinical geneticist, or pediatric otolaryngologist.

Pre-auricular pits

Pre-auricular pits (sinuses) are tiny indentations anterior to the helix and superior to the tragus. While pre-auricular pits are more common on the right side, they are bilateral in 25% to 50% of cases.²⁵ Pre-auricular pits occur in up to 1% of white children, 5% of black children, and 10% of Asian children.²⁵ Children with this condition should undergo formal audiologic testing as their risk for hearing loss is higher compared with the general population.²⁶

Directly visible foreign objects can often be removed without referral, but the likelihood of success decreases with each subsequent attempt.

The branchio-oto-renal syndrome (associated with pre-auricular pits and hearing loss) also features structural defects of the ear, renal anomalies and/or nasolacrimal duct stenosis or fistulas. If this syndrome is suspected, renal ultrasound imaging is warranted. Other indications for renal ultrasound in patients with a pre-auricular pit are any dysmorphic feature, a family history of deafness, an auricular malformation, or a maternal history of gestational diabetes.²⁷ Pre-auricular pits do not require surgery unless they drain chronically or become recurrently infected. Complete surgical excision is the treatment of choice in these cases.

CORRESPONDENCE 
Mark Stephens, MD, 1850 Park Avenue, State College, PA 16801; mstephens3@pennstatehealth.psu.edu

This year, medical media has been dominated by reporting on the devastating COVID-19 pandemic. Many studies and analyses have shown that staying at home, social distancing, quarantining of close contacts, and wearing face masks and face shields are effective ways of preventing spread.

Although initially there were no known effective treatments for severe COVID-19 infection (other than oxygen and ventilator support), we now know that dexamethasone,¹ remdesivir,² and convalescent plasma³ are effective in lessening the severity of illness and perhaps preventing death. That said, we will continue to struggle with COVID-19 for the foreseeable future.

We must continue to tend to the other health care needs of our patients even as we deal with COVID-19.

But other medical illnesses actually predominate in terms of morbidity and mortality, even during this pandemic. For example, although there has been an average of roughly 5600 COVID-19-related deaths per week for the past 4 months,⁴ there are, on average, more than 54,000 deaths per week in the United States from other causes.⁵ This means that we must continue to tend to the other health care needs of our patients even as we deal with COVID-19.

In that light, JFP continues to publish practical, evidence-based clinical reviews designed to keep family physicians and other primary health care clinicians up to date on a variety of topics. For instance, in this issue of JFP, we have articles on:

• Opioid prescribing. Although opioids have risks, they remain potent medications for relief from acute pain, as well as cancer-related pain and chronic pain not sufficiently treated with other medications. Mahvan et al provide expert advice on maximizing benefit and minimizing the risks of opioid prescribing.
• Secondary ischemic stroke prevention. For patients who have suffered a transient ischemic attack or minor stroke, a mainstay of prevention is antiplatelet therapy. Aspirin alone used to be the treatment of choice, but research has demonstrated the value of adding another antiplatelet agent. Helmer et al’s thorough review reminds us that the antiplatelet drug of choice, in addition to aspirin, is clopidogrel, which should be used only for the first 30 days after the event because of an increased bleeding risk.
• Combatting Clostridioides difficile infection. CDI has been a difficult condition to treat, especially in high-risk patients. Zukauckas et al provide a comprehensive review of diagnosis and management. Vancomycin is now the drug of choice, and fecal transplant is highly effective in preventing recurrent CDI.

This diverse range of timely, practical, evidence-based guidance—in addition to coverage of COVID-19 and other rapidly emerging medical news stories—can all be found on our Web site at www.mdedge.com/familymedicine. We remain committed to supplying you with all of the information you need to provide your patients with the very best care—no matter what brings them in to see you.

This year, medical media has been dominated by reporting on the devastating COVID-19 pandemic. Many studies and analyses have shown that staying at home, social distancing, quarantining of close contacts, and wearing face masks and face shields are effective ways of preventing spread.

Although initially there were no known effective treatments for severe COVID-19 infection (other than oxygen and ventilator support), we now know that dexamethasone,¹ remdesivir,² and convalescent plasma³ are effective in lessening the severity of illness and perhaps preventing death. That said, we will continue to struggle with COVID-19 for the foreseeable future.

We must continue to tend to the other health care needs of our patients even as we deal with COVID-19.

But other medical illnesses actually predominate in terms of morbidity and mortality, even during this pandemic. For example, although there has been an average of roughly 5600 COVID-19-related deaths per week for the past 4 months,⁴ there are, on average, more than 54,000 deaths per week in the United States from other causes.⁵ This means that we must continue to tend to the other health care needs of our patients even as we deal with COVID-19.

In that light, JFP continues to publish practical, evidence-based clinical reviews designed to keep family physicians and other primary health care clinicians up to date on a variety of topics. For instance, in this issue of JFP, we have articles on:

• Opioid prescribing. Although opioids have risks, they remain potent medications for relief from acute pain, as well as cancer-related pain and chronic pain not sufficiently treated with other medications. Mahvan et al provide expert advice on maximizing benefit and minimizing the risks of opioid prescribing.
• Secondary ischemic stroke prevention. For patients who have suffered a transient ischemic attack or minor stroke, a mainstay of prevention is antiplatelet therapy. Aspirin alone used to be the treatment of choice, but research has demonstrated the value of adding another antiplatelet agent. Helmer et al’s thorough review reminds us that the antiplatelet drug of choice, in addition to aspirin, is clopidogrel, which should be used only for the first 30 days after the event because of an increased bleeding risk.
• Combatting Clostridioides difficile infection. CDI has been a difficult condition to treat, especially in high-risk patients. Zukauckas et al provide a comprehensive review of diagnosis and management. Vancomycin is now the drug of choice, and fecal transplant is highly effective in preventing recurrent CDI.

This diverse range of timely, practical, evidence-based guidance—in addition to coverage of COVID-19 and other rapidly emerging medical news stories—can all be found on our Web site at www.mdedge.com/familymedicine. We remain committed to supplying you with all of the information you need to provide your patients with the very best care—no matter what brings them in to see you.

This year, medical media has been dominated by reporting on the devastating COVID-19 pandemic. Many studies and analyses have shown that staying at home, social distancing, quarantining of close contacts, and wearing face masks and face shields are effective ways of preventing spread.

Although initially there were no known effective treatments for severe COVID-19 infection (other than oxygen and ventilator support), we now know that dexamethasone,¹ remdesivir,² and convalescent plasma³ are effective in lessening the severity of illness and perhaps preventing death. That said, we will continue to struggle with COVID-19 for the foreseeable future.

We must continue to tend to the other health care needs of our patients even as we deal with COVID-19.

But other medical illnesses actually predominate in terms of morbidity and mortality, even during this pandemic. For example, although there has been an average of roughly 5600 COVID-19-related deaths per week for the past 4 months,⁴ there are, on average, more than 54,000 deaths per week in the United States from other causes.⁵ This means that we must continue to tend to the other health care needs of our patients even as we deal with COVID-19.

In that light, JFP continues to publish practical, evidence-based clinical reviews designed to keep family physicians and other primary health care clinicians up to date on a variety of topics. For instance, in this issue of JFP, we have articles on:

• Opioid prescribing. Although opioids have risks, they remain potent medications for relief from acute pain, as well as cancer-related pain and chronic pain not sufficiently treated with other medications. Mahvan et al provide expert advice on maximizing benefit and minimizing the risks of opioid prescribing.
• Secondary ischemic stroke prevention. For patients who have suffered a transient ischemic attack or minor stroke, a mainstay of prevention is antiplatelet therapy. Aspirin alone used to be the treatment of choice, but research has demonstrated the value of adding another antiplatelet agent. Helmer et al’s thorough review reminds us that the antiplatelet drug of choice, in addition to aspirin, is clopidogrel, which should be used only for the first 30 days after the event because of an increased bleeding risk.
• Combatting Clostridioides difficile infection. CDI has been a difficult condition to treat, especially in high-risk patients. Zukauckas et al provide a comprehensive review of diagnosis and management. Vancomycin is now the drug of choice, and fecal transplant is highly effective in preventing recurrent CDI.

This diverse range of timely, practical, evidence-based guidance—in addition to coverage of COVID-19 and other rapidly emerging medical news stories—can all be found on our Web site at www.mdedge.com/familymedicine. We remain committed to supplying you with all of the information you need to provide your patients with the very best care—no matter what brings them in to see you.

A 32-year-old woman presented to our clinic with left elbow swelling and pain of 6 days’ duration. She’d had a posterior interosseous nerve (PIN) injection (hydrodissection) at another facility 12 days earlier for refractory intersection syndrome.

During nerve hydrodissection, fluid is injected into the area surrounding the nerve in an effort to displace the muscles, tendons, and fascia and thus reduce friction on the nerve. This treatment, often completed with ultrasound guidance, is utilized by patients who want to obtain pain relief without undergoing surgery for nerve entrapment syndromes.

In this case, a combination of 1 mL (40 mg) of methylprednisolone acetate, 1 mL of lidocaine 2%, and 3 mL of normal saline was injected into the supinator muscle belly (proximal dorsal aspect of the forearm) under ultrasound guidance. Six days later, the patient began to experience elbow pain, redness, and swelling. The symptoms progressed within several hours and became so notable that she sought care at an urgent care facility the next morning. At this facility, she was told she had an infection and was prescribed oral levofloxacin 500 mg/d.

The patient presented to our clinic after 4 days of oral levofloxacin with no improvement of symptoms. She denied chills or fever and described her pain as moderate and radiating to her fingers. There was no history of trauma. The patient reported riding her bike more frequently, which had caused the original forearm pain that warranted the PIN injection. There were no other recent changes to activity. Her medical, social, and surgical histories were otherwise unremarkable.

Her vital signs were normal. Physical exam revealed an erythematous and warm left elbow (FIGURE 1). Her left elbow range of motion (extension and flexion) was mildly decreased due to the pain and swelling.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Aspiration of the patient’s olecranon bursa produced 3 mL of cloudy fluid (FIGURE 2). The patient’s painful, swollen, erythematous, warm elbow, cloudy aspirate, and history of preceding PIN hydrodissection were consistent with a diagnosis of septic olecranon bursitis.

PHOTO COURTESY OF MORTEZA KHODAEE, MD, MPH

When septic bursitis is strongly suspected or confirmed, the patient should be started on an antibiotic regimen that covers S aureus.

Septic bursitis usually is caused by bacteria.^1,2 Bursal infection can result from the spread of infection from nearby tissues or direct inoculation from skin trauma. It can also be iatrogenic and occur among healthy individuals.^2,3 Injection anywhere close to the bursa can inoculate enough bacteria to progress to cellulitis first and then septic bursitis. Inflammatory conditions such as gout and rheumatoid arthritis also can cause acute and/or chronic superficial bursitis.^1,2,4

Differentiating between septic and nonseptic bursitis can be challenging on history and physical exam alone, but specific signs and symptoms should warrant concern for infection.^1,2,4,5 Fever is present in up to 75% of septic cases⁵; however, lack of fever does not rule out septic bursitis. Pain, erythema, warmth, and an overlying skin lesion also can indicate infection.⁴ Diagnostic imaging modalities may help distinguish different types of olecranon bursitis, but in most cases, they are not necessary.²

Other joint disorders factor into the differential

The differential diagnosis is broad and includes a variety of joint disorders in addition to septic (and nonseptic) bursitis.^2,3

Septic arthritis is a deeper infection that involves the elbow joint and is considered an orthopedic emergency due to potential joint destruction.

Continue to: A simple joint effusion

A simple joint effusion also arises from the elbow joint, but this diagnosis becomes less likely when the joint aspirate appears cloudy. A simple joint effusion would not produce bacteria on gram stain and culture.

Crystalline inflammatory arthritis (gout, pseudogout) is due to intra-articular precipitation of crystals (uric acid crystals in gout, calcium pyrophosphate crystals in ­pseudogout).

Hematomas would produce gross blood or clot on joint aspiration.

Cellulitis is an infection of the superficial soft tissue (only) and thus, aspiration is not likely to yield fluid.

Diagnosis can be made with culture of fluid

Confirmation of septic olecranon bursitis is best attained by bursal needle aspiration and culture. Aspiration also can evaluate for other causes of elbow swelling. (If septic olecranon bursitis is suspected clinically, empiric antibiotics should be started while awaiting culture results.⁶) White blood cell counts from the aspirate also may be utilized but have a lower sensitivity and specificity for diagnosis.⁷

Continue to: In addition to aiding in diagnosis

In addition to aiding in diagnosis, bursal aspiration for a patient with septic bursitis can improve symptoms and reduce bacterial load.^1-3,8 The use of a compressive bandage after aspiration may help reduce re-accumulation of the bursal fluid.^1-3,8Staphylococcus aureus is responsible for the majority of septic olecranon bursitis cases.^9-11

Tailoring the antibiotic regimen

There is wide variation in the treatment of septic olecranon bursitis due to the lack of strong evidence-based guidelines.^1,2,8,11-13 When septic bursitis is strongly suspected (or confirmed) the patient should be started on an antibiotic regimen that covers S aureus.^1,2 Once culture results and sensitivities return, the antibiotic regimen can be tailored appropriately.

In cases of mild-to-moderate septic olecranon bursitis in an immunocompetent host, the patient can be started on oral antibiotics and monitored closely as an outpatient.^1-3,8 Patients with septic olecranon bursitis who meet the criteria for systemic inflammatory response syndrome or who are immunocompromised should be hospitalized and started on intravenous antibiotics.^1-3 Recommended duration of antibiotic therapy varies but is usually about 10 to 14 days.^1-3,8 In rare cases, surgical intervention with bursectomy may be necessary.^1,2,14

Our patient was given a dose of ceftriaxone 250 mg intramuscularly and was started on oral sulfamethoxazole/trimethoprim 800 mg/160 mg twice daily after aspiration of the bursa. Culture of the bursal fluid grew oxacillin-sensitive S aureus which was sensitive to a variety of antibiotics including levofloxacin and sulfamethoxazole/trimethoprim. Her symptoms gradually improved (FIGURE 3) and resolved after a 14-day course of oral sulfamethoxazole/trimethoprim.

PHOTO COURTESY OF MORTEZA KHODAEE, MD, MPH

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, Department of Family Medicine & Orthopedics, AFW Clinic, 3055 Roslyn St, Denver, CO 80238; morteza. khodaee@cuanschutz.edu

A 32-year-old woman presented to our clinic with left elbow swelling and pain of 6 days’ duration. She’d had a posterior interosseous nerve (PIN) injection (hydrodissection) at another facility 12 days earlier for refractory intersection syndrome.

During nerve hydrodissection, fluid is injected into the area surrounding the nerve in an effort to displace the muscles, tendons, and fascia and thus reduce friction on the nerve. This treatment, often completed with ultrasound guidance, is utilized by patients who want to obtain pain relief without undergoing surgery for nerve entrapment syndromes.

In this case, a combination of 1 mL (40 mg) of methylprednisolone acetate, 1 mL of lidocaine 2%, and 3 mL of normal saline was injected into the supinator muscle belly (proximal dorsal aspect of the forearm) under ultrasound guidance. Six days later, the patient began to experience elbow pain, redness, and swelling. The symptoms progressed within several hours and became so notable that she sought care at an urgent care facility the next morning. At this facility, she was told she had an infection and was prescribed oral levofloxacin 500 mg/d.

The patient presented to our clinic after 4 days of oral levofloxacin with no improvement of symptoms. She denied chills or fever and described her pain as moderate and radiating to her fingers. There was no history of trauma. The patient reported riding her bike more frequently, which had caused the original forearm pain that warranted the PIN injection. There were no other recent changes to activity. Her medical, social, and surgical histories were otherwise unremarkable.

Her vital signs were normal. Physical exam revealed an erythematous and warm left elbow (FIGURE 1). Her left elbow range of motion (extension and flexion) was mildly decreased due to the pain and swelling.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Aspiration of the patient’s olecranon bursa produced 3 mL of cloudy fluid (FIGURE 2). The patient’s painful, swollen, erythematous, warm elbow, cloudy aspirate, and history of preceding PIN hydrodissection were consistent with a diagnosis of septic olecranon bursitis.

PHOTO COURTESY OF MORTEZA KHODAEE, MD, MPH

When septic bursitis is strongly suspected or confirmed, the patient should be started on an antibiotic regimen that covers S aureus.

Septic bursitis usually is caused by bacteria.^1,2 Bursal infection can result from the spread of infection from nearby tissues or direct inoculation from skin trauma. It can also be iatrogenic and occur among healthy individuals.^2,3 Injection anywhere close to the bursa can inoculate enough bacteria to progress to cellulitis first and then septic bursitis. Inflammatory conditions such as gout and rheumatoid arthritis also can cause acute and/or chronic superficial bursitis.^1,2,4

Differentiating between septic and nonseptic bursitis can be challenging on history and physical exam alone, but specific signs and symptoms should warrant concern for infection.^1,2,4,5 Fever is present in up to 75% of septic cases⁵; however, lack of fever does not rule out septic bursitis. Pain, erythema, warmth, and an overlying skin lesion also can indicate infection.⁴ Diagnostic imaging modalities may help distinguish different types of olecranon bursitis, but in most cases, they are not necessary.²

Other joint disorders factor into the differential

The differential diagnosis is broad and includes a variety of joint disorders in addition to septic (and nonseptic) bursitis.^2,3

Septic arthritis is a deeper infection that involves the elbow joint and is considered an orthopedic emergency due to potential joint destruction.

Continue to: A simple joint effusion

A simple joint effusion also arises from the elbow joint, but this diagnosis becomes less likely when the joint aspirate appears cloudy. A simple joint effusion would not produce bacteria on gram stain and culture.

Crystalline inflammatory arthritis (gout, pseudogout) is due to intra-articular precipitation of crystals (uric acid crystals in gout, calcium pyrophosphate crystals in ­pseudogout).

Hematomas would produce gross blood or clot on joint aspiration.

Cellulitis is an infection of the superficial soft tissue (only) and thus, aspiration is not likely to yield fluid.

Diagnosis can be made with culture of fluid

Confirmation of septic olecranon bursitis is best attained by bursal needle aspiration and culture. Aspiration also can evaluate for other causes of elbow swelling. (If septic olecranon bursitis is suspected clinically, empiric antibiotics should be started while awaiting culture results.⁶) White blood cell counts from the aspirate also may be utilized but have a lower sensitivity and specificity for diagnosis.⁷

Continue to: In addition to aiding in diagnosis

In addition to aiding in diagnosis, bursal aspiration for a patient with septic bursitis can improve symptoms and reduce bacterial load.^1-3,8 The use of a compressive bandage after aspiration may help reduce re-accumulation of the bursal fluid.^1-3,8Staphylococcus aureus is responsible for the majority of septic olecranon bursitis cases.^9-11

Tailoring the antibiotic regimen

There is wide variation in the treatment of septic olecranon bursitis due to the lack of strong evidence-based guidelines.^1,2,8,11-13 When septic bursitis is strongly suspected (or confirmed) the patient should be started on an antibiotic regimen that covers S aureus.^1,2 Once culture results and sensitivities return, the antibiotic regimen can be tailored appropriately.

In cases of mild-to-moderate septic olecranon bursitis in an immunocompetent host, the patient can be started on oral antibiotics and monitored closely as an outpatient.^1-3,8 Patients with septic olecranon bursitis who meet the criteria for systemic inflammatory response syndrome or who are immunocompromised should be hospitalized and started on intravenous antibiotics.^1-3 Recommended duration of antibiotic therapy varies but is usually about 10 to 14 days.^1-3,8 In rare cases, surgical intervention with bursectomy may be necessary.^1,2,14

Our patient was given a dose of ceftriaxone 250 mg intramuscularly and was started on oral sulfamethoxazole/trimethoprim 800 mg/160 mg twice daily after aspiration of the bursa. Culture of the bursal fluid grew oxacillin-sensitive S aureus which was sensitive to a variety of antibiotics including levofloxacin and sulfamethoxazole/trimethoprim. Her symptoms gradually improved (FIGURE 3) and resolved after a 14-day course of oral sulfamethoxazole/trimethoprim.

PHOTO COURTESY OF MORTEZA KHODAEE, MD, MPH

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, Department of Family Medicine & Orthopedics, AFW Clinic, 3055 Roslyn St, Denver, CO 80238; morteza. khodaee@cuanschutz.edu

A 32-year-old woman presented to our clinic with left elbow swelling and pain of 6 days’ duration. She’d had a posterior interosseous nerve (PIN) injection (hydrodissection) at another facility 12 days earlier for refractory intersection syndrome.

During nerve hydrodissection, fluid is injected into the area surrounding the nerve in an effort to displace the muscles, tendons, and fascia and thus reduce friction on the nerve. This treatment, often completed with ultrasound guidance, is utilized by patients who want to obtain pain relief without undergoing surgery for nerve entrapment syndromes.

In this case, a combination of 1 mL (40 mg) of methylprednisolone acetate, 1 mL of lidocaine 2%, and 3 mL of normal saline was injected into the supinator muscle belly (proximal dorsal aspect of the forearm) under ultrasound guidance. Six days later, the patient began to experience elbow pain, redness, and swelling. The symptoms progressed within several hours and became so notable that she sought care at an urgent care facility the next morning. At this facility, she was told she had an infection and was prescribed oral levofloxacin 500 mg/d.

The patient presented to our clinic after 4 days of oral levofloxacin with no improvement of symptoms. She denied chills or fever and described her pain as moderate and radiating to her fingers. There was no history of trauma. The patient reported riding her bike more frequently, which had caused the original forearm pain that warranted the PIN injection. There were no other recent changes to activity. Her medical, social, and surgical histories were otherwise unremarkable.

Her vital signs were normal. Physical exam revealed an erythematous and warm left elbow (FIGURE 1). Her left elbow range of motion (extension and flexion) was mildly decreased due to the pain and swelling.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Aspiration of the patient’s olecranon bursa produced 3 mL of cloudy fluid (FIGURE 2). The patient’s painful, swollen, erythematous, warm elbow, cloudy aspirate, and history of preceding PIN hydrodissection were consistent with a diagnosis of septic olecranon bursitis.

PHOTO COURTESY OF MORTEZA KHODAEE, MD, MPH

When septic bursitis is strongly suspected or confirmed, the patient should be started on an antibiotic regimen that covers S aureus.

Septic bursitis usually is caused by bacteria.^1,2 Bursal infection can result from the spread of infection from nearby tissues or direct inoculation from skin trauma. It can also be iatrogenic and occur among healthy individuals.^2,3 Injection anywhere close to the bursa can inoculate enough bacteria to progress to cellulitis first and then septic bursitis. Inflammatory conditions such as gout and rheumatoid arthritis also can cause acute and/or chronic superficial bursitis.^1,2,4

Differentiating between septic and nonseptic bursitis can be challenging on history and physical exam alone, but specific signs and symptoms should warrant concern for infection.^1,2,4,5 Fever is present in up to 75% of septic cases⁵; however, lack of fever does not rule out septic bursitis. Pain, erythema, warmth, and an overlying skin lesion also can indicate infection.⁴ Diagnostic imaging modalities may help distinguish different types of olecranon bursitis, but in most cases, they are not necessary.²

Other joint disorders factor into the differential

The differential diagnosis is broad and includes a variety of joint disorders in addition to septic (and nonseptic) bursitis.^2,3

Septic arthritis is a deeper infection that involves the elbow joint and is considered an orthopedic emergency due to potential joint destruction.

Continue to: A simple joint effusion

A simple joint effusion also arises from the elbow joint, but this diagnosis becomes less likely when the joint aspirate appears cloudy. A simple joint effusion would not produce bacteria on gram stain and culture.

Crystalline inflammatory arthritis (gout, pseudogout) is due to intra-articular precipitation of crystals (uric acid crystals in gout, calcium pyrophosphate crystals in ­pseudogout).

Hematomas would produce gross blood or clot on joint aspiration.

Cellulitis is an infection of the superficial soft tissue (only) and thus, aspiration is not likely to yield fluid.

Diagnosis can be made with culture of fluid

Confirmation of septic olecranon bursitis is best attained by bursal needle aspiration and culture. Aspiration also can evaluate for other causes of elbow swelling. (If septic olecranon bursitis is suspected clinically, empiric antibiotics should be started while awaiting culture results.⁶) White blood cell counts from the aspirate also may be utilized but have a lower sensitivity and specificity for diagnosis.⁷

Continue to: In addition to aiding in diagnosis

In addition to aiding in diagnosis, bursal aspiration for a patient with septic bursitis can improve symptoms and reduce bacterial load.^1-3,8 The use of a compressive bandage after aspiration may help reduce re-accumulation of the bursal fluid.^1-3,8Staphylococcus aureus is responsible for the majority of septic olecranon bursitis cases.^9-11

Tailoring the antibiotic regimen

There is wide variation in the treatment of septic olecranon bursitis due to the lack of strong evidence-based guidelines.^1,2,8,11-13 When septic bursitis is strongly suspected (or confirmed) the patient should be started on an antibiotic regimen that covers S aureus.^1,2 Once culture results and sensitivities return, the antibiotic regimen can be tailored appropriately.

In cases of mild-to-moderate septic olecranon bursitis in an immunocompetent host, the patient can be started on oral antibiotics and monitored closely as an outpatient.^1-3,8 Patients with septic olecranon bursitis who meet the criteria for systemic inflammatory response syndrome or who are immunocompromised should be hospitalized and started on intravenous antibiotics.^1-3 Recommended duration of antibiotic therapy varies but is usually about 10 to 14 days.^1-3,8 In rare cases, surgical intervention with bursectomy may be necessary.^1,2,14

Our patient was given a dose of ceftriaxone 250 mg intramuscularly and was started on oral sulfamethoxazole/trimethoprim 800 mg/160 mg twice daily after aspiration of the bursa. Culture of the bursal fluid grew oxacillin-sensitive S aureus which was sensitive to a variety of antibiotics including levofloxacin and sulfamethoxazole/trimethoprim. Her symptoms gradually improved (FIGURE 3) and resolved after a 14-day course of oral sulfamethoxazole/trimethoprim.

PHOTO COURTESY OF MORTEZA KHODAEE, MD, MPH

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, Department of Family Medicine & Orthopedics, AFW Clinic, 3055 Roslyn St, Denver, CO 80238; morteza. khodaee@cuanschutz.edu