Mixed Topics

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

Self-injurious behaviors are common and can be either volitional or unintentional. Often people who perform these behaviors receive “tongue lashings” from family, friends, and loved ones. We recently treated a patient whose lesion in the oral cavity was thought to be caused by some form of self-injury, though the prognosis clearly depended on the true culprit. It is important for clinicians to identify the cause of the injury when encountering patients with oral cavity lesions.

Case Presentation

A 40-year-old white male with a medical history of bipolar disorder, posttraumatic stress disorder, polysubstance abuse, and recently diagnosed temporomandibular joint (TMJ) syndrome was seen in outpatient primary care for a bleeding lesion in his mouth for the past 3 weeks. The lesion was under the surface of his right tongue. He first noted the lesion after he had burned himself tasting some homemade rice pudding while under the influence of marijuana. The next day, an impression was taken of his mouth by a dental assistant who was fitting him for an oral appliance for his TMJ syndrome; according to his history, she did not perform a visual inspection of his mouth nor could he recall his last dental examination. He had neither lost weight nor experienced dysphagia. He was not taking any prescribed medications, had an 8 pack-year history of smoking cigarettes, and had smoked crack cocaine intermittently for several years. The also patient had chewed one-half tin per day of chewing tobacco for 5 years, though he had quit 7 years before presentation. He was consuming 6 alcoholic drinks daily and had no history of chewing betel nuts.

On physical examination, the patient seemed extremely anxious, but his vital signs were unremarkable. The nasal dorsum was straight, and the nares were widely patent. There were no suspicious cutaneous lesions noted of the face, head, trunk, or extremities. The salivary glands were soft and showed no lesions or masses within the parotid or submandibular glands bilaterally. There was no obvious obstruction of Stenson or Wharton ducts bilaterally. He had normal lips and oral competence. The dentition was noted to be fair.

A nonfriable, 1.5 cm-wide lesion was found on the ventral surface of the right tongue (Figure 1). The tongue was mobile. The mouth floor was soft and without evidence of masses or lesions. The tonsils, tonsillar pillars, palate, and base of tongue did not show any concerning lesions or masses. The neck revealed a nonenlarged thyroid and no lymphadenopathy. The remainder of the examination was unremarkable.

Diagnosis

Given his risk factors of alcohol use disorder and a history of both inhaled and chewing tobacco, oral squamous cell carcinoma (SCC) was considered. The differential diagnosis also included pyogenic granuloma, mucocele, sublingual fibroma, and metastasis to the oral soft tissue. Due to its implications with respect to morbidity and mortality, we thought it necessary to rule out SCC of the oral cavity. SCC comprises more than 90% of oral malignancies, and tobacco-related products, alcohol, and human papilloma virus are well-established risk factors.¹

Pyogenic granuloma, also known as eruptive hemangioma and lobular capillary hemangioma, is a relatively common benign lesion of the skin and mucosal surfaces that often presents as a solitary, rapidly enlarging papule or nodule that is extremely friable.² Interestingly, pyogenic granuloma is a misnomer, since it is neither infectious in origin nor granulomatous when visualized under the microscope and is thought to arise from an exuberant tissue response to localized irritation or trauma. An individual lesion can range in size from a few millimeters to a few centimeters and generally reaches its maximum size within a matter of weeks; they often arise at sites of minor trauma.³ While the pathogenesis of pyogenic granuloma has not been clearly established, it seems to be related to an imbalance of angiogenesis secondary to overexpression of vascular endothelial growth factor and basic fibroblast growth factor.⁴ While they can occur at any age, pyogenic granulomas are frequently seen in pediatric patients and during pregnancy.

A fibroma, also known as an irritation fibroma, is one of the more common fibrous tumorlike growths and is often caused by trauma or irritation. It usually presents as a smooth-surfaced, painless solid lesion, though it can be nodular and histopathologically shows collagen and connective tissue.⁵ While fibromas can occur anywhere in the oral cavity, they commonly arise on the buccal mucosa along the plane of occlusion between the maxillary and mandibular teeth.

Mucoceles are the most common benign lesions in the mouth and are commonly found on the lower lip and are mucus-filled cavities, arising from the accumulation of mucus from trauma or lip-biting and alteration of minor salivary glands.⁶ Our patient’s rapid evolution and history of trauma were consistent with a mucocele. Although the lower lip is the most common site of involvement, mucoceles also occur on the tongue, cheek, palate, and mouth floor.Metastases to the oral cavity are rare and comprise only 1% of all oral cavity malignancies.⁷ Although most commonly seen in the jaw, nearly one-third of oral cavity metastases are in the soft tissue.⁸ They generally occur late in the course of disease, and the time between appearance and death is usually short.⁸ Our patient’s lack of known primary malignancy and lack of weight loss rendered this diagnosis unlikely.

Other possibilities include peripheral giant cell granuloma, a reactive hyperplastic lesion of the oral cavity originating from the periosteum or periodontal membrane following local irritation or chronic trauma,⁹ and peripheral ossifying fibroma, a reactive soft tissue growth usually seen on the interdental papilla.¹⁰

Surgical excision was performed and revealed reactive epidermal hyperplasia, ulceration, granulation tissue formation, and marked inflammation with reactive changes. There was no evidence of malignancy and was interpreted as consistent with pyogenic granuloma (Figures 2 and 3) likely due to the trauma from the thermal burn or poor dentition.

Management

The patient was relieved to be informed of the diagnosis of an unusual presentation of pyogenic granuloma with no evidence of cancer. Current treatment strategies for pyogenic granuloma include surgical excision, shave excision with cautery, cryotherapy, sclerotherapy, carbon dioxide or pulsed dye laser, as well as expectant management. However, recurrence after initial treatment can occur, with lower recurrence rates occurring with surgical excision.¹¹

Although we wouldn’t state that we gave the patient a “tongue-lashing,” we strongly advised him that he return to his dentist and abstain from tobacco products, alcohol, illicit drugs, and taste-testing scalding food directly from the pot.

Self-injurious behaviors are common and can be either volitional or unintentional. Often people who perform these behaviors receive “tongue lashings” from family, friends, and loved ones. We recently treated a patient whose lesion in the oral cavity was thought to be caused by some form of self-injury, though the prognosis clearly depended on the true culprit. It is important for clinicians to identify the cause of the injury when encountering patients with oral cavity lesions.

Case Presentation

A 40-year-old white male with a medical history of bipolar disorder, posttraumatic stress disorder, polysubstance abuse, and recently diagnosed temporomandibular joint (TMJ) syndrome was seen in outpatient primary care for a bleeding lesion in his mouth for the past 3 weeks. The lesion was under the surface of his right tongue. He first noted the lesion after he had burned himself tasting some homemade rice pudding while under the influence of marijuana. The next day, an impression was taken of his mouth by a dental assistant who was fitting him for an oral appliance for his TMJ syndrome; according to his history, she did not perform a visual inspection of his mouth nor could he recall his last dental examination. He had neither lost weight nor experienced dysphagia. He was not taking any prescribed medications, had an 8 pack-year history of smoking cigarettes, and had smoked crack cocaine intermittently for several years. The also patient had chewed one-half tin per day of chewing tobacco for 5 years, though he had quit 7 years before presentation. He was consuming 6 alcoholic drinks daily and had no history of chewing betel nuts.

On physical examination, the patient seemed extremely anxious, but his vital signs were unremarkable. The nasal dorsum was straight, and the nares were widely patent. There were no suspicious cutaneous lesions noted of the face, head, trunk, or extremities. The salivary glands were soft and showed no lesions or masses within the parotid or submandibular glands bilaterally. There was no obvious obstruction of Stenson or Wharton ducts bilaterally. He had normal lips and oral competence. The dentition was noted to be fair.

A nonfriable, 1.5 cm-wide lesion was found on the ventral surface of the right tongue (Figure 1). The tongue was mobile. The mouth floor was soft and without evidence of masses or lesions. The tonsils, tonsillar pillars, palate, and base of tongue did not show any concerning lesions or masses. The neck revealed a nonenlarged thyroid and no lymphadenopathy. The remainder of the examination was unremarkable.

Diagnosis

Given his risk factors of alcohol use disorder and a history of both inhaled and chewing tobacco, oral squamous cell carcinoma (SCC) was considered. The differential diagnosis also included pyogenic granuloma, mucocele, sublingual fibroma, and metastasis to the oral soft tissue. Due to its implications with respect to morbidity and mortality, we thought it necessary to rule out SCC of the oral cavity. SCC comprises more than 90% of oral malignancies, and tobacco-related products, alcohol, and human papilloma virus are well-established risk factors.¹

Pyogenic granuloma, also known as eruptive hemangioma and lobular capillary hemangioma, is a relatively common benign lesion of the skin and mucosal surfaces that often presents as a solitary, rapidly enlarging papule or nodule that is extremely friable.² Interestingly, pyogenic granuloma is a misnomer, since it is neither infectious in origin nor granulomatous when visualized under the microscope and is thought to arise from an exuberant tissue response to localized irritation or trauma. An individual lesion can range in size from a few millimeters to a few centimeters and generally reaches its maximum size within a matter of weeks; they often arise at sites of minor trauma.³ While the pathogenesis of pyogenic granuloma has not been clearly established, it seems to be related to an imbalance of angiogenesis secondary to overexpression of vascular endothelial growth factor and basic fibroblast growth factor.⁴ While they can occur at any age, pyogenic granulomas are frequently seen in pediatric patients and during pregnancy.

A fibroma, also known as an irritation fibroma, is one of the more common fibrous tumorlike growths and is often caused by trauma or irritation. It usually presents as a smooth-surfaced, painless solid lesion, though it can be nodular and histopathologically shows collagen and connective tissue.⁵ While fibromas can occur anywhere in the oral cavity, they commonly arise on the buccal mucosa along the plane of occlusion between the maxillary and mandibular teeth.

Mucoceles are the most common benign lesions in the mouth and are commonly found on the lower lip and are mucus-filled cavities, arising from the accumulation of mucus from trauma or lip-biting and alteration of minor salivary glands.⁶ Our patient’s rapid evolution and history of trauma were consistent with a mucocele. Although the lower lip is the most common site of involvement, mucoceles also occur on the tongue, cheek, palate, and mouth floor.Metastases to the oral cavity are rare and comprise only 1% of all oral cavity malignancies.⁷ Although most commonly seen in the jaw, nearly one-third of oral cavity metastases are in the soft tissue.⁸ They generally occur late in the course of disease, and the time between appearance and death is usually short.⁸ Our patient’s lack of known primary malignancy and lack of weight loss rendered this diagnosis unlikely.

Other possibilities include peripheral giant cell granuloma, a reactive hyperplastic lesion of the oral cavity originating from the periosteum or periodontal membrane following local irritation or chronic trauma,⁹ and peripheral ossifying fibroma, a reactive soft tissue growth usually seen on the interdental papilla.¹⁰

Surgical excision was performed and revealed reactive epidermal hyperplasia, ulceration, granulation tissue formation, and marked inflammation with reactive changes. There was no evidence of malignancy and was interpreted as consistent with pyogenic granuloma (Figures 2 and 3) likely due to the trauma from the thermal burn or poor dentition.

Management

The patient was relieved to be informed of the diagnosis of an unusual presentation of pyogenic granuloma with no evidence of cancer. Current treatment strategies for pyogenic granuloma include surgical excision, shave excision with cautery, cryotherapy, sclerotherapy, carbon dioxide or pulsed dye laser, as well as expectant management. However, recurrence after initial treatment can occur, with lower recurrence rates occurring with surgical excision.¹¹

Although we wouldn’t state that we gave the patient a “tongue-lashing,” we strongly advised him that he return to his dentist and abstain from tobacco products, alcohol, illicit drugs, and taste-testing scalding food directly from the pot.

Self-injurious behaviors are common and can be either volitional or unintentional. Often people who perform these behaviors receive “tongue lashings” from family, friends, and loved ones. We recently treated a patient whose lesion in the oral cavity was thought to be caused by some form of self-injury, though the prognosis clearly depended on the true culprit. It is important for clinicians to identify the cause of the injury when encountering patients with oral cavity lesions.

Case Presentation

A 40-year-old white male with a medical history of bipolar disorder, posttraumatic stress disorder, polysubstance abuse, and recently diagnosed temporomandibular joint (TMJ) syndrome was seen in outpatient primary care for a bleeding lesion in his mouth for the past 3 weeks. The lesion was under the surface of his right tongue. He first noted the lesion after he had burned himself tasting some homemade rice pudding while under the influence of marijuana. The next day, an impression was taken of his mouth by a dental assistant who was fitting him for an oral appliance for his TMJ syndrome; according to his history, she did not perform a visual inspection of his mouth nor could he recall his last dental examination. He had neither lost weight nor experienced dysphagia. He was not taking any prescribed medications, had an 8 pack-year history of smoking cigarettes, and had smoked crack cocaine intermittently for several years. The also patient had chewed one-half tin per day of chewing tobacco for 5 years, though he had quit 7 years before presentation. He was consuming 6 alcoholic drinks daily and had no history of chewing betel nuts.

On physical examination, the patient seemed extremely anxious, but his vital signs were unremarkable. The nasal dorsum was straight, and the nares were widely patent. There were no suspicious cutaneous lesions noted of the face, head, trunk, or extremities. The salivary glands were soft and showed no lesions or masses within the parotid or submandibular glands bilaterally. There was no obvious obstruction of Stenson or Wharton ducts bilaterally. He had normal lips and oral competence. The dentition was noted to be fair.

A nonfriable, 1.5 cm-wide lesion was found on the ventral surface of the right tongue (Figure 1). The tongue was mobile. The mouth floor was soft and without evidence of masses or lesions. The tonsils, tonsillar pillars, palate, and base of tongue did not show any concerning lesions or masses. The neck revealed a nonenlarged thyroid and no lymphadenopathy. The remainder of the examination was unremarkable.

Diagnosis

Given his risk factors of alcohol use disorder and a history of both inhaled and chewing tobacco, oral squamous cell carcinoma (SCC) was considered. The differential diagnosis also included pyogenic granuloma, mucocele, sublingual fibroma, and metastasis to the oral soft tissue. Due to its implications with respect to morbidity and mortality, we thought it necessary to rule out SCC of the oral cavity. SCC comprises more than 90% of oral malignancies, and tobacco-related products, alcohol, and human papilloma virus are well-established risk factors.¹

Pyogenic granuloma, also known as eruptive hemangioma and lobular capillary hemangioma, is a relatively common benign lesion of the skin and mucosal surfaces that often presents as a solitary, rapidly enlarging papule or nodule that is extremely friable.² Interestingly, pyogenic granuloma is a misnomer, since it is neither infectious in origin nor granulomatous when visualized under the microscope and is thought to arise from an exuberant tissue response to localized irritation or trauma. An individual lesion can range in size from a few millimeters to a few centimeters and generally reaches its maximum size within a matter of weeks; they often arise at sites of minor trauma.³ While the pathogenesis of pyogenic granuloma has not been clearly established, it seems to be related to an imbalance of angiogenesis secondary to overexpression of vascular endothelial growth factor and basic fibroblast growth factor.⁴ While they can occur at any age, pyogenic granulomas are frequently seen in pediatric patients and during pregnancy.

A fibroma, also known as an irritation fibroma, is one of the more common fibrous tumorlike growths and is often caused by trauma or irritation. It usually presents as a smooth-surfaced, painless solid lesion, though it can be nodular and histopathologically shows collagen and connective tissue.⁵ While fibromas can occur anywhere in the oral cavity, they commonly arise on the buccal mucosa along the plane of occlusion between the maxillary and mandibular teeth.

Mucoceles are the most common benign lesions in the mouth and are commonly found on the lower lip and are mucus-filled cavities, arising from the accumulation of mucus from trauma or lip-biting and alteration of minor salivary glands.⁶ Our patient’s rapid evolution and history of trauma were consistent with a mucocele. Although the lower lip is the most common site of involvement, mucoceles also occur on the tongue, cheek, palate, and mouth floor.Metastases to the oral cavity are rare and comprise only 1% of all oral cavity malignancies.⁷ Although most commonly seen in the jaw, nearly one-third of oral cavity metastases are in the soft tissue.⁸ They generally occur late in the course of disease, and the time between appearance and death is usually short.⁸ Our patient’s lack of known primary malignancy and lack of weight loss rendered this diagnosis unlikely.

Other possibilities include peripheral giant cell granuloma, a reactive hyperplastic lesion of the oral cavity originating from the periosteum or periodontal membrane following local irritation or chronic trauma,⁹ and peripheral ossifying fibroma, a reactive soft tissue growth usually seen on the interdental papilla.¹⁰

Surgical excision was performed and revealed reactive epidermal hyperplasia, ulceration, granulation tissue formation, and marked inflammation with reactive changes. There was no evidence of malignancy and was interpreted as consistent with pyogenic granuloma (Figures 2 and 3) likely due to the trauma from the thermal burn or poor dentition.

Management

The patient was relieved to be informed of the diagnosis of an unusual presentation of pyogenic granuloma with no evidence of cancer. Current treatment strategies for pyogenic granuloma include surgical excision, shave excision with cautery, cryotherapy, sclerotherapy, carbon dioxide or pulsed dye laser, as well as expectant management. However, recurrence after initial treatment can occur, with lower recurrence rates occurring with surgical excision.¹¹

Although we wouldn’t state that we gave the patient a “tongue-lashing,” we strongly advised him that he return to his dentist and abstain from tobacco products, alcohol, illicit drugs, and taste-testing scalding food directly from the pot.

A 53-year-old male veteran with a history of heavy tobacco and alcohol use presented with abdominal pain, emesis, and no bowel movements for 2 days. He had no history of surgical procedures, malignancies, diverticulitis, inflammatory bowel disease, traveling abroad, parasitic infections, tuberculosis exposure, or hospital admissions for abdominal pain. He reported experiencing no flushing, diarrhea, or cardiac symptoms. His medical history included hypertension, depression, and osteoarthritis. His vital signs were within normal limits.

A physical examination revealed a distended abdomen with mild tenderness. He had no inguinal or ventral hernias. He also had no abnormal skin lesions. A rectal examination did not reveal any masses or blood. His laboratory values were normal. X-ray and computed tomography (CT) scan revealed dilated loops of proximal small bowel, mild wall thickening in a segment of the midileum, and narrowing of the distal small bowel suggestive of a partial small bowel obstruction (Figure 1). A 1-cm nonspecific omental nodule also was seen on the CT scan, but no enlarged lymph nodes or mesenteric calcifications were seen. There was no thickening of the terminal ileum.

The patient underwent an exploratory laparotomy, which revealed no adhesions. In the midileum there was an area of thickened bowel with some nodularity associated with the thickness, but no discrete mass. In the mesentery there were multiple hard, white, calcified nodules, with the majority clustered near the thickened ileal segment. There also was a 1-cm hard, peritoneal mass on the anterior abdominal wall. The segment of thickened ileum, the adjacent mesentery, and the peritoneal nodule were resected.

Pathologic examination of the resected tissue showed immunohistochemical stains that were positive for CD79a, CD10, and BCL-2 and negative for CD23, CD5, and CD3. Nineteen mesenteric lymph nodes were negative for malignancy. The postoperative staging positron emission tomography (PET) scan did not reveal any fluorodeoxyglucose avid masses anywhere else, and bone marrow biopsy showed no infiltration.

• What is your diagnosis?
• How would you treat this patient?
   

   

Diagnosis

Based on the pathologic examination of the resected tissue and immunohistochemical stains, this patient was diagnosed with malignant non-Hodgkin B-cell lymphoma, follicular type, grade 1. PET scan and bone marrow biopsy revealed no other lesions, making this a primary lymphoma of the small intestine. The resected tissue showed negative margins and negative lymph nodes, indicating the full extent of the patient’s tumor was removed. He then underwent nasogastric tube decompression and IV fluid resuscitation. Two days later, he had a large bowel movement, and his abdominal pain resolved. He was provided the treatment options of observation only, radiation therapy, or rituximab treatment. Based on the high risk of enteritis following radiation therapy, the patient elected for observation only, with a repeat scan in 6 months. He also was counseled on alcohol and tobacco cessation. At the 6-month oncology follow-up, the patient showed no evidence of disease recurrence.

Discussion

Small bowel obstruction accounts for about 350,000 hospitalizations annually in the US.¹ The incidence is equal in men and women and can present at any age.^2,3 Patients typically present nonspecifically, with intermittent, colicky abdominal pain, nausea, vomiting, and constipation.² A physical examination may reveal abdominal distention, rigidity, and hypoactive or absent bowel sounds.¹ The 2 most common etiologies of small bowel obstruction are adhesions from prior abdominal surgery (65%) and incarcerated inguinal hernias (10%).¹ However, in a patient presenting with a small bowel obstruction in a surgically naïve abdomen with no hernias, a more detailed history covering current malignancies, past hospital admissions for abdominal pains, pelvic inflammatory disease, diverticulitis, inflammatory bowel disease, and risks for parasite infection must be taken. The differential should include intraluminal causes, including small bowel malignancy, which accounts for 5% of small bowel obstructions,¹ as well as extraluminal causes, including adhesions from diverticulitis, Meckel diverticulum, Ladd bands, and undiagnosed prior appendicitis.

To provide a tissue diagnosis and definitive treatment, surgical exploration was needed for this patient. Exploratory laparotomy revealed an area of thickened ileum and calcified nodules in its mesentery. Pathologic examination of the resected tissue revealed large lymphoid nodules in a follicular pattern with coarse chromatin (Figure 2). Taken together with the immunohistochemical stains, this was consistent with malignant B-cell non-Hodgkin lymphoma, follicular type, grade 1.

Small bowel malignancy accounts for > 5% of all gastrointestinal tumors.⁴ Of these, small bowel neuroendocrine tumors are the most common, followed by adenocarcinomas, lymphomas, and stromal tumors.⁴ Primary follicular lymphoma (PFL) is a B-cell non-Hodgkin lymphoma, and comprises between 3.8% and 11% of gastrointestinal lymphomas, commonly in the duodenum and terminal ileum.⁵

PFL typically occurs in middle-aged females and can be difficult to diagnose, as most patients are asymptomatic or present with unspecified abdominal pain. Many are diagnosed incidentally when endoscopy biopsies are performed for other reasons.^4,5 Histologically, PFL is composed of a mixed population of small (centrocytes) and large (centroblasts) lymphoid cells, with higher proportions of centroblasts corresponding to a higher grade lymphoma.⁶ The classic immunophenotype of PFL shows coexpression of CD79a (or CD20), CD10, and BCL-2; however, in rare cases, low-grade PFL may stain negative for BCL-2 and have diminished staining for CD10 in interfollicular areas.⁷

PFL generally carries a favorable prognosis. Most patients achieving complete disease regression or stable disease following treatment and a low recurrence rate. Treatment can include surgical resection, radiation, rituximab therapy, chemotherapy, or observation.⁸ Patient also should be counseled in alcohol and tobacco cessation to reduce recurrence risk.

Other small bowel malignancies may present as small bowel obstructions as well. Neuroendocrine tumors and adenocarcinomas are both more common than small bowel lymphomas and can present as small bowel obstruction. However, neuroendocrine tumors are derived from serotonin-expressing enterochromaffin cells of the midgut and often present with classic carcinoid syndrome symptoms, including diarrhea, flushing, and right heart fibrosis, which the patient lacked.⁹ Immunohistology of small bowel adenocarcinoma often shows expression of MUC1 or MUC5AC with tumor markers CEA and CA 19-9.¹⁰

Primary intestinal melanoma, another small bowel malignancy, is extremely rare. More commonly, the etiology of intestinal melanoma is cutaneous melanoma that metastasizes to the gastrointestinal tract.¹¹ This patient had no skin lesions to suggest metastatic melanoma. With intestinal melanoma, immunohistochemical evaluation may show S-100, the most sensitive marker for melanoma, or HMB-45, MART-1/Melan-A, tyrosinase, and MITF.¹²

Conclusion

This case is notable because it highlights the importance of examining the cause of small bowel obstruction in a surgically naïve abdomen, as exploration led to the discovery and curative treatment of a primary intestinal malignancy. It also underscores the nonspecific presentation that PFLs of the small intestine can have and the importance of understanding the different histopathology and immunohistochemical profiles of small bowel malignancies.

A 53-year-old male veteran with a history of heavy tobacco and alcohol use presented with abdominal pain, emesis, and no bowel movements for 2 days. He had no history of surgical procedures, malignancies, diverticulitis, inflammatory bowel disease, traveling abroad, parasitic infections, tuberculosis exposure, or hospital admissions for abdominal pain. He reported experiencing no flushing, diarrhea, or cardiac symptoms. His medical history included hypertension, depression, and osteoarthritis. His vital signs were within normal limits.

A physical examination revealed a distended abdomen with mild tenderness. He had no inguinal or ventral hernias. He also had no abnormal skin lesions. A rectal examination did not reveal any masses or blood. His laboratory values were normal. X-ray and computed tomography (CT) scan revealed dilated loops of proximal small bowel, mild wall thickening in a segment of the midileum, and narrowing of the distal small bowel suggestive of a partial small bowel obstruction (Figure 1). A 1-cm nonspecific omental nodule also was seen on the CT scan, but no enlarged lymph nodes or mesenteric calcifications were seen. There was no thickening of the terminal ileum.

The patient underwent an exploratory laparotomy, which revealed no adhesions. In the midileum there was an area of thickened bowel with some nodularity associated with the thickness, but no discrete mass. In the mesentery there were multiple hard, white, calcified nodules, with the majority clustered near the thickened ileal segment. There also was a 1-cm hard, peritoneal mass on the anterior abdominal wall. The segment of thickened ileum, the adjacent mesentery, and the peritoneal nodule were resected.

Pathologic examination of the resected tissue showed immunohistochemical stains that were positive for CD79a, CD10, and BCL-2 and negative for CD23, CD5, and CD3. Nineteen mesenteric lymph nodes were negative for malignancy. The postoperative staging positron emission tomography (PET) scan did not reveal any fluorodeoxyglucose avid masses anywhere else, and bone marrow biopsy showed no infiltration.

• What is your diagnosis?
• How would you treat this patient?
   

   

Diagnosis

Based on the pathologic examination of the resected tissue and immunohistochemical stains, this patient was diagnosed with malignant non-Hodgkin B-cell lymphoma, follicular type, grade 1. PET scan and bone marrow biopsy revealed no other lesions, making this a primary lymphoma of the small intestine. The resected tissue showed negative margins and negative lymph nodes, indicating the full extent of the patient’s tumor was removed. He then underwent nasogastric tube decompression and IV fluid resuscitation. Two days later, he had a large bowel movement, and his abdominal pain resolved. He was provided the treatment options of observation only, radiation therapy, or rituximab treatment. Based on the high risk of enteritis following radiation therapy, the patient elected for observation only, with a repeat scan in 6 months. He also was counseled on alcohol and tobacco cessation. At the 6-month oncology follow-up, the patient showed no evidence of disease recurrence.

Discussion

Small bowel obstruction accounts for about 350,000 hospitalizations annually in the US.¹ The incidence is equal in men and women and can present at any age.^2,3 Patients typically present nonspecifically, with intermittent, colicky abdominal pain, nausea, vomiting, and constipation.² A physical examination may reveal abdominal distention, rigidity, and hypoactive or absent bowel sounds.¹ The 2 most common etiologies of small bowel obstruction are adhesions from prior abdominal surgery (65%) and incarcerated inguinal hernias (10%).¹ However, in a patient presenting with a small bowel obstruction in a surgically naïve abdomen with no hernias, a more detailed history covering current malignancies, past hospital admissions for abdominal pains, pelvic inflammatory disease, diverticulitis, inflammatory bowel disease, and risks for parasite infection must be taken. The differential should include intraluminal causes, including small bowel malignancy, which accounts for 5% of small bowel obstructions,¹ as well as extraluminal causes, including adhesions from diverticulitis, Meckel diverticulum, Ladd bands, and undiagnosed prior appendicitis.

To provide a tissue diagnosis and definitive treatment, surgical exploration was needed for this patient. Exploratory laparotomy revealed an area of thickened ileum and calcified nodules in its mesentery. Pathologic examination of the resected tissue revealed large lymphoid nodules in a follicular pattern with coarse chromatin (Figure 2). Taken together with the immunohistochemical stains, this was consistent with malignant B-cell non-Hodgkin lymphoma, follicular type, grade 1.

Small bowel malignancy accounts for > 5% of all gastrointestinal tumors.⁴ Of these, small bowel neuroendocrine tumors are the most common, followed by adenocarcinomas, lymphomas, and stromal tumors.⁴ Primary follicular lymphoma (PFL) is a B-cell non-Hodgkin lymphoma, and comprises between 3.8% and 11% of gastrointestinal lymphomas, commonly in the duodenum and terminal ileum.⁵

PFL typically occurs in middle-aged females and can be difficult to diagnose, as most patients are asymptomatic or present with unspecified abdominal pain. Many are diagnosed incidentally when endoscopy biopsies are performed for other reasons.^4,5 Histologically, PFL is composed of a mixed population of small (centrocytes) and large (centroblasts) lymphoid cells, with higher proportions of centroblasts corresponding to a higher grade lymphoma.⁶ The classic immunophenotype of PFL shows coexpression of CD79a (or CD20), CD10, and BCL-2; however, in rare cases, low-grade PFL may stain negative for BCL-2 and have diminished staining for CD10 in interfollicular areas.⁷

PFL generally carries a favorable prognosis. Most patients achieving complete disease regression or stable disease following treatment and a low recurrence rate. Treatment can include surgical resection, radiation, rituximab therapy, chemotherapy, or observation.⁸ Patient also should be counseled in alcohol and tobacco cessation to reduce recurrence risk.

Other small bowel malignancies may present as small bowel obstructions as well. Neuroendocrine tumors and adenocarcinomas are both more common than small bowel lymphomas and can present as small bowel obstruction. However, neuroendocrine tumors are derived from serotonin-expressing enterochromaffin cells of the midgut and often present with classic carcinoid syndrome symptoms, including diarrhea, flushing, and right heart fibrosis, which the patient lacked.⁹ Immunohistology of small bowel adenocarcinoma often shows expression of MUC1 or MUC5AC with tumor markers CEA and CA 19-9.¹⁰

Primary intestinal melanoma, another small bowel malignancy, is extremely rare. More commonly, the etiology of intestinal melanoma is cutaneous melanoma that metastasizes to the gastrointestinal tract.¹¹ This patient had no skin lesions to suggest metastatic melanoma. With intestinal melanoma, immunohistochemical evaluation may show S-100, the most sensitive marker for melanoma, or HMB-45, MART-1/Melan-A, tyrosinase, and MITF.¹²

Conclusion

This case is notable because it highlights the importance of examining the cause of small bowel obstruction in a surgically naïve abdomen, as exploration led to the discovery and curative treatment of a primary intestinal malignancy. It also underscores the nonspecific presentation that PFLs of the small intestine can have and the importance of understanding the different histopathology and immunohistochemical profiles of small bowel malignancies.

A 53-year-old male veteran with a history of heavy tobacco and alcohol use presented with abdominal pain, emesis, and no bowel movements for 2 days. He had no history of surgical procedures, malignancies, diverticulitis, inflammatory bowel disease, traveling abroad, parasitic infections, tuberculosis exposure, or hospital admissions for abdominal pain. He reported experiencing no flushing, diarrhea, or cardiac symptoms. His medical history included hypertension, depression, and osteoarthritis. His vital signs were within normal limits.

A physical examination revealed a distended abdomen with mild tenderness. He had no inguinal or ventral hernias. He also had no abnormal skin lesions. A rectal examination did not reveal any masses or blood. His laboratory values were normal. X-ray and computed tomography (CT) scan revealed dilated loops of proximal small bowel, mild wall thickening in a segment of the midileum, and narrowing of the distal small bowel suggestive of a partial small bowel obstruction (Figure 1). A 1-cm nonspecific omental nodule also was seen on the CT scan, but no enlarged lymph nodes or mesenteric calcifications were seen. There was no thickening of the terminal ileum.

The patient underwent an exploratory laparotomy, which revealed no adhesions. In the midileum there was an area of thickened bowel with some nodularity associated with the thickness, but no discrete mass. In the mesentery there were multiple hard, white, calcified nodules, with the majority clustered near the thickened ileal segment. There also was a 1-cm hard, peritoneal mass on the anterior abdominal wall. The segment of thickened ileum, the adjacent mesentery, and the peritoneal nodule were resected.

Pathologic examination of the resected tissue showed immunohistochemical stains that were positive for CD79a, CD10, and BCL-2 and negative for CD23, CD5, and CD3. Nineteen mesenteric lymph nodes were negative for malignancy. The postoperative staging positron emission tomography (PET) scan did not reveal any fluorodeoxyglucose avid masses anywhere else, and bone marrow biopsy showed no infiltration.

• What is your diagnosis?
• How would you treat this patient?
   

   

Diagnosis

Based on the pathologic examination of the resected tissue and immunohistochemical stains, this patient was diagnosed with malignant non-Hodgkin B-cell lymphoma, follicular type, grade 1. PET scan and bone marrow biopsy revealed no other lesions, making this a primary lymphoma of the small intestine. The resected tissue showed negative margins and negative lymph nodes, indicating the full extent of the patient’s tumor was removed. He then underwent nasogastric tube decompression and IV fluid resuscitation. Two days later, he had a large bowel movement, and his abdominal pain resolved. He was provided the treatment options of observation only, radiation therapy, or rituximab treatment. Based on the high risk of enteritis following radiation therapy, the patient elected for observation only, with a repeat scan in 6 months. He also was counseled on alcohol and tobacco cessation. At the 6-month oncology follow-up, the patient showed no evidence of disease recurrence.

Discussion

Small bowel obstruction accounts for about 350,000 hospitalizations annually in the US.¹ The incidence is equal in men and women and can present at any age.^2,3 Patients typically present nonspecifically, with intermittent, colicky abdominal pain, nausea, vomiting, and constipation.² A physical examination may reveal abdominal distention, rigidity, and hypoactive or absent bowel sounds.¹ The 2 most common etiologies of small bowel obstruction are adhesions from prior abdominal surgery (65%) and incarcerated inguinal hernias (10%).¹ However, in a patient presenting with a small bowel obstruction in a surgically naïve abdomen with no hernias, a more detailed history covering current malignancies, past hospital admissions for abdominal pains, pelvic inflammatory disease, diverticulitis, inflammatory bowel disease, and risks for parasite infection must be taken. The differential should include intraluminal causes, including small bowel malignancy, which accounts for 5% of small bowel obstructions,¹ as well as extraluminal causes, including adhesions from diverticulitis, Meckel diverticulum, Ladd bands, and undiagnosed prior appendicitis.

To provide a tissue diagnosis and definitive treatment, surgical exploration was needed for this patient. Exploratory laparotomy revealed an area of thickened ileum and calcified nodules in its mesentery. Pathologic examination of the resected tissue revealed large lymphoid nodules in a follicular pattern with coarse chromatin (Figure 2). Taken together with the immunohistochemical stains, this was consistent with malignant B-cell non-Hodgkin lymphoma, follicular type, grade 1.

Small bowel malignancy accounts for > 5% of all gastrointestinal tumors.⁴ Of these, small bowel neuroendocrine tumors are the most common, followed by adenocarcinomas, lymphomas, and stromal tumors.⁴ Primary follicular lymphoma (PFL) is a B-cell non-Hodgkin lymphoma, and comprises between 3.8% and 11% of gastrointestinal lymphomas, commonly in the duodenum and terminal ileum.⁵

PFL typically occurs in middle-aged females and can be difficult to diagnose, as most patients are asymptomatic or present with unspecified abdominal pain. Many are diagnosed incidentally when endoscopy biopsies are performed for other reasons.^4,5 Histologically, PFL is composed of a mixed population of small (centrocytes) and large (centroblasts) lymphoid cells, with higher proportions of centroblasts corresponding to a higher grade lymphoma.⁶ The classic immunophenotype of PFL shows coexpression of CD79a (or CD20), CD10, and BCL-2; however, in rare cases, low-grade PFL may stain negative for BCL-2 and have diminished staining for CD10 in interfollicular areas.⁷

PFL generally carries a favorable prognosis. Most patients achieving complete disease regression or stable disease following treatment and a low recurrence rate. Treatment can include surgical resection, radiation, rituximab therapy, chemotherapy, or observation.⁸ Patient also should be counseled in alcohol and tobacco cessation to reduce recurrence risk.

Other small bowel malignancies may present as small bowel obstructions as well. Neuroendocrine tumors and adenocarcinomas are both more common than small bowel lymphomas and can present as small bowel obstruction. However, neuroendocrine tumors are derived from serotonin-expressing enterochromaffin cells of the midgut and often present with classic carcinoid syndrome symptoms, including diarrhea, flushing, and right heart fibrosis, which the patient lacked.⁹ Immunohistology of small bowel adenocarcinoma often shows expression of MUC1 or MUC5AC with tumor markers CEA and CA 19-9.¹⁰

Primary intestinal melanoma, another small bowel malignancy, is extremely rare. More commonly, the etiology of intestinal melanoma is cutaneous melanoma that metastasizes to the gastrointestinal tract.¹¹ This patient had no skin lesions to suggest metastatic melanoma. With intestinal melanoma, immunohistochemical evaluation may show S-100, the most sensitive marker for melanoma, or HMB-45, MART-1/Melan-A, tyrosinase, and MITF.¹²

Conclusion

This case is notable because it highlights the importance of examining the cause of small bowel obstruction in a surgically naïve abdomen, as exploration led to the discovery and curative treatment of a primary intestinal malignancy. It also underscores the nonspecific presentation that PFLs of the small intestine can have and the importance of understanding the different histopathology and immunohistochemical profiles of small bowel malignancies.

Benji K. Mathews, MD, SFHM, CLHM, is chief of hospital medicine at Regions Hospital in St. Paul, Minn., and director of point of care ultrasound (POCUS) for hospital medicine at HealthPartners. He is also the course director for the Society of Hospital Medicine’s 2020 Annual Conference (HM20), to be held April 16-18 in San Diego.

Dr. Mathews, an associate professor of medicine at the University of Minnesota, Minneapolis, is recognized by fellow hospitalists as a pioneer in the use of bedside ultrasound. In fact, his Certificate of Leadership in Hospital Medicine (CLHM) was completed with a focus on ultrasound in hospital medicine, and he is a Fellow in Diagnostic Safety through the Society to Improve Diagnosis in Medicine. “While a resident, I took an interest in the field of improving diagnosis and combined it with the 21st-century innovative tool of bedside ultrasound,” he said. “Now, I continue to teach clinicians, educators, and learners.”

In addition to his interest in POCUS and medical education, Dr. Mathews also has a passion for global health, rooted in a commitment to reducing health care disparities both locally and globally. He has worked with medical missions, nongovernmental organizations, and orphanages in Nepal, India, Bolivia, Honduras, and Costa Rica. This led him to complete the global health course at the University of Minnesota.

Dr. Mathews spent a few minutes with The Hospitalist to discuss his background and his new role of course director of the HM20 Annual Conference.

Can you describe your journey to becoming a hospitalist?

I’ve been a hospitalist for most of the last decade. I was fortunate to be a part of a great residency program at the University of Minnesota Medical School, which started a hospital medicine pathway that had several nationally recognized hospital medicine leaders as mentors. I was lucky to work with several of them through the HealthPartners organization in Saint Paul, and that developed in me a further desire to practice hospital medicine. The group and mentors provided opportunities to develop further niches in my practice, like bedside ultrasound.

How did you first get involved with SHM?

I entered SHM through the influence of mentors at HealthPartners, especially Burke Kealey, MD, SFHM, senior medical director for hospital specialties at HealthPartners Medical Group in Bloomington, Minn. and a past president of the Society, who encouraged me to participate on SHM committees. I eventually applied for the Annual Conference Committee, and somehow was accepted.

At that time, I was a community hospitalist among a lot of academic hospitalists. I thought that my voice could probably diversify the conversation, and bring the perspective of an early-career hospitalist to the discussion around educational offerings at the Annual Conference. I benefited from good mentorship on that committee, and with that experience I started getting involved with our local chapter in Minnesota. That was very important. I became our local chapter president and was able to combine my efforts with SHM nationally with our regional initiatives.

You have a particular interest in point-of-care ultrasound for hospitalists. How did that make its way into your involvement with SHM?

Point-of-care ultrasound and diagnostic error work really took off when I was a resident. My interest in that funneled naturally into the base curriculum of the Annual Conference, where once a year I could come together with 18 of my best hospitalist friends from across the nation to discuss curriculum. We talk about what content is applicable for frontline clinicians, what is right for early learners, and what innovations are coming in the future. Toward that last point, I was always involved as a judge or volunteer for the Research, Innovations and Clinical Vignettes – or RIV – competition at the Annual Conference. That’s the scientific abstract and poster competition at the conference. My interest grew to a point at which I decided to apply for one of the leadership roles in the RIV. I had the opportunity to serve as an Innovations Lead at RIV one year, and then chaired the overall RIV competition. Those opportunities helped me better understand the cutting-edge research that hospitalists should be aware of and which researchers and clinicians we should be in conversation with.

All these roles together have led me to my service as HM20 course director. I see myself as a lucky guy who has benefited from great mentorship, and I want to take advantage of my opportunities to serve.

We’ve been told that your elementary school–age children have learned to use ultrasound!

Well, they’ve learned how to use handheld ultrasound devices on each other. They’re able to find their siblings’ kidneys and hearts. I often show an image of this to encourage hospitalists that, if children can pick it up, highly educated providers can do the same and more.

To register for the Society of Hospital Medicine’s 2020 Annual Conference, please visit the HM20 Registration page.




 

Benji K. Mathews, MD, SFHM, CLHM, is chief of hospital medicine at Regions Hospital in St. Paul, Minn., and director of point of care ultrasound (POCUS) for hospital medicine at HealthPartners. He is also the course director for the Society of Hospital Medicine’s 2020 Annual Conference (HM20), to be held April 16-18 in San Diego.

Dr. Mathews, an associate professor of medicine at the University of Minnesota, Minneapolis, is recognized by fellow hospitalists as a pioneer in the use of bedside ultrasound. In fact, his Certificate of Leadership in Hospital Medicine (CLHM) was completed with a focus on ultrasound in hospital medicine, and he is a Fellow in Diagnostic Safety through the Society to Improve Diagnosis in Medicine. “While a resident, I took an interest in the field of improving diagnosis and combined it with the 21st-century innovative tool of bedside ultrasound,” he said. “Now, I continue to teach clinicians, educators, and learners.”

In addition to his interest in POCUS and medical education, Dr. Mathews also has a passion for global health, rooted in a commitment to reducing health care disparities both locally and globally. He has worked with medical missions, nongovernmental organizations, and orphanages in Nepal, India, Bolivia, Honduras, and Costa Rica. This led him to complete the global health course at the University of Minnesota.

Dr. Mathews spent a few minutes with The Hospitalist to discuss his background and his new role of course director of the HM20 Annual Conference.

Can you describe your journey to becoming a hospitalist?

I’ve been a hospitalist for most of the last decade. I was fortunate to be a part of a great residency program at the University of Minnesota Medical School, which started a hospital medicine pathway that had several nationally recognized hospital medicine leaders as mentors. I was lucky to work with several of them through the HealthPartners organization in Saint Paul, and that developed in me a further desire to practice hospital medicine. The group and mentors provided opportunities to develop further niches in my practice, like bedside ultrasound.

How did you first get involved with SHM?

I entered SHM through the influence of mentors at HealthPartners, especially Burke Kealey, MD, SFHM, senior medical director for hospital specialties at HealthPartners Medical Group in Bloomington, Minn. and a past president of the Society, who encouraged me to participate on SHM committees. I eventually applied for the Annual Conference Committee, and somehow was accepted.

At that time, I was a community hospitalist among a lot of academic hospitalists. I thought that my voice could probably diversify the conversation, and bring the perspective of an early-career hospitalist to the discussion around educational offerings at the Annual Conference. I benefited from good mentorship on that committee, and with that experience I started getting involved with our local chapter in Minnesota. That was very important. I became our local chapter president and was able to combine my efforts with SHM nationally with our regional initiatives.

You have a particular interest in point-of-care ultrasound for hospitalists. How did that make its way into your involvement with SHM?

Point-of-care ultrasound and diagnostic error work really took off when I was a resident. My interest in that funneled naturally into the base curriculum of the Annual Conference, where once a year I could come together with 18 of my best hospitalist friends from across the nation to discuss curriculum. We talk about what content is applicable for frontline clinicians, what is right for early learners, and what innovations are coming in the future. Toward that last point, I was always involved as a judge or volunteer for the Research, Innovations and Clinical Vignettes – or RIV – competition at the Annual Conference. That’s the scientific abstract and poster competition at the conference. My interest grew to a point at which I decided to apply for one of the leadership roles in the RIV. I had the opportunity to serve as an Innovations Lead at RIV one year, and then chaired the overall RIV competition. Those opportunities helped me better understand the cutting-edge research that hospitalists should be aware of and which researchers and clinicians we should be in conversation with.

All these roles together have led me to my service as HM20 course director. I see myself as a lucky guy who has benefited from great mentorship, and I want to take advantage of my opportunities to serve.

We’ve been told that your elementary school–age children have learned to use ultrasound!

Well, they’ve learned how to use handheld ultrasound devices on each other. They’re able to find their siblings’ kidneys and hearts. I often show an image of this to encourage hospitalists that, if children can pick it up, highly educated providers can do the same and more.

To register for the Society of Hospital Medicine’s 2020 Annual Conference, please visit the HM20 Registration page.




 

Benji K. Mathews, MD, SFHM, CLHM, is chief of hospital medicine at Regions Hospital in St. Paul, Minn., and director of point of care ultrasound (POCUS) for hospital medicine at HealthPartners. He is also the course director for the Society of Hospital Medicine’s 2020 Annual Conference (HM20), to be held April 16-18 in San Diego.

Dr. Mathews, an associate professor of medicine at the University of Minnesota, Minneapolis, is recognized by fellow hospitalists as a pioneer in the use of bedside ultrasound. In fact, his Certificate of Leadership in Hospital Medicine (CLHM) was completed with a focus on ultrasound in hospital medicine, and he is a Fellow in Diagnostic Safety through the Society to Improve Diagnosis in Medicine. “While a resident, I took an interest in the field of improving diagnosis and combined it with the 21st-century innovative tool of bedside ultrasound,” he said. “Now, I continue to teach clinicians, educators, and learners.”

In addition to his interest in POCUS and medical education, Dr. Mathews also has a passion for global health, rooted in a commitment to reducing health care disparities both locally and globally. He has worked with medical missions, nongovernmental organizations, and orphanages in Nepal, India, Bolivia, Honduras, and Costa Rica. This led him to complete the global health course at the University of Minnesota.

Dr. Mathews spent a few minutes with The Hospitalist to discuss his background and his new role of course director of the HM20 Annual Conference.

Can you describe your journey to becoming a hospitalist?

I’ve been a hospitalist for most of the last decade. I was fortunate to be a part of a great residency program at the University of Minnesota Medical School, which started a hospital medicine pathway that had several nationally recognized hospital medicine leaders as mentors. I was lucky to work with several of them through the HealthPartners organization in Saint Paul, and that developed in me a further desire to practice hospital medicine. The group and mentors provided opportunities to develop further niches in my practice, like bedside ultrasound.

How did you first get involved with SHM?

I entered SHM through the influence of mentors at HealthPartners, especially Burke Kealey, MD, SFHM, senior medical director for hospital specialties at HealthPartners Medical Group in Bloomington, Minn. and a past president of the Society, who encouraged me to participate on SHM committees. I eventually applied for the Annual Conference Committee, and somehow was accepted.

At that time, I was a community hospitalist among a lot of academic hospitalists. I thought that my voice could probably diversify the conversation, and bring the perspective of an early-career hospitalist to the discussion around educational offerings at the Annual Conference. I benefited from good mentorship on that committee, and with that experience I started getting involved with our local chapter in Minnesota. That was very important. I became our local chapter president and was able to combine my efforts with SHM nationally with our regional initiatives.

You have a particular interest in point-of-care ultrasound for hospitalists. How did that make its way into your involvement with SHM?

Point-of-care ultrasound and diagnostic error work really took off when I was a resident. My interest in that funneled naturally into the base curriculum of the Annual Conference, where once a year I could come together with 18 of my best hospitalist friends from across the nation to discuss curriculum. We talk about what content is applicable for frontline clinicians, what is right for early learners, and what innovations are coming in the future. Toward that last point, I was always involved as a judge or volunteer for the Research, Innovations and Clinical Vignettes – or RIV – competition at the Annual Conference. That’s the scientific abstract and poster competition at the conference. My interest grew to a point at which I decided to apply for one of the leadership roles in the RIV. I had the opportunity to serve as an Innovations Lead at RIV one year, and then chaired the overall RIV competition. Those opportunities helped me better understand the cutting-edge research that hospitalists should be aware of and which researchers and clinicians we should be in conversation with.

All these roles together have led me to my service as HM20 course director. I see myself as a lucky guy who has benefited from great mentorship, and I want to take advantage of my opportunities to serve.

We’ve been told that your elementary school–age children have learned to use ultrasound!

Well, they’ve learned how to use handheld ultrasound devices on each other. They’re able to find their siblings’ kidneys and hearts. I often show an image of this to encourage hospitalists that, if children can pick it up, highly educated providers can do the same and more.

To register for the Society of Hospital Medicine’s 2020 Annual Conference, please visit the HM20 Registration page.




 

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.¹ Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.² Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.³ Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.⁴ Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.⁵

• It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
• Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.¹ Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.² Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.³ Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.⁴ Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.⁵

• It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
• Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

A 59-year-old man is admitted with abdominal pain. He has a history of pancreatitis. A contrast CT scan is ordered. He reports a history of severe shellfish allergy when the radiology tech checks him in for the procedure. You are paged regarding what to do:

A) Continue with scan as ordered.

B) Switch to MRI scan.

C) Switch to MRI scan with gadolinium.

D) Continue with CT with contrast, give dose of Solu-Medrol.

E) Continue with CT with contrast give IV diphenhydramine.
 

The correct answer here is A, This patient can receive his scan and receive contrast as ordered.

For many years, patients have been asked about shellfish allergy as a proxy for having increased risk when receiving iodine containing contrast. The mistaken thought was that shellfish contains iodine, so allergy to shellfish was likely to portend allergy to iodine.

Allergy to shellfish is caused by individual proteins that are definitely not in iodine-containing contrast.¹ Beaty et al. studied the prevalence of the belief that allergy to shellfish is tied to iodine allergy in a survey given to 231 faculty radiologists and interventional cardiologists.² Almost 70% responded that they inquire about seafood allergy before procedures that require iodine contrast, and 37% reported they would withhold the contrast or premedicate patients if they had a seafood allergy.

In a more recent study, Westermann-Clark and colleagues surveyed 252 health professionals before and after an educational intervention to dispel the myth of shellfish allergy and iodinated contrast reactions.³ Before the intervention, 66% of participants felt it was important to ask about shellfish allergies and 93% felt it was important to ask about iodine allergies; 26% responded that they would withhold iodinated contrast material in patients with a shellfish allergy, and 56% would withhold in patients with an iodine allergy. A total of 62% reported they would premedicate patients with a shellfish allergy and 75% would premedicate patients with an iodine allergy. The numbers declined dramatically after the educational intervention.

Patients who have seafood allergy have a higher rate of reactions to iodinated contrast, but not at a higher rate than do patients with other food allergies or asthma.⁴ Most radiology departments do not screen for other food allergies despite the fact these allergies have the same increased risk as for patients with a seafood/shellfish allergy. These patients are more allergic, and in general, are more likely to have reactions. The American Academy of Allergy, Asthma, and Immunology recommends not routinely ordering low- or iso-osmolar radiocontrast media or pretreating with either antihistamines or steroids in patients with a history of seafood allergy.⁵

• It is unnecessary and unhelpful to ask patients about seafood allergies before ordering radiologic studies involving contrast.
• Iodine allergy does not exist.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Narayan AK et al. Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. J Hosp Med. 2016 Jun;11(6):435-7.

2. Beaty AD et al. Seafood allergy and radiocontrast media: Are physicians propagating a myth? Am J Med. 2008 Feb;121(2):158.e1-4.

3. Westermann-Clark E et al. Debunking myths about “allergy” to radiocontrast media in an academic institution. Postgrad Med. 2015 Apr;127(3):295-300.

4. Coakley FV and DM Panicek. Iodine allergy: An oyster without a pearl? AJR Am J Roentgenol. 1997 Oct;169(4):951-2.

5. American Academy of Allergy, Asthma & Immunology recommendations on low- or iso-osmolar radiocontrast media.

6. Schabelman E and M Witting. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-7.

7. van Ketel WG and WH van den Berg. Sensitization to povidone-iodine. Dermatol Clin. 1990 Jan;8(1):107-9.

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.

“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.

The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.

“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.

M. Alexander Otto/MDedge News

“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”

The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.

Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.

The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.

A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).

The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).

The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.

The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.

The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”

In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”

The mechanism for the association is unknown, the authors said.

The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
 

[email protected]

SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.

MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.

“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.

The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.

“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.

M. Alexander Otto/MDedge News

“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”

The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.

Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.

The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.

A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).

The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).

The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.

The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.

The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”

In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”

The mechanism for the association is unknown, the authors said.

The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
 

[email protected]

SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.

MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.

“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.

The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.

“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.

M. Alexander Otto/MDedge News

“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”

The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.

Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.

The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.

A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).

The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).

The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.

The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.

The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”

In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”

The mechanism for the association is unknown, the authors said.

The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
 

[email protected]

SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.

LAS VEGAS – Between 2010 and 2017, the proportion of newly diagnosed cases of acute hepatitis C virus infection rose threefold, driven largely by the concomitant opioid epidemic.

Doug Brunk/MDedge News

That makes efforts to screen, diagnose, and cure high-risk populations more important than ever, Stevan A. Gonzalez, MD, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.

About 70% of HCV cases are related to injection drug use,” said Dr. Gonzalez, medical director of liver transplantation at the Baylor Simmons Transplant Institute at the Baylor Scott & White All Saints Medical Center in Fort Worth, Tex. “This is affecting whites as much as blacks and Hispanics, females as much as males, and in nonurban areas as much as in urban areas.”

Data from the Centers for Disease Control and Prevention and the Substance Abuse and Mental Health Services Administration indicate that during 2004-2014, the number of acute HCV cases among those aged 18-29 years increased 400%, and the use of injection opioids rose 600%.

At the same time, the number of HCV cases among those aged 30-39 years increased 325%, and the use of injection opioids rose 83%.

“We’re starting to see a pattern overlapping between HCV exposure and opioid injection,” Dr. Gonzalez said. Other high-risk populations include homeless and incarcerated individuals.

More than 70 million people worldwide have chronic HCV infection, Dr. Gonzalez noted, with possibly as many as 5 million cases in the United States. It remains the nation’s most common blood-borne infection.

Chronic disease develops in up to 85% of people who are exposed, infection is asymptomatic, and HCV remains one of the leading indications for liver transplantation and causes of liver cancer.

From a geographic standpoint, the prevalence of HCV in young adults is eclipsing that of Baby Boomers in several states in the Appalachian region and in Northeast, which have long been trouble spots for opioid use disorder (Gastroenterol. 2018 May;154[6]:1850-1).

Surprising exposure risk

The primary risk of transmission is through contaminated blood and the exposure through needles.

“It really doesn’t matter whether it’s a needle that has a small amount of dead space where a little bit of blood can remain or needles that have a larger amount of blood,” Dr. Gonzalez said.

“I’ve had patients who come to me and say, ‘I can’t believe I have HCV. It’s impossible. I always use my own needles. They’re always brand new; I’ve never shared with anybody,’” he continued.

“This is where education and awareness is so critical, because it’s not just the needles,” Dr. Gonzalez explained. “HCV can survive on inanimate objects. For example, on a tabletop surface or a water container, HCV can remain viable up to 3 weeks. In a syringe, 2 months. For that reason, HCV can also be transmitted through crack pipes and nasal drug use, where the prevalence can be up to 35%.”

The duration of a person’s HCV infection drives the transmission.

“That’s important to think about, because people who have chronic hepatitis C are infectious until they’re treated,” Dr. Gonzalez said. “If they don’t know that they have hepatitis C, they continue to transmit the virus to others.”

One study found that half of people living with HCV are unaware of their infection (PLoS One. 2014 Jul 2;9[7]:e101554). According to Dr. Gonzalez, forthcoming guidelines from the U.S. Preventive Services Task Force are expected to recommend a one-time screening for HCV infection in all adults aged 18-79 years, a Grade B recommendation. “That’s a big deal,” he said. (The draft recommendations are available here.)

HCV infection disproportionately affects individuals in correctional institutions. In fact, an estimated one in three inmates in the United States has chronic HCV.

“This is sort of a forgotten population with a lot of substance use and mental illness,” Dr. Gonzalez said. “Injection drug use in that setting is the most common risk factor: It’s about 60% in terms of the risk of transmission within correctional settings. HCV-associated liver disease has now surpassed HIV as a cause of death within correctional settings.”
 

Weighing treatment options

The most common oral regimens for chronic HCV include sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. They achieve cure in 93%-100% of cases.

“HCV can be cured; it can be eradicated from the body long term,” Dr. Gonzalez said. “The choice of regimen, treatment duration, and use of ribavirin depends on the presence/absence of cirrhosis, prior treatment experience, and the genotype.”

All six forms of the HCV genotype can be treated with oral medication, he added, and methadone, bupropion, and naloxone are safe to use during therapy.

Reinfection following HCV treatment occurs infrequently. Dr. Gonzalez cited a randomized, controlled trial presented as an abstract at the 2018 annual meeting of the American Association for the Study of Liver Diseases. That study’s researchers found that – among 199 patients on opioid-replacement therapy who were receiving direct-acting antiviral therapy, in whom greater than 50% were actively using drugs – the rate of reinfection at 3 years was 1.8 reinfections/100 person-years.

“That’s lower than people expect,” Dr. Gonzalez said.
 

How to boost screening

Electronic health record systems can be used as an important tool to increase HCV screening in health care settings.

In 2017, researchers published an analysis of three randomized trials carried out at three separate primary care settings to improve screening for HCV: repeated mailings, an EHR best practice alert (BPA), and patient solicitation (Hepatology 2017 Jan;65[1]:44-53). They evaluated HCV antibody testing, diagnosis, and costs for each of the interventions, compared with standard-of-care testing.

The investigators found that the BPA intervention had the lowest incremental cost per completed test – $24 with fixed start-up costs, including technical design and development of the BPA system; $3 without fixed start-up costs. The BPA intervention also had the lowest incremental cost per new case identified.

Other efforts to expand access to screening and treatment are underway.

In 2019, Louisiana health officials negotiated a one-time fee for unlimited access for 5 years to sofosbuvir/velpatasvir (Epclusa) to treat the estimated 30,000 patients on Louisiana Medicaid and in that state’s department of corrections who have HCV.

“The goal is 90% cure; the burden is on the state health department to screen, diagnose, and dispense medication,” Dr. Gonzalez said.

Also in 2019, the state of Washington used an open bidding process to negotiate access to glecaprevir/pibrentasvir (Mavyret) for the state’s Medicaid population who have HCV.

“Those states are setting the pace,” Dr. Gonzalez said. “They are showing examples of how we can start implementing a process to treat these vulnerable populations.”

Meanwhile, the World Health Organization set a goal of eliminating viral hepatitis as a major public health threat by 2030.

“That sounds ambitious, but I think it’s possible,” Dr. Gonzalez said. “It’s important to address these high-risk populations: the incarcerated, people who use drugs, and the homeless, because those are the groups that have a high prevalence of HCV – mainly through injection drug use.

“If we don’t address that population, and we only target the general population, we’re going to have a continual source of transmission,” Dr. Gonzalez warned. “In that case, we would never be able to achieve elimination.”

Dr. Gonzalez disclosed that he is a member of the speakers bureau for AbbVie and Salix.

[email protected]

LAS VEGAS – Between 2010 and 2017, the proportion of newly diagnosed cases of acute hepatitis C virus infection rose threefold, driven largely by the concomitant opioid epidemic.

Doug Brunk/MDedge News

That makes efforts to screen, diagnose, and cure high-risk populations more important than ever, Stevan A. Gonzalez, MD, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.

About 70% of HCV cases are related to injection drug use,” said Dr. Gonzalez, medical director of liver transplantation at the Baylor Simmons Transplant Institute at the Baylor Scott & White All Saints Medical Center in Fort Worth, Tex. “This is affecting whites as much as blacks and Hispanics, females as much as males, and in nonurban areas as much as in urban areas.”

Data from the Centers for Disease Control and Prevention and the Substance Abuse and Mental Health Services Administration indicate that during 2004-2014, the number of acute HCV cases among those aged 18-29 years increased 400%, and the use of injection opioids rose 600%.

At the same time, the number of HCV cases among those aged 30-39 years increased 325%, and the use of injection opioids rose 83%.

“We’re starting to see a pattern overlapping between HCV exposure and opioid injection,” Dr. Gonzalez said. Other high-risk populations include homeless and incarcerated individuals.

More than 70 million people worldwide have chronic HCV infection, Dr. Gonzalez noted, with possibly as many as 5 million cases in the United States. It remains the nation’s most common blood-borne infection.

Chronic disease develops in up to 85% of people who are exposed, infection is asymptomatic, and HCV remains one of the leading indications for liver transplantation and causes of liver cancer.

From a geographic standpoint, the prevalence of HCV in young adults is eclipsing that of Baby Boomers in several states in the Appalachian region and in Northeast, which have long been trouble spots for opioid use disorder (Gastroenterol. 2018 May;154[6]:1850-1).

Surprising exposure risk

The primary risk of transmission is through contaminated blood and the exposure through needles.

“It really doesn’t matter whether it’s a needle that has a small amount of dead space where a little bit of blood can remain or needles that have a larger amount of blood,” Dr. Gonzalez said.

“I’ve had patients who come to me and say, ‘I can’t believe I have HCV. It’s impossible. I always use my own needles. They’re always brand new; I’ve never shared with anybody,’” he continued.

“This is where education and awareness is so critical, because it’s not just the needles,” Dr. Gonzalez explained. “HCV can survive on inanimate objects. For example, on a tabletop surface or a water container, HCV can remain viable up to 3 weeks. In a syringe, 2 months. For that reason, HCV can also be transmitted through crack pipes and nasal drug use, where the prevalence can be up to 35%.”

The duration of a person’s HCV infection drives the transmission.

“That’s important to think about, because people who have chronic hepatitis C are infectious until they’re treated,” Dr. Gonzalez said. “If they don’t know that they have hepatitis C, they continue to transmit the virus to others.”

One study found that half of people living with HCV are unaware of their infection (PLoS One. 2014 Jul 2;9[7]:e101554). According to Dr. Gonzalez, forthcoming guidelines from the U.S. Preventive Services Task Force are expected to recommend a one-time screening for HCV infection in all adults aged 18-79 years, a Grade B recommendation. “That’s a big deal,” he said. (The draft recommendations are available here.)

HCV infection disproportionately affects individuals in correctional institutions. In fact, an estimated one in three inmates in the United States has chronic HCV.

“This is sort of a forgotten population with a lot of substance use and mental illness,” Dr. Gonzalez said. “Injection drug use in that setting is the most common risk factor: It’s about 60% in terms of the risk of transmission within correctional settings. HCV-associated liver disease has now surpassed HIV as a cause of death within correctional settings.”
 

Weighing treatment options

The most common oral regimens for chronic HCV include sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. They achieve cure in 93%-100% of cases.

“HCV can be cured; it can be eradicated from the body long term,” Dr. Gonzalez said. “The choice of regimen, treatment duration, and use of ribavirin depends on the presence/absence of cirrhosis, prior treatment experience, and the genotype.”

All six forms of the HCV genotype can be treated with oral medication, he added, and methadone, bupropion, and naloxone are safe to use during therapy.

Reinfection following HCV treatment occurs infrequently. Dr. Gonzalez cited a randomized, controlled trial presented as an abstract at the 2018 annual meeting of the American Association for the Study of Liver Diseases. That study’s researchers found that – among 199 patients on opioid-replacement therapy who were receiving direct-acting antiviral therapy, in whom greater than 50% were actively using drugs – the rate of reinfection at 3 years was 1.8 reinfections/100 person-years.

“That’s lower than people expect,” Dr. Gonzalez said.
 

How to boost screening

Electronic health record systems can be used as an important tool to increase HCV screening in health care settings.

In 2017, researchers published an analysis of three randomized trials carried out at three separate primary care settings to improve screening for HCV: repeated mailings, an EHR best practice alert (BPA), and patient solicitation (Hepatology 2017 Jan;65[1]:44-53). They evaluated HCV antibody testing, diagnosis, and costs for each of the interventions, compared with standard-of-care testing.

The investigators found that the BPA intervention had the lowest incremental cost per completed test – $24 with fixed start-up costs, including technical design and development of the BPA system; $3 without fixed start-up costs. The BPA intervention also had the lowest incremental cost per new case identified.

Other efforts to expand access to screening and treatment are underway.

In 2019, Louisiana health officials negotiated a one-time fee for unlimited access for 5 years to sofosbuvir/velpatasvir (Epclusa) to treat the estimated 30,000 patients on Louisiana Medicaid and in that state’s department of corrections who have HCV.

“The goal is 90% cure; the burden is on the state health department to screen, diagnose, and dispense medication,” Dr. Gonzalez said.

Also in 2019, the state of Washington used an open bidding process to negotiate access to glecaprevir/pibrentasvir (Mavyret) for the state’s Medicaid population who have HCV.

“Those states are setting the pace,” Dr. Gonzalez said. “They are showing examples of how we can start implementing a process to treat these vulnerable populations.”

Meanwhile, the World Health Organization set a goal of eliminating viral hepatitis as a major public health threat by 2030.

“That sounds ambitious, but I think it’s possible,” Dr. Gonzalez said. “It’s important to address these high-risk populations: the incarcerated, people who use drugs, and the homeless, because those are the groups that have a high prevalence of HCV – mainly through injection drug use.

“If we don’t address that population, and we only target the general population, we’re going to have a continual source of transmission,” Dr. Gonzalez warned. “In that case, we would never be able to achieve elimination.”

Dr. Gonzalez disclosed that he is a member of the speakers bureau for AbbVie and Salix.

[email protected]

LAS VEGAS – Between 2010 and 2017, the proportion of newly diagnosed cases of acute hepatitis C virus infection rose threefold, driven largely by the concomitant opioid epidemic.

Doug Brunk/MDedge News

That makes efforts to screen, diagnose, and cure high-risk populations more important than ever, Stevan A. Gonzalez, MD, said at an annual psychopharmacology update held by the Nevada Psychiatric Association.

About 70% of HCV cases are related to injection drug use,” said Dr. Gonzalez, medical director of liver transplantation at the Baylor Simmons Transplant Institute at the Baylor Scott & White All Saints Medical Center in Fort Worth, Tex. “This is affecting whites as much as blacks and Hispanics, females as much as males, and in nonurban areas as much as in urban areas.”

Data from the Centers for Disease Control and Prevention and the Substance Abuse and Mental Health Services Administration indicate that during 2004-2014, the number of acute HCV cases among those aged 18-29 years increased 400%, and the use of injection opioids rose 600%.

At the same time, the number of HCV cases among those aged 30-39 years increased 325%, and the use of injection opioids rose 83%.

“We’re starting to see a pattern overlapping between HCV exposure and opioid injection,” Dr. Gonzalez said. Other high-risk populations include homeless and incarcerated individuals.

More than 70 million people worldwide have chronic HCV infection, Dr. Gonzalez noted, with possibly as many as 5 million cases in the United States. It remains the nation’s most common blood-borne infection.

Chronic disease develops in up to 85% of people who are exposed, infection is asymptomatic, and HCV remains one of the leading indications for liver transplantation and causes of liver cancer.

From a geographic standpoint, the prevalence of HCV in young adults is eclipsing that of Baby Boomers in several states in the Appalachian region and in Northeast, which have long been trouble spots for opioid use disorder (Gastroenterol. 2018 May;154[6]:1850-1).

Surprising exposure risk

The primary risk of transmission is through contaminated blood and the exposure through needles.

“It really doesn’t matter whether it’s a needle that has a small amount of dead space where a little bit of blood can remain or needles that have a larger amount of blood,” Dr. Gonzalez said.

“I’ve had patients who come to me and say, ‘I can’t believe I have HCV. It’s impossible. I always use my own needles. They’re always brand new; I’ve never shared with anybody,’” he continued.

“This is where education and awareness is so critical, because it’s not just the needles,” Dr. Gonzalez explained. “HCV can survive on inanimate objects. For example, on a tabletop surface or a water container, HCV can remain viable up to 3 weeks. In a syringe, 2 months. For that reason, HCV can also be transmitted through crack pipes and nasal drug use, where the prevalence can be up to 35%.”

The duration of a person’s HCV infection drives the transmission.

“That’s important to think about, because people who have chronic hepatitis C are infectious until they’re treated,” Dr. Gonzalez said. “If they don’t know that they have hepatitis C, they continue to transmit the virus to others.”

One study found that half of people living with HCV are unaware of their infection (PLoS One. 2014 Jul 2;9[7]:e101554). According to Dr. Gonzalez, forthcoming guidelines from the U.S. Preventive Services Task Force are expected to recommend a one-time screening for HCV infection in all adults aged 18-79 years, a Grade B recommendation. “That’s a big deal,” he said. (The draft recommendations are available here.)

HCV infection disproportionately affects individuals in correctional institutions. In fact, an estimated one in three inmates in the United States has chronic HCV.

“This is sort of a forgotten population with a lot of substance use and mental illness,” Dr. Gonzalez said. “Injection drug use in that setting is the most common risk factor: It’s about 60% in terms of the risk of transmission within correctional settings. HCV-associated liver disease has now surpassed HIV as a cause of death within correctional settings.”
 

Weighing treatment options

The most common oral regimens for chronic HCV include sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. They achieve cure in 93%-100% of cases.

“HCV can be cured; it can be eradicated from the body long term,” Dr. Gonzalez said. “The choice of regimen, treatment duration, and use of ribavirin depends on the presence/absence of cirrhosis, prior treatment experience, and the genotype.”

All six forms of the HCV genotype can be treated with oral medication, he added, and methadone, bupropion, and naloxone are safe to use during therapy.

Reinfection following HCV treatment occurs infrequently. Dr. Gonzalez cited a randomized, controlled trial presented as an abstract at the 2018 annual meeting of the American Association for the Study of Liver Diseases. That study’s researchers found that – among 199 patients on opioid-replacement therapy who were receiving direct-acting antiviral therapy, in whom greater than 50% were actively using drugs – the rate of reinfection at 3 years was 1.8 reinfections/100 person-years.

“That’s lower than people expect,” Dr. Gonzalez said.
 

How to boost screening

Electronic health record systems can be used as an important tool to increase HCV screening in health care settings.

In 2017, researchers published an analysis of three randomized trials carried out at three separate primary care settings to improve screening for HCV: repeated mailings, an EHR best practice alert (BPA), and patient solicitation (Hepatology 2017 Jan;65[1]:44-53). They evaluated HCV antibody testing, diagnosis, and costs for each of the interventions, compared with standard-of-care testing.

The investigators found that the BPA intervention had the lowest incremental cost per completed test – $24 with fixed start-up costs, including technical design and development of the BPA system; $3 without fixed start-up costs. The BPA intervention also had the lowest incremental cost per new case identified.

Other efforts to expand access to screening and treatment are underway.

In 2019, Louisiana health officials negotiated a one-time fee for unlimited access for 5 years to sofosbuvir/velpatasvir (Epclusa) to treat the estimated 30,000 patients on Louisiana Medicaid and in that state’s department of corrections who have HCV.

“The goal is 90% cure; the burden is on the state health department to screen, diagnose, and dispense medication,” Dr. Gonzalez said.

Also in 2019, the state of Washington used an open bidding process to negotiate access to glecaprevir/pibrentasvir (Mavyret) for the state’s Medicaid population who have HCV.

“Those states are setting the pace,” Dr. Gonzalez said. “They are showing examples of how we can start implementing a process to treat these vulnerable populations.”

Meanwhile, the World Health Organization set a goal of eliminating viral hepatitis as a major public health threat by 2030.

“That sounds ambitious, but I think it’s possible,” Dr. Gonzalez said. “It’s important to address these high-risk populations: the incarcerated, people who use drugs, and the homeless, because those are the groups that have a high prevalence of HCV – mainly through injection drug use.

“If we don’t address that population, and we only target the general population, we’re going to have a continual source of transmission,” Dr. Gonzalez warned. “In that case, we would never be able to achieve elimination.”

Dr. Gonzalez disclosed that he is a member of the speakers bureau for AbbVie and Salix.

[email protected]

In late January, the Crohn’s & Colitis Foundation teamed with AGA to present the Crohn’s & Colitis Congress^® in Austin, Tex. Each year, this is the premier gathering for IBD experts and the rest of us to catch up on the substantial progress we are making in treating patients with IBD. This month, we highlight a number of articles from the Congress, including results showing how a focused IBD quality initiative reduced emergency department visits, an article about the effects of IBD on fertility, and the link between stress and ulcerative colitis flares. All of these articles are worth reading, since they can help our care of patients. On agau.gastro.org, you can access slides from the Congress.

Several more articles deserve mention. Three articles from the AGA journals highlight new information about colorectal cancer prevention and the U.S. Multi-Society Task Force on Colorectal Cancer has updated colonoscopy follow-up guidance. In our practice management section, we provide a step-by-step guide to changes in evaluation and management (E/M) coding – these changes are the most impactful since the Medicare E/M documentation specifications first appeared.

We have 2 months left before Digestive Disease Week^® (DDW). Each year, DDW marks the end of our AGA Institute President’s term and the beginning of another’s epoch. Hashem B. El-Serag will pass the gavel to Bishr Omary – both great friends and great gastroenterologists. I am happy to see that Gail Hecht follows me as this year’s AGA Julius Friedenwald Medal recipient (AGA’s highest honor). She, too, is a great friend and role model for me and many others. DDW returns to Chicago in early May, and once again will be the world’s best gathering of physicians and scientists dedicated to digestive diseases.
 

John I. Allen, MD, MBA, AGAF
Editor in Chief

In late January, the Crohn’s & Colitis Foundation teamed with AGA to present the Crohn’s & Colitis Congress^® in Austin, Tex. Each year, this is the premier gathering for IBD experts and the rest of us to catch up on the substantial progress we are making in treating patients with IBD. This month, we highlight a number of articles from the Congress, including results showing how a focused IBD quality initiative reduced emergency department visits, an article about the effects of IBD on fertility, and the link between stress and ulcerative colitis flares. All of these articles are worth reading, since they can help our care of patients. On agau.gastro.org, you can access slides from the Congress.

Several more articles deserve mention. Three articles from the AGA journals highlight new information about colorectal cancer prevention and the U.S. Multi-Society Task Force on Colorectal Cancer has updated colonoscopy follow-up guidance. In our practice management section, we provide a step-by-step guide to changes in evaluation and management (E/M) coding – these changes are the most impactful since the Medicare E/M documentation specifications first appeared.

We have 2 months left before Digestive Disease Week^® (DDW). Each year, DDW marks the end of our AGA Institute President’s term and the beginning of another’s epoch. Hashem B. El-Serag will pass the gavel to Bishr Omary – both great friends and great gastroenterologists. I am happy to see that Gail Hecht follows me as this year’s AGA Julius Friedenwald Medal recipient (AGA’s highest honor). She, too, is a great friend and role model for me and many others. DDW returns to Chicago in early May, and once again will be the world’s best gathering of physicians and scientists dedicated to digestive diseases.
 

John I. Allen, MD, MBA, AGAF
Editor in Chief

In late January, the Crohn’s & Colitis Foundation teamed with AGA to present the Crohn’s & Colitis Congress^® in Austin, Tex. Each year, this is the premier gathering for IBD experts and the rest of us to catch up on the substantial progress we are making in treating patients with IBD. This month, we highlight a number of articles from the Congress, including results showing how a focused IBD quality initiative reduced emergency department visits, an article about the effects of IBD on fertility, and the link between stress and ulcerative colitis flares. All of these articles are worth reading, since they can help our care of patients. On agau.gastro.org, you can access slides from the Congress.

Several more articles deserve mention. Three articles from the AGA journals highlight new information about colorectal cancer prevention and the U.S. Multi-Society Task Force on Colorectal Cancer has updated colonoscopy follow-up guidance. In our practice management section, we provide a step-by-step guide to changes in evaluation and management (E/M) coding – these changes are the most impactful since the Medicare E/M documentation specifications first appeared.

We have 2 months left before Digestive Disease Week^® (DDW). Each year, DDW marks the end of our AGA Institute President’s term and the beginning of another’s epoch. Hashem B. El-Serag will pass the gavel to Bishr Omary – both great friends and great gastroenterologists. I am happy to see that Gail Hecht follows me as this year’s AGA Julius Friedenwald Medal recipient (AGA’s highest honor). She, too, is a great friend and role model for me and many others. DDW returns to Chicago in early May, and once again will be the world’s best gathering of physicians and scientists dedicated to digestive diseases.
 

John I. Allen, MD, MBA, AGAF
Editor in Chief

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.