The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) approved new recommendations for hepatitis A vaccinations, including a focus on catch-up vaccines for adolescents and those over age 40 years.

While hepatitis A cases have dropped significantly since the vaccine’s debut – with the number of reported cases in 2015 dropping to 1,390, compared with 9,606 in 1971 – previous recommendations regarding catch-up vaccinations suggested patients should consider treatment, as opposed to catch-up vaccination.

jarun011/Thinkstock

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) approved new recommendations for hepatitis A vaccinations, including a focus on catch-up vaccines for adolescents and those over age 40 years.

While hepatitis A cases have dropped significantly since the vaccine’s debut – with the number of reported cases in 2015 dropping to 1,390, compared with 9,606 in 1971 – previous recommendations regarding catch-up vaccinations suggested patients should consider treatment, as opposed to catch-up vaccination.

jarun011/Thinkstock

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) approved new recommendations for hepatitis A vaccinations, including a focus on catch-up vaccines for adolescents and those over age 40 years.

While hepatitis A cases have dropped significantly since the vaccine’s debut – with the number of reported cases in 2015 dropping to 1,390, compared with 9,606 in 1971 – previous recommendations regarding catch-up vaccinations suggested patients should consider treatment, as opposed to catch-up vaccination.

jarun011/Thinkstock

ezimmerman@frontlinemedcom.com

On Twitter @eaztweets

CHICAGO – Overall survival was comparable at 5 years of follow up for three regimens in treatment-naive patients with indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL), based on long-term results from the BRIGHT study.

While progression-free survival, event-free survival, and duration of response were significantly better with bendamustine plus rituximab (BR), overall survival at 5 years did not significantly differ in patients given this regimen and compared to patients given rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP), Ian Flinn, MD, of Tennessee Oncology, Nashville, reported at the annual meeting of the American Society of Clinical Oncology.

Mary Jo M. Dales/Frontline Medical News

Mary Jo M. Dales/Frontline Medical News

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Overall survival was comparable at 5 years of follow up for three regimens in treatment-naive patients with indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL), based on long-term results from the BRIGHT study.

While progression-free survival, event-free survival, and duration of response were significantly better with bendamustine plus rituximab (BR), overall survival at 5 years did not significantly differ in patients given this regimen and compared to patients given rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP), Ian Flinn, MD, of Tennessee Oncology, Nashville, reported at the annual meeting of the American Society of Clinical Oncology.

Mary Jo M. Dales/Frontline Medical News

Mary Jo M. Dales/Frontline Medical News

mdales@frontlinemedcom.com

On Twitter @maryjodales

CHICAGO – Overall survival was comparable at 5 years of follow up for three regimens in treatment-naive patients with indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL), based on long-term results from the BRIGHT study.

While progression-free survival, event-free survival, and duration of response were significantly better with bendamustine plus rituximab (BR), overall survival at 5 years did not significantly differ in patients given this regimen and compared to patients given rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP), Ian Flinn, MD, of Tennessee Oncology, Nashville, reported at the annual meeting of the American Society of Clinical Oncology.

Mary Jo M. Dales/Frontline Medical News

Mary Jo M. Dales/Frontline Medical News

mdales@frontlinemedcom.com

On Twitter @maryjodales

If you are a hospitalist and leader in your health care organization, the ongoing controversies surrounding the Affordable Care Act repeal and replace campaign are unsettling. No matter your politics, Washington’s political drama and gamesmanship pose a genuine threat to the solvency of your hospital’s budget, services, workforce, and patients.

Health care has devolved into a political football, tossed from skirmish to skirmish. Political leaders warn of the implosion of the health care system as a political tactic, not an outcome that could cost and ruin lives. Both Democrats and Republicans hope that if or when that happens, it does so in ways that allow them to blame the other side. For them, this is a game of partisan advantage that wagers the well-being of your health care system.

Leonard J. Marcus, Ph.D. is coauthor of Renegotiating Health Care: Resolving Conflict to Build Collaboration, Second Edition (San Francisco: Jossey-Bass Publishers, 2011) and is director of the program for health care negotiation and conflict resolution, Harvard T.H. Chan School of Public Health. Dr. Marcus teaches regularly in the SHM Leadership Academy. He can be reached at ljmarcus@hsph.harvard.edu

If you are a hospitalist and leader in your health care organization, the ongoing controversies surrounding the Affordable Care Act repeal and replace campaign are unsettling. No matter your politics, Washington’s political drama and gamesmanship pose a genuine threat to the solvency of your hospital’s budget, services, workforce, and patients.

Health care has devolved into a political football, tossed from skirmish to skirmish. Political leaders warn of the implosion of the health care system as a political tactic, not an outcome that could cost and ruin lives. Both Democrats and Republicans hope that if or when that happens, it does so in ways that allow them to blame the other side. For them, this is a game of partisan advantage that wagers the well-being of your health care system.

Leonard J. Marcus, Ph.D. is coauthor of Renegotiating Health Care: Resolving Conflict to Build Collaboration, Second Edition (San Francisco: Jossey-Bass Publishers, 2011) and is director of the program for health care negotiation and conflict resolution, Harvard T.H. Chan School of Public Health. Dr. Marcus teaches regularly in the SHM Leadership Academy. He can be reached at ljmarcus@hsph.harvard.edu

If you are a hospitalist and leader in your health care organization, the ongoing controversies surrounding the Affordable Care Act repeal and replace campaign are unsettling. No matter your politics, Washington’s political drama and gamesmanship pose a genuine threat to the solvency of your hospital’s budget, services, workforce, and patients.

Health care has devolved into a political football, tossed from skirmish to skirmish. Political leaders warn of the implosion of the health care system as a political tactic, not an outcome that could cost and ruin lives. Both Democrats and Republicans hope that if or when that happens, it does so in ways that allow them to blame the other side. For them, this is a game of partisan advantage that wagers the well-being of your health care system.

Leonard J. Marcus, Ph.D. is coauthor of Renegotiating Health Care: Resolving Conflict to Build Collaboration, Second Edition (San Francisco: Jossey-Bass Publishers, 2011) and is director of the program for health care negotiation and conflict resolution, Harvard T.H. Chan School of Public Health. Dr. Marcus teaches regularly in the SHM Leadership Academy. He can be reached at ljmarcus@hsph.harvard.edu

First named by Steven Bratman in 1997, orthorexia nervosa (ON) from the Greek ortho, meaning correct, and orexi, meaning appetite, is classified as an unspecified feeding and eating disorder in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5).^1,2

Hypothetical Case

Mr. P is a 30-year-old male who presented to the mental health clinic with his wife. The patient recounted that he had wanted to “be healthy” since childhood and has focused on exercise and proper diet, but anxiety about diet and food intake have steadily increased. Two years ago, he adopted a vegetarian diet by progressively eliminating several foods and food groups from his diet. He now feels “proud” to eat certain organically grown fruits, vegetables, nuts, beans, and drink only fruit or vegetable juice.

His wife stated that he spent between 3 and 5 hours daily preparing food or talking to friends and family about “correct foods to eat.” He also believed that errors in dietary habits caused physical or mental illnesses. He reported significant guilt and shame whenever he “slips up” on his dietary regimen and eats anything containing seafood, beef, or pork products, which he corrects by a day of fasting. His wife was frustrated because he refused to go to restaurants and started declining offers from friends to eat dinner at their homes unless he could bring his prepared food. He describes feeling “annoyed” when he sees other people eating fast food or meat.

Mr. P reported no significant medical or surgical history. His family history was significant for anxiety in his mother. He used to drink alcohol socially but ceased a few years ago due to its carbohydrate content. He never smoked or used illicit drugs.

A mental status exam revealed a thin male who appeared his stated age. He was cooperative, casually dressed, and made fair eye contact. He spoke clearly with an anxious tone and appropriate rate and volume. His affect was congruent with stated anxious mood. He was alert, awake, and oriented to person, place, and time. He reported no paranoia, auditory or visual hallucinations, and suicidal or homicidal ideation.

A physical exam revealed a thin male in no distress who measured 5 feet 10 inches tall and weighed 145 pounds, which yielded a body mass index of 20.8. His vitals included temperature of 98° F, blood pressure 115/76, pulse 74, and oxygen saturation 98% on room air. The remaining physical examination revealed no abnormalities. A complete blood count, thyroid function, urinalysis, and urine drug screens were within normal limits. Comprehensive metabolic profile revealed decreased sodium of 130 meq/L. Electrocardiogram revealed bradycardia.

An ON diagnosis is made primarily through a clinical interview. Collateral information from individuals familiar with the patient can be helpful. Experts have proposed and recently revised criteria for ON (Table). Although the ORTO-15 assessment tool may assist with diagnosis, the tool does not substitute for the clinical interview.

Discussion

There is no reliable measure of prevalence of ON, though Varga and colleagues initially estimated ON to occur in 6.9% of the general population, and ON may occur more frequently in health care professionals and performance artists.³ However, these may be overestimates, as the assessment tool used in the study does not adequately separate people with healthy eating habits from those with ON.^4,5

Most prevalence studies were conducted in Europe and Turkey, and prevalence of ON may differ in the U.S. population. A recent assessment determined a prevalence of about 1%, similar to that of other eating disorders.⁵ No study has reported a correlation between ON and gender, but a survey of 448 college students in the U.S. (mean age 22 years) reported highest ON tendencies in Hispanic/Latino and overweight/obese students.⁶

Relationship to Other Illnesses

There is significant debate whether ON is a single syndrome, a variance of other syndromes, or a behavioral and culturally influenced attitude.^7,8 Although ON may lead to or be comorbid with anorexia nervosa (AN) or obsessive-compulsive disorder (OCD), subtle differences exist between ON and these conditions.

To meet DSM-5 diagnostic criteria for AN, patients must weigh below minimally normal weight for their height and age, have an intense fear of gaining weight or becoming fat, and have a disturbed experience of their weight or body shape or cannot recognize the severity of the low weight.² In contrast, an individual with ON may possess normal or low-normal weight. Patients with AN focus on food quantity, while patients with ON tend to focus on food quality. As summarized by Bratman, “People are ashamed of their anorexia, but they actively evangelize their orthorexia. People with anorexia skip meals; people with orthorexia do not (unless they are fasting). Those with anorexia focus only on avoiding foods, while those with orthorexia both avoid foods they think are bad and embrace foods they think are super-healthy.”⁹

Similarities between ON and OCD include anxiety, a need to exert control, and perfectionism. However, patients with OCD tend to report distress from compulsive behavior and a desire to change, thus exhibiting insight into their illness.^8,10 Similarities between obsessive-compulsive personality disorder (OCPD) and ON include perfectionism, rigid thinking, excessive devotion, hypermorality, and a preoccupation with details and perceived rules.¹¹

While no studies have yet described ON as a feature of somatoform disorders, some experts have hypothesized that preoccupation with illness in a patient with somatization disorder may engender a preoccupation with food and diet as a way to combat either real or perceived illness.¹¹ Finally, there is a report of ON associated with the prodromal phase of schizophrenia, and the development of ON may increase risk for future psychotic disorders.^11,12

Pathophysiology

The exact cause of ON is unknown, though it is likely multifactorial. Individuals with ON have neurocognitive deficits similar to those seen in patients with AN and OCD, including impairments in set-shifting (flexible problem solving), external attention, and working memory.^11,13 Given these cognitive deficits as well as similar symptomatology, there may be analogous brain dysfunction in patients with ON and AN or OCD. Neuroimaging studies of patients with AN have revealed dysregulation of dopamine transmission in the reward circuitry of the ventral striatum and the food regulatory mechanism in the hypothalamus.¹⁴

Dysmorphology of and dysfunction in neural circuitry, particularly the cortico-striato-thalamo-cortical pathway, have been implicated in OCD.¹⁵ Neuroimaging studies have revealed increased volume and activation of the orbitofrontal cortex, which may be associated with obsessions and difficulty with extinction recall.^14,15 In contrast, decreased volume and activity of the thalamus may impair its ability to inhibit the orbitofrontal cortex.^15,16 Decreased volume and activity of the cingulate gyrus may be associated with difficulty in error monitoring and fear conditioning, while overactivation of the parietal lobe and cerebellum may be associated with compulsive behaviors.^15,16

Risk Factors

Factors that contribute to the development of AN and possibly ON include development of food preferences, inherited differences in taste perception, food neophobia or pickiness, being premorbidly overweight or obese, parental feeding practices, and a history of parental eating disorders.¹⁴ One survey associated orthorexic tendencies with perfectionism, appearance orientation, overweight preoccupation, self-classified weight, and fearful and dismissing attachment styles.¹⁷ Significant predictors of ON included overweight preoccupation, appearance orientation, and a history of an eating disorder.¹⁷

Treatment

In contrast to patients with AN, patients with ON may be easily amenable to treatment, given their pursuit of and emphasis on wellness.¹⁸ Experts recommend a multidisciplinary team approach that includes physicians, psychotherapists, and dieticians.¹¹ Treatment may be undertaken in an outpatient setting, but hospitalization for refeeding is recommended in cases with significant weight loss or malnourishment.¹¹ Physical examination and laboratory studies are warranted, as excessive dietary restrictions can lead to weight loss and medical complications similar to those seen in AN, including osteopenia, anemia, hyponatremia, pancytopenia, bradycardia, and even pneumothorax and pneumomediastinum.^19-21

There are no reported studies exploring the efficacy of psychotherapy or psychotropic medications for patients with ON. However, several treatments have been proposed given the symptom overlap with AN. Serotonin reuptake inhibitors may be beneficial for anxiety and obsessive-compulsive traits.¹⁸ However, patients with ON may refuse medications as unnatural substances.¹⁸

Cognitive behavioral therapy may be beneficial to address perfectionism and cognitive distortions, and exposure and response prevention may reduce obsessive-compulsive behaviors.¹¹ Relaxation therapy may reduce mealtime anxiety. Psychoeducation may correct inaccurate beliefs about food groups, purity, and preparation, but it may induce emotional stress for the patient with ON.¹¹

Conclusion

Orthorexia nervosa is perhaps best summarized as an obsession with healthy eating with associated restrictive behaviors. However, the attempt to attain optimum health through attention to diet may lead to malnourishment, loss of relationships, and poor quality of life.¹¹ It is a little-understood disorder with uncertain etiology, imprecise assessment tools, and no formal diagnostic criteria or classification. Orthorexic characteristics vary from normal to pathologic in degree, and making a diagnosis remains a clinical judgment.²² Further research is needed to develop valid diagnostic tools and determining whether ON should be classified as a unique illness or a variation of other eating or anxiety disorders. Further research also may identify the etiology of ON, thus enabling targeted multidisciplinary treatment.

First named by Steven Bratman in 1997, orthorexia nervosa (ON) from the Greek ortho, meaning correct, and orexi, meaning appetite, is classified as an unspecified feeding and eating disorder in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5).^1,2

Hypothetical Case

Mr. P is a 30-year-old male who presented to the mental health clinic with his wife. The patient recounted that he had wanted to “be healthy” since childhood and has focused on exercise and proper diet, but anxiety about diet and food intake have steadily increased. Two years ago, he adopted a vegetarian diet by progressively eliminating several foods and food groups from his diet. He now feels “proud” to eat certain organically grown fruits, vegetables, nuts, beans, and drink only fruit or vegetable juice.

His wife stated that he spent between 3 and 5 hours daily preparing food or talking to friends and family about “correct foods to eat.” He also believed that errors in dietary habits caused physical or mental illnesses. He reported significant guilt and shame whenever he “slips up” on his dietary regimen and eats anything containing seafood, beef, or pork products, which he corrects by a day of fasting. His wife was frustrated because he refused to go to restaurants and started declining offers from friends to eat dinner at their homes unless he could bring his prepared food. He describes feeling “annoyed” when he sees other people eating fast food or meat.

Mr. P reported no significant medical or surgical history. His family history was significant for anxiety in his mother. He used to drink alcohol socially but ceased a few years ago due to its carbohydrate content. He never smoked or used illicit drugs.

A mental status exam revealed a thin male who appeared his stated age. He was cooperative, casually dressed, and made fair eye contact. He spoke clearly with an anxious tone and appropriate rate and volume. His affect was congruent with stated anxious mood. He was alert, awake, and oriented to person, place, and time. He reported no paranoia, auditory or visual hallucinations, and suicidal or homicidal ideation.

A physical exam revealed a thin male in no distress who measured 5 feet 10 inches tall and weighed 145 pounds, which yielded a body mass index of 20.8. His vitals included temperature of 98° F, blood pressure 115/76, pulse 74, and oxygen saturation 98% on room air. The remaining physical examination revealed no abnormalities. A complete blood count, thyroid function, urinalysis, and urine drug screens were within normal limits. Comprehensive metabolic profile revealed decreased sodium of 130 meq/L. Electrocardiogram revealed bradycardia.

An ON diagnosis is made primarily through a clinical interview. Collateral information from individuals familiar with the patient can be helpful. Experts have proposed and recently revised criteria for ON (Table). Although the ORTO-15 assessment tool may assist with diagnosis, the tool does not substitute for the clinical interview.

Discussion

There is no reliable measure of prevalence of ON, though Varga and colleagues initially estimated ON to occur in 6.9% of the general population, and ON may occur more frequently in health care professionals and performance artists.³ However, these may be overestimates, as the assessment tool used in the study does not adequately separate people with healthy eating habits from those with ON.^4,5

Most prevalence studies were conducted in Europe and Turkey, and prevalence of ON may differ in the U.S. population. A recent assessment determined a prevalence of about 1%, similar to that of other eating disorders.⁵ No study has reported a correlation between ON and gender, but a survey of 448 college students in the U.S. (mean age 22 years) reported highest ON tendencies in Hispanic/Latino and overweight/obese students.⁶

Relationship to Other Illnesses

There is significant debate whether ON is a single syndrome, a variance of other syndromes, or a behavioral and culturally influenced attitude.^7,8 Although ON may lead to or be comorbid with anorexia nervosa (AN) or obsessive-compulsive disorder (OCD), subtle differences exist between ON and these conditions.

To meet DSM-5 diagnostic criteria for AN, patients must weigh below minimally normal weight for their height and age, have an intense fear of gaining weight or becoming fat, and have a disturbed experience of their weight or body shape or cannot recognize the severity of the low weight.² In contrast, an individual with ON may possess normal or low-normal weight. Patients with AN focus on food quantity, while patients with ON tend to focus on food quality. As summarized by Bratman, “People are ashamed of their anorexia, but they actively evangelize their orthorexia. People with anorexia skip meals; people with orthorexia do not (unless they are fasting). Those with anorexia focus only on avoiding foods, while those with orthorexia both avoid foods they think are bad and embrace foods they think are super-healthy.”⁹

Similarities between ON and OCD include anxiety, a need to exert control, and perfectionism. However, patients with OCD tend to report distress from compulsive behavior and a desire to change, thus exhibiting insight into their illness.^8,10 Similarities between obsessive-compulsive personality disorder (OCPD) and ON include perfectionism, rigid thinking, excessive devotion, hypermorality, and a preoccupation with details and perceived rules.¹¹

While no studies have yet described ON as a feature of somatoform disorders, some experts have hypothesized that preoccupation with illness in a patient with somatization disorder may engender a preoccupation with food and diet as a way to combat either real or perceived illness.¹¹ Finally, there is a report of ON associated with the prodromal phase of schizophrenia, and the development of ON may increase risk for future psychotic disorders.^11,12

Pathophysiology

The exact cause of ON is unknown, though it is likely multifactorial. Individuals with ON have neurocognitive deficits similar to those seen in patients with AN and OCD, including impairments in set-shifting (flexible problem solving), external attention, and working memory.^11,13 Given these cognitive deficits as well as similar symptomatology, there may be analogous brain dysfunction in patients with ON and AN or OCD. Neuroimaging studies of patients with AN have revealed dysregulation of dopamine transmission in the reward circuitry of the ventral striatum and the food regulatory mechanism in the hypothalamus.¹⁴

Dysmorphology of and dysfunction in neural circuitry, particularly the cortico-striato-thalamo-cortical pathway, have been implicated in OCD.¹⁵ Neuroimaging studies have revealed increased volume and activation of the orbitofrontal cortex, which may be associated with obsessions and difficulty with extinction recall.^14,15 In contrast, decreased volume and activity of the thalamus may impair its ability to inhibit the orbitofrontal cortex.^15,16 Decreased volume and activity of the cingulate gyrus may be associated with difficulty in error monitoring and fear conditioning, while overactivation of the parietal lobe and cerebellum may be associated with compulsive behaviors.^15,16

Risk Factors

Factors that contribute to the development of AN and possibly ON include development of food preferences, inherited differences in taste perception, food neophobia or pickiness, being premorbidly overweight or obese, parental feeding practices, and a history of parental eating disorders.¹⁴ One survey associated orthorexic tendencies with perfectionism, appearance orientation, overweight preoccupation, self-classified weight, and fearful and dismissing attachment styles.¹⁷ Significant predictors of ON included overweight preoccupation, appearance orientation, and a history of an eating disorder.¹⁷

Treatment

In contrast to patients with AN, patients with ON may be easily amenable to treatment, given their pursuit of and emphasis on wellness.¹⁸ Experts recommend a multidisciplinary team approach that includes physicians, psychotherapists, and dieticians.¹¹ Treatment may be undertaken in an outpatient setting, but hospitalization for refeeding is recommended in cases with significant weight loss or malnourishment.¹¹ Physical examination and laboratory studies are warranted, as excessive dietary restrictions can lead to weight loss and medical complications similar to those seen in AN, including osteopenia, anemia, hyponatremia, pancytopenia, bradycardia, and even pneumothorax and pneumomediastinum.^19-21

There are no reported studies exploring the efficacy of psychotherapy or psychotropic medications for patients with ON. However, several treatments have been proposed given the symptom overlap with AN. Serotonin reuptake inhibitors may be beneficial for anxiety and obsessive-compulsive traits.¹⁸ However, patients with ON may refuse medications as unnatural substances.¹⁸

Cognitive behavioral therapy may be beneficial to address perfectionism and cognitive distortions, and exposure and response prevention may reduce obsessive-compulsive behaviors.¹¹ Relaxation therapy may reduce mealtime anxiety. Psychoeducation may correct inaccurate beliefs about food groups, purity, and preparation, but it may induce emotional stress for the patient with ON.¹¹

Conclusion

Orthorexia nervosa is perhaps best summarized as an obsession with healthy eating with associated restrictive behaviors. However, the attempt to attain optimum health through attention to diet may lead to malnourishment, loss of relationships, and poor quality of life.¹¹ It is a little-understood disorder with uncertain etiology, imprecise assessment tools, and no formal diagnostic criteria or classification. Orthorexic characteristics vary from normal to pathologic in degree, and making a diagnosis remains a clinical judgment.²² Further research is needed to develop valid diagnostic tools and determining whether ON should be classified as a unique illness or a variation of other eating or anxiety disorders. Further research also may identify the etiology of ON, thus enabling targeted multidisciplinary treatment.

First named by Steven Bratman in 1997, orthorexia nervosa (ON) from the Greek ortho, meaning correct, and orexi, meaning appetite, is classified as an unspecified feeding and eating disorder in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5).^1,2

Hypothetical Case

Mr. P is a 30-year-old male who presented to the mental health clinic with his wife. The patient recounted that he had wanted to “be healthy” since childhood and has focused on exercise and proper diet, but anxiety about diet and food intake have steadily increased. Two years ago, he adopted a vegetarian diet by progressively eliminating several foods and food groups from his diet. He now feels “proud” to eat certain organically grown fruits, vegetables, nuts, beans, and drink only fruit or vegetable juice.

His wife stated that he spent between 3 and 5 hours daily preparing food or talking to friends and family about “correct foods to eat.” He also believed that errors in dietary habits caused physical or mental illnesses. He reported significant guilt and shame whenever he “slips up” on his dietary regimen and eats anything containing seafood, beef, or pork products, which he corrects by a day of fasting. His wife was frustrated because he refused to go to restaurants and started declining offers from friends to eat dinner at their homes unless he could bring his prepared food. He describes feeling “annoyed” when he sees other people eating fast food or meat.

Mr. P reported no significant medical or surgical history. His family history was significant for anxiety in his mother. He used to drink alcohol socially but ceased a few years ago due to its carbohydrate content. He never smoked or used illicit drugs.

A mental status exam revealed a thin male who appeared his stated age. He was cooperative, casually dressed, and made fair eye contact. He spoke clearly with an anxious tone and appropriate rate and volume. His affect was congruent with stated anxious mood. He was alert, awake, and oriented to person, place, and time. He reported no paranoia, auditory or visual hallucinations, and suicidal or homicidal ideation.

A physical exam revealed a thin male in no distress who measured 5 feet 10 inches tall and weighed 145 pounds, which yielded a body mass index of 20.8. His vitals included temperature of 98° F, blood pressure 115/76, pulse 74, and oxygen saturation 98% on room air. The remaining physical examination revealed no abnormalities. A complete blood count, thyroid function, urinalysis, and urine drug screens were within normal limits. Comprehensive metabolic profile revealed decreased sodium of 130 meq/L. Electrocardiogram revealed bradycardia.

An ON diagnosis is made primarily through a clinical interview. Collateral information from individuals familiar with the patient can be helpful. Experts have proposed and recently revised criteria for ON (Table). Although the ORTO-15 assessment tool may assist with diagnosis, the tool does not substitute for the clinical interview.

Discussion

There is no reliable measure of prevalence of ON, though Varga and colleagues initially estimated ON to occur in 6.9% of the general population, and ON may occur more frequently in health care professionals and performance artists.³ However, these may be overestimates, as the assessment tool used in the study does not adequately separate people with healthy eating habits from those with ON.^4,5

Most prevalence studies were conducted in Europe and Turkey, and prevalence of ON may differ in the U.S. population. A recent assessment determined a prevalence of about 1%, similar to that of other eating disorders.⁵ No study has reported a correlation between ON and gender, but a survey of 448 college students in the U.S. (mean age 22 years) reported highest ON tendencies in Hispanic/Latino and overweight/obese students.⁶

Relationship to Other Illnesses

There is significant debate whether ON is a single syndrome, a variance of other syndromes, or a behavioral and culturally influenced attitude.^7,8 Although ON may lead to or be comorbid with anorexia nervosa (AN) or obsessive-compulsive disorder (OCD), subtle differences exist between ON and these conditions.

To meet DSM-5 diagnostic criteria for AN, patients must weigh below minimally normal weight for their height and age, have an intense fear of gaining weight or becoming fat, and have a disturbed experience of their weight or body shape or cannot recognize the severity of the low weight.² In contrast, an individual with ON may possess normal or low-normal weight. Patients with AN focus on food quantity, while patients with ON tend to focus on food quality. As summarized by Bratman, “People are ashamed of their anorexia, but they actively evangelize their orthorexia. People with anorexia skip meals; people with orthorexia do not (unless they are fasting). Those with anorexia focus only on avoiding foods, while those with orthorexia both avoid foods they think are bad and embrace foods they think are super-healthy.”⁹

Similarities between ON and OCD include anxiety, a need to exert control, and perfectionism. However, patients with OCD tend to report distress from compulsive behavior and a desire to change, thus exhibiting insight into their illness.^8,10 Similarities between obsessive-compulsive personality disorder (OCPD) and ON include perfectionism, rigid thinking, excessive devotion, hypermorality, and a preoccupation with details and perceived rules.¹¹

While no studies have yet described ON as a feature of somatoform disorders, some experts have hypothesized that preoccupation with illness in a patient with somatization disorder may engender a preoccupation with food and diet as a way to combat either real or perceived illness.¹¹ Finally, there is a report of ON associated with the prodromal phase of schizophrenia, and the development of ON may increase risk for future psychotic disorders.^11,12

Pathophysiology

The exact cause of ON is unknown, though it is likely multifactorial. Individuals with ON have neurocognitive deficits similar to those seen in patients with AN and OCD, including impairments in set-shifting (flexible problem solving), external attention, and working memory.^11,13 Given these cognitive deficits as well as similar symptomatology, there may be analogous brain dysfunction in patients with ON and AN or OCD. Neuroimaging studies of patients with AN have revealed dysregulation of dopamine transmission in the reward circuitry of the ventral striatum and the food regulatory mechanism in the hypothalamus.¹⁴

Dysmorphology of and dysfunction in neural circuitry, particularly the cortico-striato-thalamo-cortical pathway, have been implicated in OCD.¹⁵ Neuroimaging studies have revealed increased volume and activation of the orbitofrontal cortex, which may be associated with obsessions and difficulty with extinction recall.^14,15 In contrast, decreased volume and activity of the thalamus may impair its ability to inhibit the orbitofrontal cortex.^15,16 Decreased volume and activity of the cingulate gyrus may be associated with difficulty in error monitoring and fear conditioning, while overactivation of the parietal lobe and cerebellum may be associated with compulsive behaviors.^15,16

Risk Factors

Factors that contribute to the development of AN and possibly ON include development of food preferences, inherited differences in taste perception, food neophobia or pickiness, being premorbidly overweight or obese, parental feeding practices, and a history of parental eating disorders.¹⁴ One survey associated orthorexic tendencies with perfectionism, appearance orientation, overweight preoccupation, self-classified weight, and fearful and dismissing attachment styles.¹⁷ Significant predictors of ON included overweight preoccupation, appearance orientation, and a history of an eating disorder.¹⁷

Treatment

In contrast to patients with AN, patients with ON may be easily amenable to treatment, given their pursuit of and emphasis on wellness.¹⁸ Experts recommend a multidisciplinary team approach that includes physicians, psychotherapists, and dieticians.¹¹ Treatment may be undertaken in an outpatient setting, but hospitalization for refeeding is recommended in cases with significant weight loss or malnourishment.¹¹ Physical examination and laboratory studies are warranted, as excessive dietary restrictions can lead to weight loss and medical complications similar to those seen in AN, including osteopenia, anemia, hyponatremia, pancytopenia, bradycardia, and even pneumothorax and pneumomediastinum.^19-21

There are no reported studies exploring the efficacy of psychotherapy or psychotropic medications for patients with ON. However, several treatments have been proposed given the symptom overlap with AN. Serotonin reuptake inhibitors may be beneficial for anxiety and obsessive-compulsive traits.¹⁸ However, patients with ON may refuse medications as unnatural substances.¹⁸

Cognitive behavioral therapy may be beneficial to address perfectionism and cognitive distortions, and exposure and response prevention may reduce obsessive-compulsive behaviors.¹¹ Relaxation therapy may reduce mealtime anxiety. Psychoeducation may correct inaccurate beliefs about food groups, purity, and preparation, but it may induce emotional stress for the patient with ON.¹¹

Conclusion

Orthorexia nervosa is perhaps best summarized as an obsession with healthy eating with associated restrictive behaviors. However, the attempt to attain optimum health through attention to diet may lead to malnourishment, loss of relationships, and poor quality of life.¹¹ It is a little-understood disorder with uncertain etiology, imprecise assessment tools, and no formal diagnostic criteria or classification. Orthorexic characteristics vary from normal to pathologic in degree, and making a diagnosis remains a clinical judgment.²² Further research is needed to develop valid diagnostic tools and determining whether ON should be classified as a unique illness or a variation of other eating or anxiety disorders. Further research also may identify the etiology of ON, thus enabling targeted multidisciplinary treatment.

14th International Conference on Malignant Lymphoma (ICML)

LUGANO, SWITZERLAND—Interim results of a phase 2 trial suggest tazemetostat can be effective in patients with heavily pretreated, relapsed or refractory non-Hodgkin lymphoma.

The EZH2 inhibitor produced the highest overall response rate in patients with EZH2-mutated follicular lymphoma (FL), followed by EZH2-mutated diffuse large B-cell lymphoma (DLBCL).

However, the drug also produced complete responses in FL and DLBCL patients with wild-type EZH2.

“If we had focused [only] on patients with EZH2 mutations, we would have missed those other complete responders in the wild-type setting,” said study investigator Franck Morschhauser, MD, PhD, of Centre Hospitalier Régional Universitaire de Lille in France.

He presented results of the trial* during the plenary session of the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by Epizyme, the company developing tazemetostat.

The trial enrolled patients with relapsed or refractory DLBCL or FL who had received at least 2 prior therapies. The patients received tazemetostat at 800 mg twice daily until disease progression or study withdrawal.

Efficacy in FL

Dr Morschhauser presented efficacy data on 67 patients with FL. Thirteen had EZH2 mutations, and 54 had wild-type EZH2. The median age was 62 in the mutated group and 61 in the wild-type group.

Both groups had a median of 4 prior lines of therapy. Fifty-four percent of EZH2-mutated patients were refractory to their last treatment, as were 48% of wild-type patients.

The median time from diagnosis was 7.4 years in mutated patients and 4.9 years in wild-type patients. The median time from last therapy was 13 weeks and 41.3 weeks, respectively.

The overall response rate was 92% (12/13) in EZH2-mutated patients and 26% (14/54) in wild-type patients. The complete response rates were 8% (n=1) and 6% (n=3), respectively.

The median time to first response was 11.9 weeks and 15.2 weeks, respectively.

None of the EZH2-mutated patients have progressed, but 13 (24%) wild-type patients have.

Forty-eight percent of all FL patients remain on study. One EZH2-mutated patient with stable disease is still on study, as are 23 wild-type patients with stable disease.

Efficacy in DLBCL

Dr Morschhauser presented data on 137 patients with DLBCL, 17 with EZH2 mutations and 120 with wild-type EZH2. The median age was 61 in the mutated group and 69 in the wild-type group.

Both groups had a median of 3 prior lines of therapy. Eighty-two percent of EZH2-mutated patients were refractory to their last treatment, as were 63% of wild-type patients.

The median time from diagnosis was 1 year in mutated patients and 2 years in wild-type patients. The median time from last therapy was 8.6 weeks and 11.6 weeks, respectively.

The overall response rate was 29% (5/17) in EZH2-mutated patients and 15% (18/119) in wild-type patients. The complete response rates were 0% (n=0) and 8% (n=10), respectively.

The median time to first response was 8.3 weeks and 8.5 weeks, respectively.

Six (35%) of the EZH2-mutated patients have progressed, as have 60 (50%) wild-type patients.

Twelve percent of all DLBCL patients remain on study. One EZH2-mutated patient with stable disease is still on therapy, as are 4 wild-type patients with stable disease.

Predictors of response

Dr Morschhauser and his colleagues performed next-generation sequencing of samples from 92 patients in an attempt to identify predictors of response to tazemetostat.

The data suggested that EZH2 and MYD88 activating mutations are positive predictors of response, and negative predictors include MYC, TP53, and HIST1H1E.

Safety

Safety data were available for 210 patients. The overall rate of treatment-related adverse events (AEs) was 59%, the rate of grade 3 or higher treatment-related AEs was 18%, and the rate of serious treatment-related AEs was 10%.

There were treatment-related AEs leading to dose interruption (15%), dose reduction (3%), and discontinuation of tazemetostat (2%).

The most common treatment-related AEs were nausea (14%), thrombocytopenia (13%), anemia (10%), neutropenia (9%), diarrhea (8%), asthenia (8%), and fatigue (7%).

Dr Morschhauser said these results “confirm that tazemetostat is quite safe” in this patient population, and enrollment in this trial is ongoing. 

*Data in the abstract differ from the presentation.

14th International Conference on Malignant Lymphoma (ICML)

LUGANO, SWITZERLAND—Interim results of a phase 2 trial suggest tazemetostat can be effective in patients with heavily pretreated, relapsed or refractory non-Hodgkin lymphoma.

The EZH2 inhibitor produced the highest overall response rate in patients with EZH2-mutated follicular lymphoma (FL), followed by EZH2-mutated diffuse large B-cell lymphoma (DLBCL).

However, the drug also produced complete responses in FL and DLBCL patients with wild-type EZH2.

“If we had focused [only] on patients with EZH2 mutations, we would have missed those other complete responders in the wild-type setting,” said study investigator Franck Morschhauser, MD, PhD, of Centre Hospitalier Régional Universitaire de Lille in France.

He presented results of the trial* during the plenary session of the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by Epizyme, the company developing tazemetostat.

The trial enrolled patients with relapsed or refractory DLBCL or FL who had received at least 2 prior therapies. The patients received tazemetostat at 800 mg twice daily until disease progression or study withdrawal.

Efficacy in FL

Dr Morschhauser presented efficacy data on 67 patients with FL. Thirteen had EZH2 mutations, and 54 had wild-type EZH2. The median age was 62 in the mutated group and 61 in the wild-type group.

Both groups had a median of 4 prior lines of therapy. Fifty-four percent of EZH2-mutated patients were refractory to their last treatment, as were 48% of wild-type patients.

The median time from diagnosis was 7.4 years in mutated patients and 4.9 years in wild-type patients. The median time from last therapy was 13 weeks and 41.3 weeks, respectively.

The overall response rate was 92% (12/13) in EZH2-mutated patients and 26% (14/54) in wild-type patients. The complete response rates were 8% (n=1) and 6% (n=3), respectively.

The median time to first response was 11.9 weeks and 15.2 weeks, respectively.

None of the EZH2-mutated patients have progressed, but 13 (24%) wild-type patients have.

Forty-eight percent of all FL patients remain on study. One EZH2-mutated patient with stable disease is still on study, as are 23 wild-type patients with stable disease.

Efficacy in DLBCL

Dr Morschhauser presented data on 137 patients with DLBCL, 17 with EZH2 mutations and 120 with wild-type EZH2. The median age was 61 in the mutated group and 69 in the wild-type group.

Both groups had a median of 3 prior lines of therapy. Eighty-two percent of EZH2-mutated patients were refractory to their last treatment, as were 63% of wild-type patients.

The median time from diagnosis was 1 year in mutated patients and 2 years in wild-type patients. The median time from last therapy was 8.6 weeks and 11.6 weeks, respectively.

The overall response rate was 29% (5/17) in EZH2-mutated patients and 15% (18/119) in wild-type patients. The complete response rates were 0% (n=0) and 8% (n=10), respectively.

The median time to first response was 8.3 weeks and 8.5 weeks, respectively.

Six (35%) of the EZH2-mutated patients have progressed, as have 60 (50%) wild-type patients.

Twelve percent of all DLBCL patients remain on study. One EZH2-mutated patient with stable disease is still on therapy, as are 4 wild-type patients with stable disease.

Predictors of response

Dr Morschhauser and his colleagues performed next-generation sequencing of samples from 92 patients in an attempt to identify predictors of response to tazemetostat.

The data suggested that EZH2 and MYD88 activating mutations are positive predictors of response, and negative predictors include MYC, TP53, and HIST1H1E.

Safety

Safety data were available for 210 patients. The overall rate of treatment-related adverse events (AEs) was 59%, the rate of grade 3 or higher treatment-related AEs was 18%, and the rate of serious treatment-related AEs was 10%.

There were treatment-related AEs leading to dose interruption (15%), dose reduction (3%), and discontinuation of tazemetostat (2%).

The most common treatment-related AEs were nausea (14%), thrombocytopenia (13%), anemia (10%), neutropenia (9%), diarrhea (8%), asthenia (8%), and fatigue (7%).

Dr Morschhauser said these results “confirm that tazemetostat is quite safe” in this patient population, and enrollment in this trial is ongoing. 

*Data in the abstract differ from the presentation.

14th International Conference on Malignant Lymphoma (ICML)

LUGANO, SWITZERLAND—Interim results of a phase 2 trial suggest tazemetostat can be effective in patients with heavily pretreated, relapsed or refractory non-Hodgkin lymphoma.

The EZH2 inhibitor produced the highest overall response rate in patients with EZH2-mutated follicular lymphoma (FL), followed by EZH2-mutated diffuse large B-cell lymphoma (DLBCL).

However, the drug also produced complete responses in FL and DLBCL patients with wild-type EZH2.

“If we had focused [only] on patients with EZH2 mutations, we would have missed those other complete responders in the wild-type setting,” said study investigator Franck Morschhauser, MD, PhD, of Centre Hospitalier Régional Universitaire de Lille in France.

He presented results of the trial* during the plenary session of the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by Epizyme, the company developing tazemetostat.

The trial enrolled patients with relapsed or refractory DLBCL or FL who had received at least 2 prior therapies. The patients received tazemetostat at 800 mg twice daily until disease progression or study withdrawal.

Efficacy in FL

Dr Morschhauser presented efficacy data on 67 patients with FL. Thirteen had EZH2 mutations, and 54 had wild-type EZH2. The median age was 62 in the mutated group and 61 in the wild-type group.

Both groups had a median of 4 prior lines of therapy. Fifty-four percent of EZH2-mutated patients were refractory to their last treatment, as were 48% of wild-type patients.

The median time from diagnosis was 7.4 years in mutated patients and 4.9 years in wild-type patients. The median time from last therapy was 13 weeks and 41.3 weeks, respectively.

The overall response rate was 92% (12/13) in EZH2-mutated patients and 26% (14/54) in wild-type patients. The complete response rates were 8% (n=1) and 6% (n=3), respectively.

The median time to first response was 11.9 weeks and 15.2 weeks, respectively.

None of the EZH2-mutated patients have progressed, but 13 (24%) wild-type patients have.

Forty-eight percent of all FL patients remain on study. One EZH2-mutated patient with stable disease is still on study, as are 23 wild-type patients with stable disease.

Efficacy in DLBCL

Dr Morschhauser presented data on 137 patients with DLBCL, 17 with EZH2 mutations and 120 with wild-type EZH2. The median age was 61 in the mutated group and 69 in the wild-type group.

Both groups had a median of 3 prior lines of therapy. Eighty-two percent of EZH2-mutated patients were refractory to their last treatment, as were 63% of wild-type patients.

The median time from diagnosis was 1 year in mutated patients and 2 years in wild-type patients. The median time from last therapy was 8.6 weeks and 11.6 weeks, respectively.

The overall response rate was 29% (5/17) in EZH2-mutated patients and 15% (18/119) in wild-type patients. The complete response rates were 0% (n=0) and 8% (n=10), respectively.

The median time to first response was 8.3 weeks and 8.5 weeks, respectively.

Six (35%) of the EZH2-mutated patients have progressed, as have 60 (50%) wild-type patients.

Twelve percent of all DLBCL patients remain on study. One EZH2-mutated patient with stable disease is still on therapy, as are 4 wild-type patients with stable disease.

Predictors of response

Dr Morschhauser and his colleagues performed next-generation sequencing of samples from 92 patients in an attempt to identify predictors of response to tazemetostat.

The data suggested that EZH2 and MYD88 activating mutations are positive predictors of response, and negative predictors include MYC, TP53, and HIST1H1E.

Safety

Safety data were available for 210 patients. The overall rate of treatment-related adverse events (AEs) was 59%, the rate of grade 3 or higher treatment-related AEs was 18%, and the rate of serious treatment-related AEs was 10%.

There were treatment-related AEs leading to dose interruption (15%), dose reduction (3%), and discontinuation of tazemetostat (2%).

The most common treatment-related AEs were nausea (14%), thrombocytopenia (13%), anemia (10%), neutropenia (9%), diarrhea (8%), asthenia (8%), and fatigue (7%).

Dr Morschhauser said these results “confirm that tazemetostat is quite safe” in this patient population, and enrollment in this trial is ongoing. 

*Data in the abstract differ from the presentation.

Anna Sureda, MD, PhD

In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.

 Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.

Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).

Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.¹ Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.

Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,^2-4 underlining the challenges of treating later stage Hodgkin lymphoma.

Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)^5-6— a historically and frequently used treatment regimen.

These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.^7-10

With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.^8-15

Advanced stage vs early stage Hodgkin lymphoma

Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.^7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,^7,15-16 with nearly one third remaining uncured following standard frontline therapy.^7-10

As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.¹⁶

The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.¹⁶

 Unmet needs with current frontline Hodgkin lymphoma treatment

 Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.

ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.¹⁷

Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.^8-10,13,18

Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.¹⁹

Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.^8-10,13-15

 Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,²⁰ is also associated with an increased risk of secondary cancers and cardiotoxicity.^8-10,21

With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.

For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.^{8-10,12-15,22}

Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.^23-25 These secondary effects can affect a patient’s quality of life^{8-9,12,14-15,22,26-28}  and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.²²

Studies have shown that most relapses after ASCT typically occur within 2 years.²⁹ After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.^22,26,30

 Goals of clinical research

Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.^7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.

Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities. 

 Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

______________________________________________________

¹American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.

²Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

³American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.

⁴Fermé C, et al. New Engl J Med, 2007.357:1916–27.

⁵Sureda A, et al. Ann Oncol, 2005;16: 625–633.

⁶Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.

⁷Gordon LI, et al. J Clin Oncol, 2013;31:684-691.

⁸Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.

⁹Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554

¹⁰Viviani S, et al. New Engl J Med, 2011;365(3):203-212.

¹¹Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232

¹²Behringer K, et al. J Clin Oncol, 2013;31:231-239.

¹³Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.

¹⁴Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.

¹⁵Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.

¹⁶Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260

¹⁷Ansell SM. American Journal of Hematology, 2014;89: 771–779.

¹⁸Merli F, et al. J Clin Oncol, 34:1175-1181.

¹⁹Johnson P, et al. N Engl J Med. 2016;3‌74:24‌19‑24‌29

²⁰American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.

²¹Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.

²²Khimani N, et al. Ann Oncol, 2013;24(1):226-230.

²³Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.

²⁴Evens AM, et al. Br J Haematol, 2013;161: 76–86.

²⁵Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.

²⁶Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.

²⁷Daniels LA, et al. Br J Cancer 2014;110:868-874.

²⁸Loge JH, et al. Ann Oncol. 1999;10:71-77.

²⁹Brusamolino E, Carella AM. Haematologica, 2007;92:6-10

³⁰Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.

Anna Sureda, MD, PhD

In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.

 Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.

Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).

Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.¹ Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.

Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,^2-4 underlining the challenges of treating later stage Hodgkin lymphoma.

Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)^5-6— a historically and frequently used treatment regimen.

These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.^7-10

With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.^8-15

Advanced stage vs early stage Hodgkin lymphoma

Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.^7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,^7,15-16 with nearly one third remaining uncured following standard frontline therapy.^7-10

As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.¹⁶

The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.¹⁶

 Unmet needs with current frontline Hodgkin lymphoma treatment

 Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.

ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.¹⁷

Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.^8-10,13,18

Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.¹⁹

Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.^8-10,13-15

 Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,²⁰ is also associated with an increased risk of secondary cancers and cardiotoxicity.^8-10,21

With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.

For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.^{8-10,12-15,22}

Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.^23-25 These secondary effects can affect a patient’s quality of life^{8-9,12,14-15,22,26-28}  and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.²²

Studies have shown that most relapses after ASCT typically occur within 2 years.²⁹ After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.^22,26,30

 Goals of clinical research

Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.^7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.

Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities. 

 Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

______________________________________________________

¹American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.

²Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

³American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.

⁴Fermé C, et al. New Engl J Med, 2007.357:1916–27.

⁵Sureda A, et al. Ann Oncol, 2005;16: 625–633.

⁶Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.

⁷Gordon LI, et al. J Clin Oncol, 2013;31:684-691.

⁸Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.

⁹Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554

¹⁰Viviani S, et al. New Engl J Med, 2011;365(3):203-212.

¹¹Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232

¹²Behringer K, et al. J Clin Oncol, 2013;31:231-239.

¹³Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.

¹⁴Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.

¹⁵Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.

¹⁶Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260

¹⁷Ansell SM. American Journal of Hematology, 2014;89: 771–779.

¹⁸Merli F, et al. J Clin Oncol, 34:1175-1181.

¹⁹Johnson P, et al. N Engl J Med. 2016;3‌74:24‌19‑24‌29

²⁰American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.

²¹Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.

²²Khimani N, et al. Ann Oncol, 2013;24(1):226-230.

²³Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.

²⁴Evens AM, et al. Br J Haematol, 2013;161: 76–86.

²⁵Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.

²⁶Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.

²⁷Daniels LA, et al. Br J Cancer 2014;110:868-874.

²⁸Loge JH, et al. Ann Oncol. 1999;10:71-77.

²⁹Brusamolino E, Carella AM. Haematologica, 2007;92:6-10

³⁰Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.

Anna Sureda, MD, PhD

In this editorial, Anna Sureda, MD, PhD, details the need for new frontline treatments for patients with Hodgkin lymphoma, including those with advanced stage disease.

 Dr Sureda is head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme at the Institut Català d'Oncologia, Hospital Duran i Reynals, in Barcelona, Spain. She has received consultancy fees from Takeda/Millennium Pharmaceuticals, Merck Sharp & Dohme, and Bristol-Myers Squibb.

Hodgkin lymphoma has traditionally been known as a cancer with generally favorable outcomes. Yet, as with any cancer treatment, there is always room for improvement. For Hodgkin lymphoma specifically, there remains a significant unmet need in the frontline setting for patients with advanced disease (Stage III or Stage IV).

Hodgkin lymphoma most commonly affects young adults as well as adults over the age of 55.¹ Both age at diagnosis and stage of the disease are significant factors that must be considered when determining treatment plans, as they can affect a patient’s success in achieving long-term remission.

Though early stage patients have demonstrated 5-year survival rates of approximately 90%, this number drops to 70% in patients with advanced stage disease,^2-4 underlining the challenges of treating later stage Hodgkin lymphoma.

Additionally, only 50% of patients with relapsed or refractory disease will experience long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT)^5-6— a historically and frequently used treatment regimen.

These facts support the importance of successful frontline treatment and highlight a gap with current treatment regimens.^7-10

With current frontline Hodgkin lymphoma treatments, it can be a challenge for physicians to balance efficacy with safety. While allowing the patient to achieve long-term remission remains the goal, physicians are also considering the impact of treatment-related side effects including endocrine dysfunction, cardiac dysfunction, lung toxicity, infertility, and an increased risk of secondary cancers when determining the best possible treatment.^8-15

Advanced stage vs early stage Hodgkin lymphoma

Stage of disease at diagnosis has a large influence on outcomes, with advanced stage patients having poorer outcomes than earlier stage patients.^7,15-16 Advanced Hodgkin lymphoma patients are more likely to progress or relapse,^7,15-16 with nearly one third remaining uncured following standard frontline therapy.^7-10

As seen in Figure 1 below, there is a clear difference in progression-free survival for early versus advanced stage Hodgkin lymphoma.¹⁶

The difference between early stage and advanced stage patients treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) demonstrates the heightened importance of successful frontline treatment for those with advanced stage disease.¹⁶

 Unmet needs with current frontline Hodgkin lymphoma treatment

 Though current treatments for frontline Hodgkin lymphoma, including ABVD and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), have improved outcomes for patients, these standard regimens are more than 20 years old.

ABVD is generally regarded as the treatment of choice based on its efficacy, relative ease of administration, and side effect profile.¹⁷

Escalated BEACOPP, on the other hand, was developed to improve outcomes for advanced stage patients but is associated with increased toxicity.^8-10,13,18

Positron emission tomography (PET) scans have also been identified as a pathway to help guide further treatment, but patients with advanced stage Hodgkin lymphoma may relapse more often, despite a negative interim PET scan, compared to stage II patients.¹⁹

Among current treatments, side effects including lung and cardiotoxicity as well as an increased risk of secondary cancers are a concern for both physicians and their patients.^8-10,13-15

 Similarly, radiation therapy, often used in conjunction with chemotherapy for patients who have a large tumor burden in one part of the body, usually the chest,²⁰ is also associated with an increased risk of secondary cancers and cardiotoxicity.^8-10,21

With these complications in mind, stabilizing the effects between improved efficacy and minimizing the toxicities associated with current frontline treatments needs to be a focus as new therapies are developed.

For young patients specifically, minimizing toxicities is crucial, as many will have a lifetime ahead of them after Hodgkin lymphoma and will want to avoid the risks associated with current treatments including lung disease, heart disease and infertility.^{8-10,12-15,22}

Treating elderly patients can also be challenging due to their reduced ability to tolerate aggressive frontline treatment and multi-agent chemotherapy, which causes inferior survival outcomes when compared to younger patients.^23-25 These secondary effects can affect a patient’s quality of life^{8-9,12,14-15,22,26-28}  and exacerbate preexisting conditions commonly experienced by those undergoing treatment, including long-term fatigue, chronic medical and psychosocial complications, and general deterioration in physical well-being.²²

Studies have shown that most relapses after ASCT typically occur within 2 years.²⁹ After a relapse, the patient may endure a substantial physical and psychological burden due to the need for additional treatment, impacting quality of life for both the patient and their caregiver.^22,26,30

 Goals of clinical research

Despite its recognition as a highly treatable cancer, newly diagnosed Hodgkin lymphoma remains incurable in up to 30% of patients with advanced disease.^7-10 Though current therapies seek to achieve remission and extend the lives of patients, it is often at the cost of treatment-related toxicities and side effects that can significantly reduce quality of life.

Moving forward, it is critical that these gaps in treatment are addressed in new frontline treatments that aim to benefit patients, including those with advanced stage disease, while reducing short-term and long-term toxicities. 

 Acknowledgements: The author would like to acknowledge the W2O Group for their writing support, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

______________________________________________________

¹American Cancer Society. What Are the Key Statistics About Hodgkin Disease? https://www.cancer.org/cancer/hodgkin-lymphoma/about/key-statistics.html. Accessed February 16, 2017.

²Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (editors). SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988-2001, Patient and Tumor Characteristics. National Cancer Institute, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD, 2007.

³American Cancer Society. Survival Rates for Hodgkin Disease by Stage. https://www.cancer.org/cancer/hodgkin-lymphoma/detection-diagnosis-staging/survival-rates.html. Accessed February 16, 2017.

⁴Fermé C, et al. New Engl J Med, 2007.357:1916–27.

⁵Sureda A, et al. Ann Oncol, 2005;16: 625–633.

⁶Majhail NS, et al. Biol Blood Marrow Transplant, 2006;12:1065–1072.

⁷Gordon LI, et al. J Clin Oncol, 2013;31:684-691.

⁸Carde P, et al. J Clin Oncol, 2016;34(17):2028-2036.

⁹Engert A, et al. J Clin Oncol, 2009;27(27):4548-4554

¹⁰Viviani S, et al. New Engl J Med, 2011;365(3):203-212.

¹¹Sklar C, et al. J Endocrinology & Metabolism, 2000;85(9):3227-3232

¹²Behringer K, et al. J Clin Oncol, 2013;31:231-239.

¹³Borchmann P, et al. J Clin Oncol, 2011;29(32):4234-4242.

¹⁴Duggan DB, et al. J Clin Oncol, 2003;21(4):607-614.

¹⁵Johnson P, McKenzie H. Blood, 2015;125(11):1717-1723.

¹⁶Maddi RN, et al. Indian J Medical and Paediatric Oncology, 2015;36(4):255-260

¹⁷Ansell SM. American Journal of Hematology, 2014;89: 771–779.

¹⁸Merli F, et al. J Clin Oncol, 34:1175-1181.

¹⁹Johnson P, et al. N Engl J Med. 2016;3‌74:24‌19‑24‌29

²⁰American Cancer Society. Treating Hodgkin Disease: Radiation Therapy for Hodgkin Disease. https://www.cancer.org/cancer/hodgkin-lymphoma/treating/radiation.html. Accessed January 30, 2017.

²¹Adams MJ, et al. J Clin Oncol, 2004; 22: 3139–48.

²²Khimani N, et al. Ann Oncol, 2013;24(1):226-230.

²³Engert A, et al. J Clin Oncol, 2005;23(22):5052-60.

²⁴Evens AM, et al. Br J Haematol, 2013;161: 76–86.

²⁵Janssen-Heijnen ML, et al. Br J Haematol, 2005;129:597-606.

²⁶Ganz PA et al. J Clin Oncol, 2003;21(18):3512-3519.

²⁷Daniels LA, et al. Br J Cancer 2014;110:868-874.

²⁸Loge JH, et al. Ann Oncol. 1999;10:71-77.

²⁹Brusamolino E, Carella AM. Haematologica, 2007;92:6-10

³⁰Consolidation Therapy After ASCT in Hodgkin Lymphoma: Why and Who to Treat? Personalized Medicine in Oncology, 2016. http://www.personalizedmedonc.com/article/consolidation-therapy-after-asct-in-hodgkin-lymphoma-why-and-who-to-treat/. Accessed February 16, 2017.

Fewer teens were having sex in 2011-2015, compared with past years, and contraception use increased among both male and female teens, according to a report by Joyce C. Abma, PhD, and Gladys M. Martinez, PhD, of the Division of Vital Statistics at the National Center for Health Statistics, Hyattsville, Md.

The percentage of female teens who had ever had sexual intercourse declined from 51% in 1988 to 42% in 2011-2015. For male teens, the percentage who were sexually experienced declined from 60% in 1988 to 44% in 2011-2015.

©Florea Marius Catalin/iStockphoto.com

Fewer teens were having sex in 2011-2015, compared with past years, and contraception use increased among both male and female teens, according to a report by Joyce C. Abma, PhD, and Gladys M. Martinez, PhD, of the Division of Vital Statistics at the National Center for Health Statistics, Hyattsville, Md.

The percentage of female teens who had ever had sexual intercourse declined from 51% in 1988 to 42% in 2011-2015. For male teens, the percentage who were sexually experienced declined from 60% in 1988 to 44% in 2011-2015.

©Florea Marius Catalin/iStockphoto.com

Fewer teens were having sex in 2011-2015, compared with past years, and contraception use increased among both male and female teens, according to a report by Joyce C. Abma, PhD, and Gladys M. Martinez, PhD, of the Division of Vital Statistics at the National Center for Health Statistics, Hyattsville, Md.

The percentage of female teens who had ever had sexual intercourse declined from 51% in 1988 to 42% in 2011-2015. For male teens, the percentage who were sexually experienced declined from 60% in 1988 to 44% in 2011-2015.

©Florea Marius Catalin/iStockphoto.com

The FP suspected that this was a case of dermatographism. To confirm his suspicions, he used the end of a cotton-tipped applicator and wrote on the patient’s skin. Within 3 minutes, the writing turned into a triple reaction with some erythema, blanching, and swelling—confirming the diagnosis.

Dermatographism often accompanies urticaria, but can occur without it. If one writes on the skin, one is able to see the resulting words or shapes. The cause of this condition is unknown, but the pathophysiology involves degranulation of mast cells and the release of histamine.

No treatment is required for asymptomatic dermatographism. If patients are symptomatic, they should be advised to avoid precipitating physical stimuli. Dry skin may stimulate scratching, so the use of emollients can help. If the patient wants a medication, start with a second-generation antihistamine such as loratadine or cetirizine. While the recommended over-the-counter dose of these 2 medications is 10 mg/d, the dose may be increased to 20 mg twice daily. It is best to start at the lowest dose and then titrate up according to response and tolerance of adverse effects. (The second-generation antihistamines can still be sedating.) If this doesn’t work, a sedating antihistamine can be added before bedtime.

Dermatographism is not life-threatening and does not lead to anaphylaxis. The patient in this case didn’t want treatment and was pleased to know what was going on with his skin.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Urticaria and angioedema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 863-870.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected that this was a case of dermatographism. To confirm his suspicions, he used the end of a cotton-tipped applicator and wrote on the patient’s skin. Within 3 minutes, the writing turned into a triple reaction with some erythema, blanching, and swelling—confirming the diagnosis.

Dermatographism often accompanies urticaria, but can occur without it. If one writes on the skin, one is able to see the resulting words or shapes. The cause of this condition is unknown, but the pathophysiology involves degranulation of mast cells and the release of histamine.

No treatment is required for asymptomatic dermatographism. If patients are symptomatic, they should be advised to avoid precipitating physical stimuli. Dry skin may stimulate scratching, so the use of emollients can help. If the patient wants a medication, start with a second-generation antihistamine such as loratadine or cetirizine. While the recommended over-the-counter dose of these 2 medications is 10 mg/d, the dose may be increased to 20 mg twice daily. It is best to start at the lowest dose and then titrate up according to response and tolerance of adverse effects. (The second-generation antihistamines can still be sedating.) If this doesn’t work, a sedating antihistamine can be added before bedtime.

Dermatographism is not life-threatening and does not lead to anaphylaxis. The patient in this case didn’t want treatment and was pleased to know what was going on with his skin.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Urticaria and angioedema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 863-870.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected that this was a case of dermatographism. To confirm his suspicions, he used the end of a cotton-tipped applicator and wrote on the patient’s skin. Within 3 minutes, the writing turned into a triple reaction with some erythema, blanching, and swelling—confirming the diagnosis.

Dermatographism often accompanies urticaria, but can occur without it. If one writes on the skin, one is able to see the resulting words or shapes. The cause of this condition is unknown, but the pathophysiology involves degranulation of mast cells and the release of histamine.

No treatment is required for asymptomatic dermatographism. If patients are symptomatic, they should be advised to avoid precipitating physical stimuli. Dry skin may stimulate scratching, so the use of emollients can help. If the patient wants a medication, start with a second-generation antihistamine such as loratadine or cetirizine. While the recommended over-the-counter dose of these 2 medications is 10 mg/d, the dose may be increased to 20 mg twice daily. It is best to start at the lowest dose and then titrate up according to response and tolerance of adverse effects. (The second-generation antihistamines can still be sedating.) If this doesn’t work, a sedating antihistamine can be added before bedtime.

Dermatographism is not life-threatening and does not lead to anaphylaxis. The patient in this case didn’t want treatment and was pleased to know what was going on with his skin.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Urticaria and angioedema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 863-870.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Chronic liver disease appears to double the risk of colorectal cancer (CRC), even after patients undergo liver transplantation, according to a report published in Gastrointestinal Endoscopy.

“Strict surveillance for colorectal cancer is warranted in this patient population,” said Yuga Komaki, MD, of the section of gastroenterology, hepatology, and nutrition, University of Chicago, and associates.

One prominent chronic liver disease, primary sclerosing cholangitis, is known to raise the risk of CRC, which “is mainly attributed to the concurrence of inflammatory bowel disease.” In addition, whether liver transplantation mitigates that risk remains “controversial,” the investigators noted.

To assess whether chronic liver disease impacts CRC risk, they performed a systematic review and meta-analysis of the literature, examining data from 55 observational studies involving 55,991 participants. Case patients had a variety of chronic liver diseases, including primary sclerosing cholangitis, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver damage.

Overall, the pooled standardized incidence ratio of CRC was 2.06 among patients with liver disease, compared with control subjects. It was highest in the subgroup of patients with primary sclerosing cholangitis at 6.70, the investigators said (Gastrointest. Endosc. 2017;86:93-104).

CRC risk appeared to be slightly higher among patients who had cirrhosis than among those who had hepatitis, “suggesting that advanced liver damage may lead to higher risks of CRC. This is not surprising because advanced liver damage can cause systemic alterations in immunity that may precipitate malignant transformation,” Dr. Komaki and associates noted.

The pooled standardized incidence ratio of CRC remained elevated at 2.16 among patients who underwent liver transplantation for a variety of causes. It is possible that their exposure to immunosuppressive therapy plays a role in elevating this risk, the researchers added.

“We propose that patients with chronic hepatitis and cirrhosis require a screening colonoscopy every 5 years, as opposed to the 10-year interval in the general population. Patients undergoing liver transplant should have a colonoscopy before the transplant and, subsequently, should undergo colonoscopy at 5-year intervals,” Dr. Komaki and associates said.

They added that the sixfold increase in CRC risk among patients with PSC “justifies the present recommendation of annual surveillance colonoscopy that should be continued after transplant.”

Chronic liver disease appears to double the risk of colorectal cancer (CRC), even after patients undergo liver transplantation, according to a report published in Gastrointestinal Endoscopy.

“Strict surveillance for colorectal cancer is warranted in this patient population,” said Yuga Komaki, MD, of the section of gastroenterology, hepatology, and nutrition, University of Chicago, and associates.

One prominent chronic liver disease, primary sclerosing cholangitis, is known to raise the risk of CRC, which “is mainly attributed to the concurrence of inflammatory bowel disease.” In addition, whether liver transplantation mitigates that risk remains “controversial,” the investigators noted.

To assess whether chronic liver disease impacts CRC risk, they performed a systematic review and meta-analysis of the literature, examining data from 55 observational studies involving 55,991 participants. Case patients had a variety of chronic liver diseases, including primary sclerosing cholangitis, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver damage.

Overall, the pooled standardized incidence ratio of CRC was 2.06 among patients with liver disease, compared with control subjects. It was highest in the subgroup of patients with primary sclerosing cholangitis at 6.70, the investigators said (Gastrointest. Endosc. 2017;86:93-104).

CRC risk appeared to be slightly higher among patients who had cirrhosis than among those who had hepatitis, “suggesting that advanced liver damage may lead to higher risks of CRC. This is not surprising because advanced liver damage can cause systemic alterations in immunity that may precipitate malignant transformation,” Dr. Komaki and associates noted.

The pooled standardized incidence ratio of CRC remained elevated at 2.16 among patients who underwent liver transplantation for a variety of causes. It is possible that their exposure to immunosuppressive therapy plays a role in elevating this risk, the researchers added.

“We propose that patients with chronic hepatitis and cirrhosis require a screening colonoscopy every 5 years, as opposed to the 10-year interval in the general population. Patients undergoing liver transplant should have a colonoscopy before the transplant and, subsequently, should undergo colonoscopy at 5-year intervals,” Dr. Komaki and associates said.

They added that the sixfold increase in CRC risk among patients with PSC “justifies the present recommendation of annual surveillance colonoscopy that should be continued after transplant.”

Chronic liver disease appears to double the risk of colorectal cancer (CRC), even after patients undergo liver transplantation, according to a report published in Gastrointestinal Endoscopy.

“Strict surveillance for colorectal cancer is warranted in this patient population,” said Yuga Komaki, MD, of the section of gastroenterology, hepatology, and nutrition, University of Chicago, and associates.

One prominent chronic liver disease, primary sclerosing cholangitis, is known to raise the risk of CRC, which “is mainly attributed to the concurrence of inflammatory bowel disease.” In addition, whether liver transplantation mitigates that risk remains “controversial,” the investigators noted.

To assess whether chronic liver disease impacts CRC risk, they performed a systematic review and meta-analysis of the literature, examining data from 55 observational studies involving 55,991 participants. Case patients had a variety of chronic liver diseases, including primary sclerosing cholangitis, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver damage.

Overall, the pooled standardized incidence ratio of CRC was 2.06 among patients with liver disease, compared with control subjects. It was highest in the subgroup of patients with primary sclerosing cholangitis at 6.70, the investigators said (Gastrointest. Endosc. 2017;86:93-104).

CRC risk appeared to be slightly higher among patients who had cirrhosis than among those who had hepatitis, “suggesting that advanced liver damage may lead to higher risks of CRC. This is not surprising because advanced liver damage can cause systemic alterations in immunity that may precipitate malignant transformation,” Dr. Komaki and associates noted.

The pooled standardized incidence ratio of CRC remained elevated at 2.16 among patients who underwent liver transplantation for a variety of causes. It is possible that their exposure to immunosuppressive therapy plays a role in elevating this risk, the researchers added.

“We propose that patients with chronic hepatitis and cirrhosis require a screening colonoscopy every 5 years, as opposed to the 10-year interval in the general population. Patients undergoing liver transplant should have a colonoscopy before the transplant and, subsequently, should undergo colonoscopy at 5-year intervals,” Dr. Komaki and associates said.

They added that the sixfold increase in CRC risk among patients with PSC “justifies the present recommendation of annual surveillance colonoscopy that should be continued after transplant.”

The U.S. Supreme Court has ruled that biosimilar companies can take their versions of biological drugs to the market 6 months sooner in a precedential ruling that could mean quicker access to less expensive medications.

The unanimous ruling overturns an appeals court ruling in favor of California-based Amgen that had barred competitor Sandoz from marketing its biosimilar of Neupogen (filgrastim) until 6 months after Food and Drug Administration approval. Justices held that the Biologics Price Competition and Innovation Act of 2009 (BPCIA) allows biosimilar applicants to provide notice of commercial marketing prior to obtaining licensure by the FDA.

Carol Lynch, global head of Biopharmaceuticals at Sandoz, said the ruling helps to eliminate unnecessary barriers so that patients can access more affordable medicine in a more timely manner.

“Biosimilars offer significant value to patients, providers, and payers, increasing the number of treatment options available to patients across many disease areas at a reduced cost to the health care system,” Ms. Lynch said in a statement. “The justices’ unanimous ruling on the notice of commercial marketing will help expedite patient access to life-enhancing treatments. We also appreciate the clarity provided on the patent dance, which will help the biosimilars industry move forward.”

Gregory Twachtman/Frontline Medical Media

agallegos@frontlinemedcom.com On Twitter @legal_med

AGA Resource

AGA offers education materials for health care professionals and patients at www.gastro.org/biosimilars.  

The U.S. Supreme Court has ruled that biosimilar companies can take their versions of biological drugs to the market 6 months sooner in a precedential ruling that could mean quicker access to less expensive medications.

The unanimous ruling overturns an appeals court ruling in favor of California-based Amgen that had barred competitor Sandoz from marketing its biosimilar of Neupogen (filgrastim) until 6 months after Food and Drug Administration approval. Justices held that the Biologics Price Competition and Innovation Act of 2009 (BPCIA) allows biosimilar applicants to provide notice of commercial marketing prior to obtaining licensure by the FDA.

Carol Lynch, global head of Biopharmaceuticals at Sandoz, said the ruling helps to eliminate unnecessary barriers so that patients can access more affordable medicine in a more timely manner.

“Biosimilars offer significant value to patients, providers, and payers, increasing the number of treatment options available to patients across many disease areas at a reduced cost to the health care system,” Ms. Lynch said in a statement. “The justices’ unanimous ruling on the notice of commercial marketing will help expedite patient access to life-enhancing treatments. We also appreciate the clarity provided on the patent dance, which will help the biosimilars industry move forward.”

Gregory Twachtman/Frontline Medical Media

agallegos@frontlinemedcom.com On Twitter @legal_med

AGA Resource

AGA offers education materials for health care professionals and patients at www.gastro.org/biosimilars.  

The U.S. Supreme Court has ruled that biosimilar companies can take their versions of biological drugs to the market 6 months sooner in a precedential ruling that could mean quicker access to less expensive medications.

The unanimous ruling overturns an appeals court ruling in favor of California-based Amgen that had barred competitor Sandoz from marketing its biosimilar of Neupogen (filgrastim) until 6 months after Food and Drug Administration approval. Justices held that the Biologics Price Competition and Innovation Act of 2009 (BPCIA) allows biosimilar applicants to provide notice of commercial marketing prior to obtaining licensure by the FDA.

Carol Lynch, global head of Biopharmaceuticals at Sandoz, said the ruling helps to eliminate unnecessary barriers so that patients can access more affordable medicine in a more timely manner.

“Biosimilars offer significant value to patients, providers, and payers, increasing the number of treatment options available to patients across many disease areas at a reduced cost to the health care system,” Ms. Lynch said in a statement. “The justices’ unanimous ruling on the notice of commercial marketing will help expedite patient access to life-enhancing treatments. We also appreciate the clarity provided on the patent dance, which will help the biosimilars industry move forward.”

Gregory Twachtman/Frontline Medical Media

agallegos@frontlinemedcom.com On Twitter @legal_med

AGA Resource

AGA offers education materials for health care professionals and patients at www.gastro.org/biosimilars.