Lichenoid dermatoses are a heterogeneous group of diseases with varying clinical presentations. The term “lichenoid” refers to the popular lesions of certain skin disorders of which lichen planus (LP) is the prototype. The papules are shiny, flat topped, polygonal, of different sizes, and occur in clusters creating a pattern that resembles lichen growing on a rock. Lichenoid eruptions are quite common in children and can result from many different origins. In most instances the precise mechanism of disease is not known, although it is usually believed to be immunologic in nature. Certain disorders are common in children, whereas others more often affect the adult population.

Lichen striatus, lichen nitidus (LN), and lichen spinulosus are lichenoid lesions that are more common in children than adults.

LN – as seen in the patient described here – is an uncommon benign inflammatory skin disease, primarily of children. Individual lesions are sharply demarcated, pinpoint to pinhead sized, round or polygonal, and strikingly monomorphous in nature. The papules are usually flesh colored, however, the color varies from yellow and brown to violet hues depending on the background color of the patient’s skin. This variation in color is in contrast with LP which is characteristically violaceous. The surfaces of the papules are flat, shiny, and slightly elevated. They may have a fine scale or a hyperkeratotic plug. The lesions tend to occur in groups, primarily on the abdomen, chest, glans penis, and upper extremities. The Koebner phenomenon is observed and is a hallmark for the disorder. LN is generally asymptomatic, unlike LP, which is exceedingly pruritic.

The cause of LN is unknown; however, it has been proposed that LN, in particular generalized LN, may be associated with immune alterations in the patient. The course of LN is slowly progressive with a tendency toward remission. The lesions can remain stationary for years; however, they sometimes disappear spontaneously and completely.

The differential diagnosis of LN beyond the entities discussed above includes frictional lichenoid eruption, lichenoid drug eruption, LP, and keratosis pilaris.

LP is the classic lichenoid eruption. It is rare in children and occurs most frequently in individuals aged 30-60 years. LP usually manifests as an extremely pruritic eruption of flat-topped polygonal and violaceous papules that often have fine linear white scales known as Wickham striae. The distribution is usually bilateral and symmetric with most of the papules and plaques located on the legs, flexor wrists, neck, and genitalia. The lesions may exhibit the Koebner phenomenon, appearing in a linear pattern along the site of a scratch. Generally, in childhood cases there is reported itching, and oral and nail lesions are less common.

Frictional lichenoid eruption occurs in childhood. The lesions consist of lichenoid papules with regular borders 1-2 mm in diameter that generally are asymptomatic, although they may be mildly pruritic. The papules are found in a very characteristic distribution with almost exclusive involvement of the backs of the hands, fingers, elbows, and knees with occasional involvement of the extensor forearms and cheeks. This disorder occurs in predisposed children who have been exposed to significant frictional force during play, and typically resolves spontaneously after removal of the stimulus.

Keratosis pilaris is a rash that usually is found on the outer areas of the upper arms, upper thighs, buttocks, and cheeks. It consists of small bumps that are flesh colored to red. The bumps generally don’t hurt or itch.

The lack of symptoms and spontaneous healing have rendered treatment unnecessary in most cases. LN generally is self-limiting, thus treatment may not be necessary. However, topical treatment with mid- to high-potency corticosteroids has hastened resolution of lesions in some children, as have topical dinitrochlorobenzene and systemic treatment with psoralens, astemizole, etretinate, and psoralen-UVA.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Neither Dr. Eichenfield nor Dr. Bhatti has any relevant financial disclosures. Email them at pdnews@mdedge.com.

References

Pickert A. Cutis. 2012 Sep;90(3):E1-3. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/Document/September-2017/0900300E1.pdf Tziotzios C et al. J Am Acad Dermatol. 2018 Nov;79(5):789-804. Tilly JJ et al. J Am Acad Dermatol. 2004 Oct;51(4):606-24.

Lichenoid dermatoses are a heterogeneous group of diseases with varying clinical presentations. The term “lichenoid” refers to the popular lesions of certain skin disorders of which lichen planus (LP) is the prototype. The papules are shiny, flat topped, polygonal, of different sizes, and occur in clusters creating a pattern that resembles lichen growing on a rock. Lichenoid eruptions are quite common in children and can result from many different origins. In most instances the precise mechanism of disease is not known, although it is usually believed to be immunologic in nature. Certain disorders are common in children, whereas others more often affect the adult population.

Lichen striatus, lichen nitidus (LN), and lichen spinulosus are lichenoid lesions that are more common in children than adults.

LN – as seen in the patient described here – is an uncommon benign inflammatory skin disease, primarily of children. Individual lesions are sharply demarcated, pinpoint to pinhead sized, round or polygonal, and strikingly monomorphous in nature. The papules are usually flesh colored, however, the color varies from yellow and brown to violet hues depending on the background color of the patient’s skin. This variation in color is in contrast with LP which is characteristically violaceous. The surfaces of the papules are flat, shiny, and slightly elevated. They may have a fine scale or a hyperkeratotic plug. The lesions tend to occur in groups, primarily on the abdomen, chest, glans penis, and upper extremities. The Koebner phenomenon is observed and is a hallmark for the disorder. LN is generally asymptomatic, unlike LP, which is exceedingly pruritic.

The cause of LN is unknown; however, it has been proposed that LN, in particular generalized LN, may be associated with immune alterations in the patient. The course of LN is slowly progressive with a tendency toward remission. The lesions can remain stationary for years; however, they sometimes disappear spontaneously and completely.

The differential diagnosis of LN beyond the entities discussed above includes frictional lichenoid eruption, lichenoid drug eruption, LP, and keratosis pilaris.

LP is the classic lichenoid eruption. It is rare in children and occurs most frequently in individuals aged 30-60 years. LP usually manifests as an extremely pruritic eruption of flat-topped polygonal and violaceous papules that often have fine linear white scales known as Wickham striae. The distribution is usually bilateral and symmetric with most of the papules and plaques located on the legs, flexor wrists, neck, and genitalia. The lesions may exhibit the Koebner phenomenon, appearing in a linear pattern along the site of a scratch. Generally, in childhood cases there is reported itching, and oral and nail lesions are less common.

Frictional lichenoid eruption occurs in childhood. The lesions consist of lichenoid papules with regular borders 1-2 mm in diameter that generally are asymptomatic, although they may be mildly pruritic. The papules are found in a very characteristic distribution with almost exclusive involvement of the backs of the hands, fingers, elbows, and knees with occasional involvement of the extensor forearms and cheeks. This disorder occurs in predisposed children who have been exposed to significant frictional force during play, and typically resolves spontaneously after removal of the stimulus.

Keratosis pilaris is a rash that usually is found on the outer areas of the upper arms, upper thighs, buttocks, and cheeks. It consists of small bumps that are flesh colored to red. The bumps generally don’t hurt or itch.

The lack of symptoms and spontaneous healing have rendered treatment unnecessary in most cases. LN generally is self-limiting, thus treatment may not be necessary. However, topical treatment with mid- to high-potency corticosteroids has hastened resolution of lesions in some children, as have topical dinitrochlorobenzene and systemic treatment with psoralens, astemizole, etretinate, and psoralen-UVA.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Neither Dr. Eichenfield nor Dr. Bhatti has any relevant financial disclosures. Email them at pdnews@mdedge.com.

References

Pickert A. Cutis. 2012 Sep;90(3):E1-3. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/Document/September-2017/0900300E1.pdf Tziotzios C et al. J Am Acad Dermatol. 2018 Nov;79(5):789-804. Tilly JJ et al. J Am Acad Dermatol. 2004 Oct;51(4):606-24.

Lichenoid dermatoses are a heterogeneous group of diseases with varying clinical presentations. The term “lichenoid” refers to the popular lesions of certain skin disorders of which lichen planus (LP) is the prototype. The papules are shiny, flat topped, polygonal, of different sizes, and occur in clusters creating a pattern that resembles lichen growing on a rock. Lichenoid eruptions are quite common in children and can result from many different origins. In most instances the precise mechanism of disease is not known, although it is usually believed to be immunologic in nature. Certain disorders are common in children, whereas others more often affect the adult population.

Lichen striatus, lichen nitidus (LN), and lichen spinulosus are lichenoid lesions that are more common in children than adults.

LN – as seen in the patient described here – is an uncommon benign inflammatory skin disease, primarily of children. Individual lesions are sharply demarcated, pinpoint to pinhead sized, round or polygonal, and strikingly monomorphous in nature. The papules are usually flesh colored, however, the color varies from yellow and brown to violet hues depending on the background color of the patient’s skin. This variation in color is in contrast with LP which is characteristically violaceous. The surfaces of the papules are flat, shiny, and slightly elevated. They may have a fine scale or a hyperkeratotic plug. The lesions tend to occur in groups, primarily on the abdomen, chest, glans penis, and upper extremities. The Koebner phenomenon is observed and is a hallmark for the disorder. LN is generally asymptomatic, unlike LP, which is exceedingly pruritic.

The cause of LN is unknown; however, it has been proposed that LN, in particular generalized LN, may be associated with immune alterations in the patient. The course of LN is slowly progressive with a tendency toward remission. The lesions can remain stationary for years; however, they sometimes disappear spontaneously and completely.

The differential diagnosis of LN beyond the entities discussed above includes frictional lichenoid eruption, lichenoid drug eruption, LP, and keratosis pilaris.

LP is the classic lichenoid eruption. It is rare in children and occurs most frequently in individuals aged 30-60 years. LP usually manifests as an extremely pruritic eruption of flat-topped polygonal and violaceous papules that often have fine linear white scales known as Wickham striae. The distribution is usually bilateral and symmetric with most of the papules and plaques located on the legs, flexor wrists, neck, and genitalia. The lesions may exhibit the Koebner phenomenon, appearing in a linear pattern along the site of a scratch. Generally, in childhood cases there is reported itching, and oral and nail lesions are less common.

Frictional lichenoid eruption occurs in childhood. The lesions consist of lichenoid papules with regular borders 1-2 mm in diameter that generally are asymptomatic, although they may be mildly pruritic. The papules are found in a very characteristic distribution with almost exclusive involvement of the backs of the hands, fingers, elbows, and knees with occasional involvement of the extensor forearms and cheeks. This disorder occurs in predisposed children who have been exposed to significant frictional force during play, and typically resolves spontaneously after removal of the stimulus.

Keratosis pilaris is a rash that usually is found on the outer areas of the upper arms, upper thighs, buttocks, and cheeks. It consists of small bumps that are flesh colored to red. The bumps generally don’t hurt or itch.

The lack of symptoms and spontaneous healing have rendered treatment unnecessary in most cases. LN generally is self-limiting, thus treatment may not be necessary. However, topical treatment with mid- to high-potency corticosteroids has hastened resolution of lesions in some children, as have topical dinitrochlorobenzene and systemic treatment with psoralens, astemizole, etretinate, and psoralen-UVA.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Bhatti is a research fellow in pediatric dermatology at Rady Children’s Hospital and the University of California, San Diego. Neither Dr. Eichenfield nor Dr. Bhatti has any relevant financial disclosures. Email them at pdnews@mdedge.com.

References

Pickert A. Cutis. 2012 Sep;90(3):E1-3. https://mdedge-files-live.s3.us-east-2.amazonaws.com/files/s3fs-public/Document/September-2017/0900300E1.pdf Tziotzios C et al. J Am Acad Dermatol. 2018 Nov;79(5):789-804. Tilly JJ et al. J Am Acad Dermatol. 2004 Oct;51(4):606-24.

ANSWER

The correct answer is to perform a 3-mm punch biopsy (choice “a”).

DISCUSSION

When the history and physical exam fail to point to a clear diagnosis, skin biopsy can answer a very basic question: What is the pathophysiologic process associated with the lesions? The information thus obtained doesn’t always produce a blinking neon sign of a diagnosis, but at a minimum, it can rule out a great number of things, such as cancer or infection.

More often, the types of cells seen, and the patterns in which they are arranged, tell us a great deal. In this case, accumulations of monocytes, macrophages, and activated T-lymphocytes were arranged in circular patterns, but there was no evidence of necrosis (caseation), which can be seen in tubercular granulomas. Stains performed to identify mycobacterial organisms were negative. These findings established the diagnosis of cutaneous sarcoidosis, a granulomatous disease thought to represent a reaction to an unknown antigen (eg, a microorganism) or environmental substance. It is far more common in those with darker skin types.

Although this patient’s disease was confined to the skin, sarcoidosis can affect virtually any other organ in the body—in particular, the lungs, kidneys, liver, nervous system, or even the eyes. For this reason, patients with sarcoidosis are usually referred to pulmonology for a workup intended to rule out systemic involvement and to other specialists as symptoms dictate.

Many cases of sarcoidosis remit on their own, without treatment. When treatment is initiated, the 2 most commonly used medications are systemic glucocorticoids and/or methotrexate. Both drugs have been associated with serious adverse effects and should only be prescribed by experienced providers.

This combination was prescribed for the case patient, who obtained rapid relief. Blood work (complete blood count, comprehensive metabolic panel) was within normal limits prior to and during treatment, and the pulmonologist pronounced her free of lung involvement.

ANSWER

The correct answer is to perform a 3-mm punch biopsy (choice “a”).

DISCUSSION

When the history and physical exam fail to point to a clear diagnosis, skin biopsy can answer a very basic question: What is the pathophysiologic process associated with the lesions? The information thus obtained doesn’t always produce a blinking neon sign of a diagnosis, but at a minimum, it can rule out a great number of things, such as cancer or infection.

More often, the types of cells seen, and the patterns in which they are arranged, tell us a great deal. In this case, accumulations of monocytes, macrophages, and activated T-lymphocytes were arranged in circular patterns, but there was no evidence of necrosis (caseation), which can be seen in tubercular granulomas. Stains performed to identify mycobacterial organisms were negative. These findings established the diagnosis of cutaneous sarcoidosis, a granulomatous disease thought to represent a reaction to an unknown antigen (eg, a microorganism) or environmental substance. It is far more common in those with darker skin types.

Although this patient’s disease was confined to the skin, sarcoidosis can affect virtually any other organ in the body—in particular, the lungs, kidneys, liver, nervous system, or even the eyes. For this reason, patients with sarcoidosis are usually referred to pulmonology for a workup intended to rule out systemic involvement and to other specialists as symptoms dictate.

Many cases of sarcoidosis remit on their own, without treatment. When treatment is initiated, the 2 most commonly used medications are systemic glucocorticoids and/or methotrexate. Both drugs have been associated with serious adverse effects and should only be prescribed by experienced providers.

This combination was prescribed for the case patient, who obtained rapid relief. Blood work (complete blood count, comprehensive metabolic panel) was within normal limits prior to and during treatment, and the pulmonologist pronounced her free of lung involvement.

ANSWER

The correct answer is to perform a 3-mm punch biopsy (choice “a”).

DISCUSSION

When the history and physical exam fail to point to a clear diagnosis, skin biopsy can answer a very basic question: What is the pathophysiologic process associated with the lesions? The information thus obtained doesn’t always produce a blinking neon sign of a diagnosis, but at a minimum, it can rule out a great number of things, such as cancer or infection.

More often, the types of cells seen, and the patterns in which they are arranged, tell us a great deal. In this case, accumulations of monocytes, macrophages, and activated T-lymphocytes were arranged in circular patterns, but there was no evidence of necrosis (caseation), which can be seen in tubercular granulomas. Stains performed to identify mycobacterial organisms were negative. These findings established the diagnosis of cutaneous sarcoidosis, a granulomatous disease thought to represent a reaction to an unknown antigen (eg, a microorganism) or environmental substance. It is far more common in those with darker skin types.

Although this patient’s disease was confined to the skin, sarcoidosis can affect virtually any other organ in the body—in particular, the lungs, kidneys, liver, nervous system, or even the eyes. For this reason, patients with sarcoidosis are usually referred to pulmonology for a workup intended to rule out systemic involvement and to other specialists as symptoms dictate.

Many cases of sarcoidosis remit on their own, without treatment. When treatment is initiated, the 2 most commonly used medications are systemic glucocorticoids and/or methotrexate. Both drugs have been associated with serious adverse effects and should only be prescribed by experienced providers.

This combination was prescribed for the case patient, who obtained rapid relief. Blood work (complete blood count, comprehensive metabolic panel) was within normal limits prior to and during treatment, and the pulmonologist pronounced her free of lung involvement.

PHILADELPHIA – Engaging in at least 150 minutes of moderate to vigorous physical activity per week as recommended in national guidelines appears to mitigate the cardiometabolic risks associated with poor diet quality in middle-aged and older adults, according to an analysis of Framingham Heart Study data.

Bruce Jancin/MDedge News

“Our findings suggest adherence to physical activity guidelines may have a protective effect on cardiometabolic health regardless of diet quality,” Joowon Lee, PhD, declared at the American Heart Association scientific sessions.

He presented separate cross-sectional analyses of the risks of metabolic syndrome in 2,379 middle-aged participants in the National Heart, Lung, and Blood Institute–sponsored Framingham (Mass.) Third Generation Study and 1,180 older participants in the Framingham Offspring Study.

The two analyses showed the same thing across a broad age spectrum: The highest prevalence of metabolic syndrome as defined by Adult Treatment Panel III criteria was present among those individuals who got less than 150 minutes of physical activity per week and were also in the lowest tertile in terms of diet quality, while the lowest prevalence of metabolic syndrome occurred in participants in the top tertile for diet quality who engaged in at least 150 minutes per week of moderate to vigorous physical activity in accord with the Department of Health & Human Services 2018 Physical Activity Guidelines for Americans.

In both the middle-aged and older populations, optimal physical activity – that is, at least 150 minutes per week – appeared to override the adverse impact of suboptimal diet quality. Physically active individuals with moderate or even poor diet quality had a significantly lower prevalence of metabolic syndrome than did the reference group constituted by participants with poor diet quality who didn’t exercise for 150 minutes per week.

But the converse didn’t hold true: Individuals with optimal diet quality who didn’t reach the physical activity threshold had no reduction in metabolic syndrome, compared with the reference group, according to Dr. Lee of Boston University.

For example, among the Framingham Offspring Study participants, whose mean age was 69 years at the time of their ninth formal examination in 2014, the prevalence of metabolic syndrome was 59% in those who got less than 150 minutes of moderate to vigorous physical activity weekly as assessed by accelerometer and who were also in the lowest tertile for diet quality as self-reported on the DGAI-2010 (Dietary Guidelines Adherence Index) semiquantitative food frequency questionnaire. The relative risk of metabolic syndrome was reduced by 61% in participants with both optimal physical activity and diet quality, by 49% in those with at least 150 minutes of physical activity but only moderate diet quality, and by 39% in those with optimal exercise and poor diet quality. In contrast, individuals in the top or middle tertiles for diet quality who didn’t meet the physical activity standard had a metabolic syndrome rate that wasn’t significantly lower than the reference group.

Dr. Lee observed that his analyses are best viewed as hypothesis generating. Their cross-sectional format precludes firm conclusions as to causality.

His findings prompted session comoderator Satyam Sarma, MD, of the University of Texas, Dallas, to make one of the most memorable comments heard at AHA 2019: that the Framingham findings suggest it may be possible to outrun a bad diet.

Dr. Lee reported having no financial conflicts regarding his study, supported by Boston University.

bjancin@mdedge.com

SOURCE: Lee J. AHA 2019, Abstract RF244.

PHILADELPHIA – Engaging in at least 150 minutes of moderate to vigorous physical activity per week as recommended in national guidelines appears to mitigate the cardiometabolic risks associated with poor diet quality in middle-aged and older adults, according to an analysis of Framingham Heart Study data.

Bruce Jancin/MDedge News

“Our findings suggest adherence to physical activity guidelines may have a protective effect on cardiometabolic health regardless of diet quality,” Joowon Lee, PhD, declared at the American Heart Association scientific sessions.

He presented separate cross-sectional analyses of the risks of metabolic syndrome in 2,379 middle-aged participants in the National Heart, Lung, and Blood Institute–sponsored Framingham (Mass.) Third Generation Study and 1,180 older participants in the Framingham Offspring Study.

The two analyses showed the same thing across a broad age spectrum: The highest prevalence of metabolic syndrome as defined by Adult Treatment Panel III criteria was present among those individuals who got less than 150 minutes of physical activity per week and were also in the lowest tertile in terms of diet quality, while the lowest prevalence of metabolic syndrome occurred in participants in the top tertile for diet quality who engaged in at least 150 minutes per week of moderate to vigorous physical activity in accord with the Department of Health & Human Services 2018 Physical Activity Guidelines for Americans.

In both the middle-aged and older populations, optimal physical activity – that is, at least 150 minutes per week – appeared to override the adverse impact of suboptimal diet quality. Physically active individuals with moderate or even poor diet quality had a significantly lower prevalence of metabolic syndrome than did the reference group constituted by participants with poor diet quality who didn’t exercise for 150 minutes per week.

But the converse didn’t hold true: Individuals with optimal diet quality who didn’t reach the physical activity threshold had no reduction in metabolic syndrome, compared with the reference group, according to Dr. Lee of Boston University.

For example, among the Framingham Offspring Study participants, whose mean age was 69 years at the time of their ninth formal examination in 2014, the prevalence of metabolic syndrome was 59% in those who got less than 150 minutes of moderate to vigorous physical activity weekly as assessed by accelerometer and who were also in the lowest tertile for diet quality as self-reported on the DGAI-2010 (Dietary Guidelines Adherence Index) semiquantitative food frequency questionnaire. The relative risk of metabolic syndrome was reduced by 61% in participants with both optimal physical activity and diet quality, by 49% in those with at least 150 minutes of physical activity but only moderate diet quality, and by 39% in those with optimal exercise and poor diet quality. In contrast, individuals in the top or middle tertiles for diet quality who didn’t meet the physical activity standard had a metabolic syndrome rate that wasn’t significantly lower than the reference group.

Dr. Lee observed that his analyses are best viewed as hypothesis generating. Their cross-sectional format precludes firm conclusions as to causality.

His findings prompted session comoderator Satyam Sarma, MD, of the University of Texas, Dallas, to make one of the most memorable comments heard at AHA 2019: that the Framingham findings suggest it may be possible to outrun a bad diet.

Dr. Lee reported having no financial conflicts regarding his study, supported by Boston University.

bjancin@mdedge.com

SOURCE: Lee J. AHA 2019, Abstract RF244.

PHILADELPHIA – Engaging in at least 150 minutes of moderate to vigorous physical activity per week as recommended in national guidelines appears to mitigate the cardiometabolic risks associated with poor diet quality in middle-aged and older adults, according to an analysis of Framingham Heart Study data.

Bruce Jancin/MDedge News

“Our findings suggest adherence to physical activity guidelines may have a protective effect on cardiometabolic health regardless of diet quality,” Joowon Lee, PhD, declared at the American Heart Association scientific sessions.

He presented separate cross-sectional analyses of the risks of metabolic syndrome in 2,379 middle-aged participants in the National Heart, Lung, and Blood Institute–sponsored Framingham (Mass.) Third Generation Study and 1,180 older participants in the Framingham Offspring Study.

The two analyses showed the same thing across a broad age spectrum: The highest prevalence of metabolic syndrome as defined by Adult Treatment Panel III criteria was present among those individuals who got less than 150 minutes of physical activity per week and were also in the lowest tertile in terms of diet quality, while the lowest prevalence of metabolic syndrome occurred in participants in the top tertile for diet quality who engaged in at least 150 minutes per week of moderate to vigorous physical activity in accord with the Department of Health & Human Services 2018 Physical Activity Guidelines for Americans.

In both the middle-aged and older populations, optimal physical activity – that is, at least 150 minutes per week – appeared to override the adverse impact of suboptimal diet quality. Physically active individuals with moderate or even poor diet quality had a significantly lower prevalence of metabolic syndrome than did the reference group constituted by participants with poor diet quality who didn’t exercise for 150 minutes per week.

But the converse didn’t hold true: Individuals with optimal diet quality who didn’t reach the physical activity threshold had no reduction in metabolic syndrome, compared with the reference group, according to Dr. Lee of Boston University.

For example, among the Framingham Offspring Study participants, whose mean age was 69 years at the time of their ninth formal examination in 2014, the prevalence of metabolic syndrome was 59% in those who got less than 150 minutes of moderate to vigorous physical activity weekly as assessed by accelerometer and who were also in the lowest tertile for diet quality as self-reported on the DGAI-2010 (Dietary Guidelines Adherence Index) semiquantitative food frequency questionnaire. The relative risk of metabolic syndrome was reduced by 61% in participants with both optimal physical activity and diet quality, by 49% in those with at least 150 minutes of physical activity but only moderate diet quality, and by 39% in those with optimal exercise and poor diet quality. In contrast, individuals in the top or middle tertiles for diet quality who didn’t meet the physical activity standard had a metabolic syndrome rate that wasn’t significantly lower than the reference group.

Dr. Lee observed that his analyses are best viewed as hypothesis generating. Their cross-sectional format precludes firm conclusions as to causality.

His findings prompted session comoderator Satyam Sarma, MD, of the University of Texas, Dallas, to make one of the most memorable comments heard at AHA 2019: that the Framingham findings suggest it may be possible to outrun a bad diet.

Dr. Lee reported having no financial conflicts regarding his study, supported by Boston University.

bjancin@mdedge.com

SOURCE: Lee J. AHA 2019, Abstract RF244.

Abnormalities in lipids, liver enzymes, and blood counts were rare, and serious abnormalities virtually nonexistent among individuals taking isotretinoin for moderate to severe acne who received laboratory testing.

In a review of 1,863 patients receiving isotretinoin, there were no cases of grade 4 abnormalities of lipids, liver enzymes, or complete blood count (CBC). Further, fewer than 1% of patients had grade 2-3 laboratory abnormalities, and no patients had cholesterol or CBC abnormalities of grade 3 or higher.

The retrospective cohort study used an electronic database to identify patients who were prescribed isotretinoin for acne from 2007 to 2017, with inclusion criteria structured to “increase the likelihood of capturing a complete course of isotretinoin therapy,” wrote John Barbieri, MD, and coauthors. The database allowed the investigators to group lab values into baseline testing, and testing by month of therapy for individual deidentified patient records.

Dr. Barbieri, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, and coinvestigators found that over half of all patients had baseline triglyceride, total cholesterol, AST, ALT, and platelet and white blood cell count levels.

Though the number of patients who had any of these levels checked in a given month of treatment declined over time, as did the total number of patients still on isotretinoin therapy, monthly AST and ALT monitoring occurred in 37.6%-58.5% of patients. Monthly triglyceride monitoring was conducted in between 39.6% and 61.4% of participants, and CBCs were obtained in 26.8%-37.4% of participants.

In terms of the abnormalities that were seen, grade 1 triglyceride elevations of 150-300 mg/dL were present in about 13% of patients at baseline, rising to 39% of participants who were still receiving isotretinoin at month 6. However, grade 2 elevations of up to 500 mg/dL were seen in 1.4% of patients at baseline and 2.4%-5.6% of patients during subsequent months.

Grade 1 liver enzyme abnormalities of less than three times the upper limit of normal values were seen at baseline in under 4% of patients, and in no more than 6.7% of patients through the course of treatment.

Leukopenia of between 3 x 10³/mcL and the lower limit of normal occurred in 4.1% of baseline tests and in 6.6%-10.1% of tests in subsequent months. Grade 1 thrombocytopenia (values between 75 x 10³/mcL and the lower limit of normal) occurred in 1.9% of baseline tests and no more than 2.9% of tests in the following months.

The results, wrote Dr. Barbieri and coauthors, affirm that most patients fare well on isotretinoin, and frequent laboratory testing is likely to be low-yield. Even using relatively low Medicare reimbursement rates for these tests yielded an estimated $134 in per-patient charges for the studied population. If baseline lipid and liver functions were followed only by repeat testing when peak isotretinoin dose was reached, charges would drop to about $87 per patient. Using the iPLEDGE database figures, this would save $17.4 million in monitoring costs annually, they wrote.

They also calculated that the monitoring regimen they observed puts the cost of detecting one single grade 3 hepatic enzyme elevation at $6,000; one grade 3 triglyceride elevation would cost $7,750.

Of the patients, 49% were female, the median age was 18.2 years, and the median duration of isotretinoin therapy was under 5 months (148 days). Nearly 90% of patients were white and non-Hispanic; 2.5% were black.

The data used for the analysis did not give the investigators access to clinician notes, but they did observe that, even when abnormal test values were seen, isotretinoin prescribing continued. This, they added, pointed toward reassuring clinical scenarios, even in cases of abnormal lab values.

“These findings are consistent with prior studies and suggest that extensive laboratory monitoring observed in this population may be of low value,” concluded Dr. Barbieri and colleagues. “In addition, changes to lipid levels observed in this study typically occurred during the first 2-3 months of therapy before stabilizing, which is consistent with findings in prior studies.”

The investigators noted that, despite mounting evidence of isotretinoin’s safety, there was no trend toward decreased CBC testing over the decade-long period of the study, and there were only “modest” decreases in hepatic enzyme and lipid monitoring. They called for an awareness campaign on the part of professional societies, and consideration for “more specific guideline recommendations” that may ease the testing burden on the adolescent and young adult population receiving isotretinoin.

The study was funded in part by the National Institutes of Health, and Dr. Barbieri receives partial salary support from Pfizer through a grant to the University of Pennsylvania. He has received support for unrelated work from Eli Lilly and Novartis. The other authors reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Barbieri J et al. J Am Acad Dermatol. 2020 Jan;82(1):72-9.

Abnormalities in lipids, liver enzymes, and blood counts were rare, and serious abnormalities virtually nonexistent among individuals taking isotretinoin for moderate to severe acne who received laboratory testing.

In a review of 1,863 patients receiving isotretinoin, there were no cases of grade 4 abnormalities of lipids, liver enzymes, or complete blood count (CBC). Further, fewer than 1% of patients had grade 2-3 laboratory abnormalities, and no patients had cholesterol or CBC abnormalities of grade 3 or higher.

The retrospective cohort study used an electronic database to identify patients who were prescribed isotretinoin for acne from 2007 to 2017, with inclusion criteria structured to “increase the likelihood of capturing a complete course of isotretinoin therapy,” wrote John Barbieri, MD, and coauthors. The database allowed the investigators to group lab values into baseline testing, and testing by month of therapy for individual deidentified patient records.

Dr. Barbieri, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, and coinvestigators found that over half of all patients had baseline triglyceride, total cholesterol, AST, ALT, and platelet and white blood cell count levels.

Though the number of patients who had any of these levels checked in a given month of treatment declined over time, as did the total number of patients still on isotretinoin therapy, monthly AST and ALT monitoring occurred in 37.6%-58.5% of patients. Monthly triglyceride monitoring was conducted in between 39.6% and 61.4% of participants, and CBCs were obtained in 26.8%-37.4% of participants.

In terms of the abnormalities that were seen, grade 1 triglyceride elevations of 150-300 mg/dL were present in about 13% of patients at baseline, rising to 39% of participants who were still receiving isotretinoin at month 6. However, grade 2 elevations of up to 500 mg/dL were seen in 1.4% of patients at baseline and 2.4%-5.6% of patients during subsequent months.

Grade 1 liver enzyme abnormalities of less than three times the upper limit of normal values were seen at baseline in under 4% of patients, and in no more than 6.7% of patients through the course of treatment.

Leukopenia of between 3 x 10³/mcL and the lower limit of normal occurred in 4.1% of baseline tests and in 6.6%-10.1% of tests in subsequent months. Grade 1 thrombocytopenia (values between 75 x 10³/mcL and the lower limit of normal) occurred in 1.9% of baseline tests and no more than 2.9% of tests in the following months.

The results, wrote Dr. Barbieri and coauthors, affirm that most patients fare well on isotretinoin, and frequent laboratory testing is likely to be low-yield. Even using relatively low Medicare reimbursement rates for these tests yielded an estimated $134 in per-patient charges for the studied population. If baseline lipid and liver functions were followed only by repeat testing when peak isotretinoin dose was reached, charges would drop to about $87 per patient. Using the iPLEDGE database figures, this would save $17.4 million in monitoring costs annually, they wrote.

They also calculated that the monitoring regimen they observed puts the cost of detecting one single grade 3 hepatic enzyme elevation at $6,000; one grade 3 triglyceride elevation would cost $7,750.

Of the patients, 49% were female, the median age was 18.2 years, and the median duration of isotretinoin therapy was under 5 months (148 days). Nearly 90% of patients were white and non-Hispanic; 2.5% were black.

The data used for the analysis did not give the investigators access to clinician notes, but they did observe that, even when abnormal test values were seen, isotretinoin prescribing continued. This, they added, pointed toward reassuring clinical scenarios, even in cases of abnormal lab values.

“These findings are consistent with prior studies and suggest that extensive laboratory monitoring observed in this population may be of low value,” concluded Dr. Barbieri and colleagues. “In addition, changes to lipid levels observed in this study typically occurred during the first 2-3 months of therapy before stabilizing, which is consistent with findings in prior studies.”

The investigators noted that, despite mounting evidence of isotretinoin’s safety, there was no trend toward decreased CBC testing over the decade-long period of the study, and there were only “modest” decreases in hepatic enzyme and lipid monitoring. They called for an awareness campaign on the part of professional societies, and consideration for “more specific guideline recommendations” that may ease the testing burden on the adolescent and young adult population receiving isotretinoin.

The study was funded in part by the National Institutes of Health, and Dr. Barbieri receives partial salary support from Pfizer through a grant to the University of Pennsylvania. He has received support for unrelated work from Eli Lilly and Novartis. The other authors reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Barbieri J et al. J Am Acad Dermatol. 2020 Jan;82(1):72-9.

Abnormalities in lipids, liver enzymes, and blood counts were rare, and serious abnormalities virtually nonexistent among individuals taking isotretinoin for moderate to severe acne who received laboratory testing.

In a review of 1,863 patients receiving isotretinoin, there were no cases of grade 4 abnormalities of lipids, liver enzymes, or complete blood count (CBC). Further, fewer than 1% of patients had grade 2-3 laboratory abnormalities, and no patients had cholesterol or CBC abnormalities of grade 3 or higher.

The retrospective cohort study used an electronic database to identify patients who were prescribed isotretinoin for acne from 2007 to 2017, with inclusion criteria structured to “increase the likelihood of capturing a complete course of isotretinoin therapy,” wrote John Barbieri, MD, and coauthors. The database allowed the investigators to group lab values into baseline testing, and testing by month of therapy for individual deidentified patient records.

Dr. Barbieri, a dermatologist and postdoctoral research fellow at the University of Pennsylvania, Philadelphia, and coinvestigators found that over half of all patients had baseline triglyceride, total cholesterol, AST, ALT, and platelet and white blood cell count levels.

Though the number of patients who had any of these levels checked in a given month of treatment declined over time, as did the total number of patients still on isotretinoin therapy, monthly AST and ALT monitoring occurred in 37.6%-58.5% of patients. Monthly triglyceride monitoring was conducted in between 39.6% and 61.4% of participants, and CBCs were obtained in 26.8%-37.4% of participants.

In terms of the abnormalities that were seen, grade 1 triglyceride elevations of 150-300 mg/dL were present in about 13% of patients at baseline, rising to 39% of participants who were still receiving isotretinoin at month 6. However, grade 2 elevations of up to 500 mg/dL were seen in 1.4% of patients at baseline and 2.4%-5.6% of patients during subsequent months.

Grade 1 liver enzyme abnormalities of less than three times the upper limit of normal values were seen at baseline in under 4% of patients, and in no more than 6.7% of patients through the course of treatment.

Leukopenia of between 3 x 10³/mcL and the lower limit of normal occurred in 4.1% of baseline tests and in 6.6%-10.1% of tests in subsequent months. Grade 1 thrombocytopenia (values between 75 x 10³/mcL and the lower limit of normal) occurred in 1.9% of baseline tests and no more than 2.9% of tests in the following months.

The results, wrote Dr. Barbieri and coauthors, affirm that most patients fare well on isotretinoin, and frequent laboratory testing is likely to be low-yield. Even using relatively low Medicare reimbursement rates for these tests yielded an estimated $134 in per-patient charges for the studied population. If baseline lipid and liver functions were followed only by repeat testing when peak isotretinoin dose was reached, charges would drop to about $87 per patient. Using the iPLEDGE database figures, this would save $17.4 million in monitoring costs annually, they wrote.

They also calculated that the monitoring regimen they observed puts the cost of detecting one single grade 3 hepatic enzyme elevation at $6,000; one grade 3 triglyceride elevation would cost $7,750.

Of the patients, 49% were female, the median age was 18.2 years, and the median duration of isotretinoin therapy was under 5 months (148 days). Nearly 90% of patients were white and non-Hispanic; 2.5% were black.

The data used for the analysis did not give the investigators access to clinician notes, but they did observe that, even when abnormal test values were seen, isotretinoin prescribing continued. This, they added, pointed toward reassuring clinical scenarios, even in cases of abnormal lab values.

“These findings are consistent with prior studies and suggest that extensive laboratory monitoring observed in this population may be of low value,” concluded Dr. Barbieri and colleagues. “In addition, changes to lipid levels observed in this study typically occurred during the first 2-3 months of therapy before stabilizing, which is consistent with findings in prior studies.”

The investigators noted that, despite mounting evidence of isotretinoin’s safety, there was no trend toward decreased CBC testing over the decade-long period of the study, and there were only “modest” decreases in hepatic enzyme and lipid monitoring. They called for an awareness campaign on the part of professional societies, and consideration for “more specific guideline recommendations” that may ease the testing burden on the adolescent and young adult population receiving isotretinoin.

The study was funded in part by the National Institutes of Health, and Dr. Barbieri receives partial salary support from Pfizer through a grant to the University of Pennsylvania. He has received support for unrelated work from Eli Lilly and Novartis. The other authors reported no conflicts of interest.

koakes@mdedge.com

SOURCE: Barbieri J et al. J Am Acad Dermatol. 2020 Jan;82(1):72-9.

Gastroenterology

November 2019

Clip closure after resection of large colorectal lesions with substantial risk of bleeding. Albéniz E et al. 2019 Nov;157(5):1213-21.e4. doi. 10.1053/j.gastro.2019.07.037.

Tumor seeding during colonoscopy as a possible cause for metachronous colorectal cancer. Backes Y et al. 2019 Nov;157(5):1222-32.e4. doi. 10.1053/j.gastro.2019.07.062.

December 2019

How to “DEAL” with disruptive physician behavior. Junga Z et al. 2019 Dec;157(6):1469-72. doi. 10.1053/j.gastro.2019.10.021.

Effect of sex, age, and positivity threshold on fecal immunochemical test accuracy: A systematic review and meta-analysis. Selby K et al. 2019 Dec;(6):1494-505. doi. 10.1053/j.gastro.2019.08.023.

January 2020

How to approach burnout among gastroenterology fellows. DeCross AJ 2020 Jan;158(1):32-5. doi. 10.1053/j.gastro.2019.11.032.

Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Weerts ZZRM et al. 2020 Jan;158(1):123-36. doi. 10.1053/j.gastro.2019.08.026.

Validation of a machine learning model that outperforms clinical risk scoring systems for upper gastrointestinal bleeding. Shung DL et al. 2020 Jan;158(1):160-7. doi. 10.1053/j.gastro.2019.09.009.

Efficacy and safety of early vs elective colonoscopy for acute lower gastrointestinal bleeding. Niikura R et al. 2020 Jan;158(1):168-75.e6. doi. 10.1053/j.gastro.2019.09.010.

Clinical Gastroenterology and Hepatology

November 2019

Medical professional liability in gastroenterology: Understanding the claims landscape and proposed mechanisms for reform. Adams MA and John I. Allen. 2019 Nov;17(12):2392-6.e1. doi. 10.1016/j.cgh.2019.07.002.

Optimizing use of nonalcoholic fatty liver disease fibrosis score, Fibrosis-4 score, and liver stiffness measurement to identify patients with advanced fibrosis. Chan W-K et al. 2019 Nov;17(12):2570-80.e37. doi. 10.1016/j.cgh.2019.03.006.

December 2019

Clinical and molecular features of post-colonoscopy colorectal cancers. Samadder NJ et al. 2019 Dec;17(12):2731-9.e2. doi. 10.1016/j.cgh.2019.02.040.

Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to transglutaminase 6. Hadjivassiliou M et al. 2019 Dec;17(12):2678-86.e2. doi. 10.1016/j.cgh.2019.03.014.

Increased risk of death in first year after liver transplantation among patients with nonalcoholic steatohepatitis vs liver disease of other etiologies. Nagai S et al. 2019 Dec;17(12):2759-68.e5. doi. 10.1016/j.cgh.2019.04.033.

January 2020

Incorporating high value care into gastroenterology fellowship training. Shah BJ and Janice H. Jou. 2020 Jan;18(1):11-3. doi. 10.1016/j.cgh.2019.10.040.

Association of obesity with colonic diverticulosis in women. Peery AF et al. 2020 Jan;18(1):107-14.e1. doi. 10.1016/j.cgh.2019.04.058.

Endocuff vision reduces inspection time without decreasing lesion detection: A clinical randomized trial. Rex DK et al. 2020 Jan;18(1):158-62.e1 doi. 10.1016/j.cgh.2019.01.015.

Gastroenterology

November 2019

Clip closure after resection of large colorectal lesions with substantial risk of bleeding. Albéniz E et al. 2019 Nov;157(5):1213-21.e4. doi. 10.1053/j.gastro.2019.07.037.

Tumor seeding during colonoscopy as a possible cause for metachronous colorectal cancer. Backes Y et al. 2019 Nov;157(5):1222-32.e4. doi. 10.1053/j.gastro.2019.07.062.

December 2019

How to “DEAL” with disruptive physician behavior. Junga Z et al. 2019 Dec;157(6):1469-72. doi. 10.1053/j.gastro.2019.10.021.

Effect of sex, age, and positivity threshold on fecal immunochemical test accuracy: A systematic review and meta-analysis. Selby K et al. 2019 Dec;(6):1494-505. doi. 10.1053/j.gastro.2019.08.023.

January 2020

How to approach burnout among gastroenterology fellows. DeCross AJ 2020 Jan;158(1):32-5. doi. 10.1053/j.gastro.2019.11.032.

Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Weerts ZZRM et al. 2020 Jan;158(1):123-36. doi. 10.1053/j.gastro.2019.08.026.

Validation of a machine learning model that outperforms clinical risk scoring systems for upper gastrointestinal bleeding. Shung DL et al. 2020 Jan;158(1):160-7. doi. 10.1053/j.gastro.2019.09.009.

Efficacy and safety of early vs elective colonoscopy for acute lower gastrointestinal bleeding. Niikura R et al. 2020 Jan;158(1):168-75.e6. doi. 10.1053/j.gastro.2019.09.010.

Clinical Gastroenterology and Hepatology

November 2019

Medical professional liability in gastroenterology: Understanding the claims landscape and proposed mechanisms for reform. Adams MA and John I. Allen. 2019 Nov;17(12):2392-6.e1. doi. 10.1016/j.cgh.2019.07.002.

Optimizing use of nonalcoholic fatty liver disease fibrosis score, Fibrosis-4 score, and liver stiffness measurement to identify patients with advanced fibrosis. Chan W-K et al. 2019 Nov;17(12):2570-80.e37. doi. 10.1016/j.cgh.2019.03.006.

December 2019

Clinical and molecular features of post-colonoscopy colorectal cancers. Samadder NJ et al. 2019 Dec;17(12):2731-9.e2. doi. 10.1016/j.cgh.2019.02.040.

Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to transglutaminase 6. Hadjivassiliou M et al. 2019 Dec;17(12):2678-86.e2. doi. 10.1016/j.cgh.2019.03.014.

Increased risk of death in first year after liver transplantation among patients with nonalcoholic steatohepatitis vs liver disease of other etiologies. Nagai S et al. 2019 Dec;17(12):2759-68.e5. doi. 10.1016/j.cgh.2019.04.033.

January 2020

Incorporating high value care into gastroenterology fellowship training. Shah BJ and Janice H. Jou. 2020 Jan;18(1):11-3. doi. 10.1016/j.cgh.2019.10.040.

Association of obesity with colonic diverticulosis in women. Peery AF et al. 2020 Jan;18(1):107-14.e1. doi. 10.1016/j.cgh.2019.04.058.

Endocuff vision reduces inspection time without decreasing lesion detection: A clinical randomized trial. Rex DK et al. 2020 Jan;18(1):158-62.e1 doi. 10.1016/j.cgh.2019.01.015.

Gastroenterology

November 2019

Clip closure after resection of large colorectal lesions with substantial risk of bleeding. Albéniz E et al. 2019 Nov;157(5):1213-21.e4. doi. 10.1053/j.gastro.2019.07.037.

Tumor seeding during colonoscopy as a possible cause for metachronous colorectal cancer. Backes Y et al. 2019 Nov;157(5):1222-32.e4. doi. 10.1053/j.gastro.2019.07.062.

December 2019

How to “DEAL” with disruptive physician behavior. Junga Z et al. 2019 Dec;157(6):1469-72. doi. 10.1053/j.gastro.2019.10.021.

Effect of sex, age, and positivity threshold on fecal immunochemical test accuracy: A systematic review and meta-analysis. Selby K et al. 2019 Dec;(6):1494-505. doi. 10.1053/j.gastro.2019.08.023.

January 2020

How to approach burnout among gastroenterology fellows. DeCross AJ 2020 Jan;158(1):32-5. doi. 10.1053/j.gastro.2019.11.032.

Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Weerts ZZRM et al. 2020 Jan;158(1):123-36. doi. 10.1053/j.gastro.2019.08.026.

Validation of a machine learning model that outperforms clinical risk scoring systems for upper gastrointestinal bleeding. Shung DL et al. 2020 Jan;158(1):160-7. doi. 10.1053/j.gastro.2019.09.009.

Efficacy and safety of early vs elective colonoscopy for acute lower gastrointestinal bleeding. Niikura R et al. 2020 Jan;158(1):168-75.e6. doi. 10.1053/j.gastro.2019.09.010.

Clinical Gastroenterology and Hepatology

November 2019

Medical professional liability in gastroenterology: Understanding the claims landscape and proposed mechanisms for reform. Adams MA and John I. Allen. 2019 Nov;17(12):2392-6.e1. doi. 10.1016/j.cgh.2019.07.002.

Optimizing use of nonalcoholic fatty liver disease fibrosis score, Fibrosis-4 score, and liver stiffness measurement to identify patients with advanced fibrosis. Chan W-K et al. 2019 Nov;17(12):2570-80.e37. doi. 10.1016/j.cgh.2019.03.006.

December 2019

Clinical and molecular features of post-colonoscopy colorectal cancers. Samadder NJ et al. 2019 Dec;17(12):2731-9.e2. doi. 10.1016/j.cgh.2019.02.040.

Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to transglutaminase 6. Hadjivassiliou M et al. 2019 Dec;17(12):2678-86.e2. doi. 10.1016/j.cgh.2019.03.014.

Increased risk of death in first year after liver transplantation among patients with nonalcoholic steatohepatitis vs liver disease of other etiologies. Nagai S et al. 2019 Dec;17(12):2759-68.e5. doi. 10.1016/j.cgh.2019.04.033.

January 2020

Incorporating high value care into gastroenterology fellowship training. Shah BJ and Janice H. Jou. 2020 Jan;18(1):11-3. doi. 10.1016/j.cgh.2019.10.040.

Association of obesity with colonic diverticulosis in women. Peery AF et al. 2020 Jan;18(1):107-14.e1. doi. 10.1016/j.cgh.2019.04.058.

Endocuff vision reduces inspection time without decreasing lesion detection: A clinical randomized trial. Rex DK et al. 2020 Jan;18(1):158-62.e1 doi. 10.1016/j.cgh.2019.01.015.

The rash was consistent with nonblanching purpura. Two punch biopsies were performed for hematoxylin and eosin stain and direct immunofluorescence, which were consistent with IgA mediated small vessel vasculitis, or Henoch-Schoenlein purpura.

IgA small vessel vasculitis commonly occurs in children after a transient viral illness or as an allergic reaction to a medication. Nonblanching purpura occurs because small vessels have been cracked open by neutrophils and lymphocytes and leaked blood cells outside of the vascular circulation. Pressure fails to move these cells downstream, and thus, the skin does not blanch.

Joint pain is common, as is a self-resolving IgA mediated nephropathy. Approximately 1% to 3% of children will progress to end stage renal disease. IgA vasculitis also occurs in adults, with a higher portion developing nephropathy. In adults, lesions that present on the abdomen are suspected to correspond with gravity dependency and the total burden of IgA, leading to a higher risk for nephropathy.

The differential diagnosis of purpura is broad, but includes leukocytoclastic vasculitis, antineutrophil cytoplasmic antibodies-associated vasculitis, capillaritis, and disseminated intravascular coagulation.

The patient in this case was given topical triamcinolone 0.1% ointment to treat the rash. She returned 3 weeks later and her blood pressure was 160/105 mm Hg and she had protein and blood in her urine. The FP recommended a renal biopsy, which confirmed severe IgA nephropathy and end stage renal failure. She was given systemic steroids and ultimately received a renal transplant. Her outcome was atypical and unfortunate. Usually IgA vasculitis is benign and self-resolves with rest. Even when nephropathy is present, it typically resolves over weeks to months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The rash was consistent with nonblanching purpura. Two punch biopsies were performed for hematoxylin and eosin stain and direct immunofluorescence, which were consistent with IgA mediated small vessel vasculitis, or Henoch-Schoenlein purpura.

IgA small vessel vasculitis commonly occurs in children after a transient viral illness or as an allergic reaction to a medication. Nonblanching purpura occurs because small vessels have been cracked open by neutrophils and lymphocytes and leaked blood cells outside of the vascular circulation. Pressure fails to move these cells downstream, and thus, the skin does not blanch.

Joint pain is common, as is a self-resolving IgA mediated nephropathy. Approximately 1% to 3% of children will progress to end stage renal disease. IgA vasculitis also occurs in adults, with a higher portion developing nephropathy. In adults, lesions that present on the abdomen are suspected to correspond with gravity dependency and the total burden of IgA, leading to a higher risk for nephropathy.

The differential diagnosis of purpura is broad, but includes leukocytoclastic vasculitis, antineutrophil cytoplasmic antibodies-associated vasculitis, capillaritis, and disseminated intravascular coagulation.

The patient in this case was given topical triamcinolone 0.1% ointment to treat the rash. She returned 3 weeks later and her blood pressure was 160/105 mm Hg and she had protein and blood in her urine. The FP recommended a renal biopsy, which confirmed severe IgA nephropathy and end stage renal failure. She was given systemic steroids and ultimately received a renal transplant. Her outcome was atypical and unfortunate. Usually IgA vasculitis is benign and self-resolves with rest. Even when nephropathy is present, it typically resolves over weeks to months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The rash was consistent with nonblanching purpura. Two punch biopsies were performed for hematoxylin and eosin stain and direct immunofluorescence, which were consistent with IgA mediated small vessel vasculitis, or Henoch-Schoenlein purpura.

IgA small vessel vasculitis commonly occurs in children after a transient viral illness or as an allergic reaction to a medication. Nonblanching purpura occurs because small vessels have been cracked open by neutrophils and lymphocytes and leaked blood cells outside of the vascular circulation. Pressure fails to move these cells downstream, and thus, the skin does not blanch.

Joint pain is common, as is a self-resolving IgA mediated nephropathy. Approximately 1% to 3% of children will progress to end stage renal disease. IgA vasculitis also occurs in adults, with a higher portion developing nephropathy. In adults, lesions that present on the abdomen are suspected to correspond with gravity dependency and the total burden of IgA, leading to a higher risk for nephropathy.

The differential diagnosis of purpura is broad, but includes leukocytoclastic vasculitis, antineutrophil cytoplasmic antibodies-associated vasculitis, capillaritis, and disseminated intravascular coagulation.

The patient in this case was given topical triamcinolone 0.1% ointment to treat the rash. She returned 3 weeks later and her blood pressure was 160/105 mm Hg and she had protein and blood in her urine. The FP recommended a renal biopsy, which confirmed severe IgA nephropathy and end stage renal failure. She was given systemic steroids and ultimately received a renal transplant. Her outcome was atypical and unfortunate. Usually IgA vasculitis is benign and self-resolves with rest. Even when nephropathy is present, it typically resolves over weeks to months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Tart cherry concentrate had no impact on gout flares over a 28-day period, based on data from 50 adult patients.

lisaaMC/iStock/Getty Images Plus

Urate-lowering therapy is part of gout management, and previous studies have suggested that tart cherry concentrate lowers sodium urate within hours in healthy volunteers and to a nonsignificant extent over 120 days in patients with gout, but “the optimal dose of tart cherry concentrate for either a serum urate effect on or flare prevention is unknown,” wrote Lisa K. Stamp, MD, of the University of Otago, Christchurch, New Zealand, and colleagues.

In a study published in Rheumatology, the researchers randomized 50 adults with gout and baseline serum urate levels greater than 0.36 mmol/L (6 mg/dL) to receive one of four doses of tart cherry juice concentrate (7.5 mL, 15 mL, 22.5 mL, or 30 mL) or a placebo twice daily for 28 days. Half of the participants were taking allopurinol and half were not taking any urate-lowering therapy.

After 28 days, patients who received cherry juice showed no significant changes in serum urate regardless of whether they were also taking allopurinol. In addition, cherry juice at any dose had no significant effect on reducing the serum urate area under the curve and no apparent impact on measures including urine urate excretion, change in urinary anthocyanins, and frequency of gout flares, compared with placebo. However, the cherry juice was well tolerated, and 84% of the study participants said they would recommend it to a friend as a method of gout prevention.

The researchers collected blood samples at baseline, and at 1, 3, and 5 hours after consuming cherry juice, and on days 1, 3, 7, 14, 21, and 28. “If there is an effect of cherry concentrate on gout flares over a longer time period, it is not likely to be mediated by reduction in serum urate,” the researchers said.

Of 24 adverse events reported during the study, 18 occurred in patients taking cherry juice at all dosage levels, and one case of hyperglycemia was potentially related to cherry concentrate. No serious adverse events associated with tart cherry concentrate occurred during the study period.

The study findings were limited by several factors including the inability to blind the study because participants prepared their doses at home, and the lack of data on the exact contents of the cherry juice concentrate used in the study, the researchers noted. However, the results suggest that tart cherry concentrate has no effect on serum urate concentration or urinary urate excretion, which make it unlikely to be useful in reducing gout flares, they concluded.

The study was supported by the Health Research Council of New Zealand. The researchers had no financial conflicts to disclose.

SOURCE: Stamp LK et al. Rheumatology. 2019 Dec 31. doi: 10.1093/rheumatology/kez606.

Tart cherry concentrate had no impact on gout flares over a 28-day period, based on data from 50 adult patients.

lisaaMC/iStock/Getty Images Plus

Urate-lowering therapy is part of gout management, and previous studies have suggested that tart cherry concentrate lowers sodium urate within hours in healthy volunteers and to a nonsignificant extent over 120 days in patients with gout, but “the optimal dose of tart cherry concentrate for either a serum urate effect on or flare prevention is unknown,” wrote Lisa K. Stamp, MD, of the University of Otago, Christchurch, New Zealand, and colleagues.

In a study published in Rheumatology, the researchers randomized 50 adults with gout and baseline serum urate levels greater than 0.36 mmol/L (6 mg/dL) to receive one of four doses of tart cherry juice concentrate (7.5 mL, 15 mL, 22.5 mL, or 30 mL) or a placebo twice daily for 28 days. Half of the participants were taking allopurinol and half were not taking any urate-lowering therapy.

After 28 days, patients who received cherry juice showed no significant changes in serum urate regardless of whether they were also taking allopurinol. In addition, cherry juice at any dose had no significant effect on reducing the serum urate area under the curve and no apparent impact on measures including urine urate excretion, change in urinary anthocyanins, and frequency of gout flares, compared with placebo. However, the cherry juice was well tolerated, and 84% of the study participants said they would recommend it to a friend as a method of gout prevention.

The researchers collected blood samples at baseline, and at 1, 3, and 5 hours after consuming cherry juice, and on days 1, 3, 7, 14, 21, and 28. “If there is an effect of cherry concentrate on gout flares over a longer time period, it is not likely to be mediated by reduction in serum urate,” the researchers said.

Of 24 adverse events reported during the study, 18 occurred in patients taking cherry juice at all dosage levels, and one case of hyperglycemia was potentially related to cherry concentrate. No serious adverse events associated with tart cherry concentrate occurred during the study period.

The study findings were limited by several factors including the inability to blind the study because participants prepared their doses at home, and the lack of data on the exact contents of the cherry juice concentrate used in the study, the researchers noted. However, the results suggest that tart cherry concentrate has no effect on serum urate concentration or urinary urate excretion, which make it unlikely to be useful in reducing gout flares, they concluded.

The study was supported by the Health Research Council of New Zealand. The researchers had no financial conflicts to disclose.

SOURCE: Stamp LK et al. Rheumatology. 2019 Dec 31. doi: 10.1093/rheumatology/kez606.

Tart cherry concentrate had no impact on gout flares over a 28-day period, based on data from 50 adult patients.

lisaaMC/iStock/Getty Images Plus

Urate-lowering therapy is part of gout management, and previous studies have suggested that tart cherry concentrate lowers sodium urate within hours in healthy volunteers and to a nonsignificant extent over 120 days in patients with gout, but “the optimal dose of tart cherry concentrate for either a serum urate effect on or flare prevention is unknown,” wrote Lisa K. Stamp, MD, of the University of Otago, Christchurch, New Zealand, and colleagues.

In a study published in Rheumatology, the researchers randomized 50 adults with gout and baseline serum urate levels greater than 0.36 mmol/L (6 mg/dL) to receive one of four doses of tart cherry juice concentrate (7.5 mL, 15 mL, 22.5 mL, or 30 mL) or a placebo twice daily for 28 days. Half of the participants were taking allopurinol and half were not taking any urate-lowering therapy.

After 28 days, patients who received cherry juice showed no significant changes in serum urate regardless of whether they were also taking allopurinol. In addition, cherry juice at any dose had no significant effect on reducing the serum urate area under the curve and no apparent impact on measures including urine urate excretion, change in urinary anthocyanins, and frequency of gout flares, compared with placebo. However, the cherry juice was well tolerated, and 84% of the study participants said they would recommend it to a friend as a method of gout prevention.

The researchers collected blood samples at baseline, and at 1, 3, and 5 hours after consuming cherry juice, and on days 1, 3, 7, 14, 21, and 28. “If there is an effect of cherry concentrate on gout flares over a longer time period, it is not likely to be mediated by reduction in serum urate,” the researchers said.

Of 24 adverse events reported during the study, 18 occurred in patients taking cherry juice at all dosage levels, and one case of hyperglycemia was potentially related to cherry concentrate. No serious adverse events associated with tart cherry concentrate occurred during the study period.

The study findings were limited by several factors including the inability to blind the study because participants prepared their doses at home, and the lack of data on the exact contents of the cherry juice concentrate used in the study, the researchers noted. However, the results suggest that tart cherry concentrate has no effect on serum urate concentration or urinary urate excretion, which make it unlikely to be useful in reducing gout flares, they concluded.

The study was supported by the Health Research Council of New Zealand. The researchers had no financial conflicts to disclose.

SOURCE: Stamp LK et al. Rheumatology. 2019 Dec 31. doi: 10.1093/rheumatology/kez606.

ORLANDO – Adding rituximab to standard induction chemotherapy in adults with precursor B-cell acute lymphoblastic leukemia (B-ALL) appears to improve event-free survival, but four doses are insufficient, according to the first analysis from the randomized, phase 3 UKALL14 trial.

VashiDonsk/Creative Commons/CC ASA 3.0

The findings also suggest that the significant event-free survival (EFS) benefit of adding 16-18 doses of rituximab in B-ALL patients, as demonstrated in “the recent and very important” GRAALL-2005/R study, may be generalizable to B-precursor ALL patients regardless of Philadelphia (Ph) chromosome status or CD20-positive expression level, Adele K. Fielding, MBBS, PhD, reported at the annual meeting of the American Society of Hematology.

Unlike GRAALL-2005/R (NCT00327678), which included only patients with greater than 20% of ALL blasts expressing CD20 and with Ph-negative ALL, UKALL14 (NCT01085617) included B-ALL patients regardless of Ph chromosome status or CD20 expression level, explained Dr. Fielding of the Cancer Institute, University College London.

Overall, EFS rates among patients in the UKALL14 study at a median follow-up of 40.5 months were 41.9% in 288 patients randomized to receive standard-of-care chemotherapy (SOC), and 48.7% among 289 randomized to receive SOC plus rituximab, but the difference was not statistically significant (hazard ratio, 0.88; P = .28), she said.

“Likewise there was a nonsignificant improvement in 3-year event-free survival and in median event-free survival in the rituximab arms, but these differences did not meet our predetermined criteria,” she added.

Similarly, the overall survival findings showed slight, but non–statistically significant improvement in the rituximab arms (HR, 0.9; P = .39). The 3-year and median overall survival outcomes appeared to favor rituximab, but “this was not the magnitude of benefit that we were seeking in our study,” she said.

However, while a preplanned subgroup analysis by cytogenetic and other risk groups, as well as by cell surface CD20 expression, did not reveal any significant interactions for EFS, they did show that the percentage of blasts expressing CD20 was a strong independent poor prognostic factor.

A cutoff of 11.6%, compared with the 20% typically used, was found to be ideal based on the Youden Index, which determines the best balance between sensitivity and specificity.

“Interestingly, in addition to this, we did not find any impact of CD20 expression on response to rituximab,” Dr. Fielding noted.

Further, outcomes analyses by post–induction treatment assignment showed that, in patients who received myeloablative allogeneic stem cell transplant, “there was a large and statistically significant benefit to [adding rituximab], she said.

Landmark analysis showed an EFS hazard ratio of 0.48 at the time of transplant (P = .037), she said, noting that the SOC and SOC plus rituximab arms were well matched among this subset of patients.

The difference appeared to relate to relapse risk (HR, .38), but on an intention-to-treat analysis including all patients under age 40 years, the difference was “no longer quite so pronounced.”

“We do not understand the biological basis for this finding,” Dr. Fielding said, noting that it wasn’t explained by differences in graft-versus-host disease or infection. “This difference was not apparent in patients who received or were intended to receive reduced-intensity allogeneic conditioning.”

A multivariable analysis did not show a significant treatment effect, but did show “the same trend toward a better outcome in the rituximab arm,” she added.

UKALL14 subjects were adults aged 25-65 years with de novo ALL, regardless of Ph status or cell surface CD20 expression, who were recruited from 70 centers in the United Kingdom between December 2010 and July 2017. Those randomized to standard of care received a standard four-drug induction after a steroid prephase – with or without four doses of rituximab.

After a second induction, patients underwent risk assessment; low-risk patients were treated on the SOC arm and received high-dose methotrexate and additional pegylated asparaginase followed by four cycles of consolidation therapy. This was followed by 2 years of maintenance treatment.

High-risk patients with a sibling or fully matched unrelated donor available underwent allogeneic stem cell transplant, with those aged 40 years and younger receiving myeloablative conditioning and those over 40 years receiving reduced-intensity conditioning.

Most patients in the SOC plus rituximab arm received all four doses of rituximab, and the treatment arms were well-balanced with respect to risk characteristics, Dr. Fielding said, adding that no differences were noted in adverse events or mortality between the arms.

There is strong rationale for studying rituximab in ALL, she noted. For example, rituximab is safe to add to chemotherapy, and it has potential relevance at any level of CD20 expression, she said, explaining the basis for the study. Indeed, the findings support its use in this setting.

“Rituximab benefits patients with ALL,” she said. “But in our hands, four doses is insufficient to realize the full benefit.”

Dr. Fielding is a consultant for Amgen, Novartis, Pfizer, and Incyte.

sworcester@mdedge.com

SOURCE: Marks D et al. ASH 2019, Abstract 739.

ORLANDO – Adding rituximab to standard induction chemotherapy in adults with precursor B-cell acute lymphoblastic leukemia (B-ALL) appears to improve event-free survival, but four doses are insufficient, according to the first analysis from the randomized, phase 3 UKALL14 trial.

VashiDonsk/Creative Commons/CC ASA 3.0

The findings also suggest that the significant event-free survival (EFS) benefit of adding 16-18 doses of rituximab in B-ALL patients, as demonstrated in “the recent and very important” GRAALL-2005/R study, may be generalizable to B-precursor ALL patients regardless of Philadelphia (Ph) chromosome status or CD20-positive expression level, Adele K. Fielding, MBBS, PhD, reported at the annual meeting of the American Society of Hematology.

Unlike GRAALL-2005/R (NCT00327678), which included only patients with greater than 20% of ALL blasts expressing CD20 and with Ph-negative ALL, UKALL14 (NCT01085617) included B-ALL patients regardless of Ph chromosome status or CD20 expression level, explained Dr. Fielding of the Cancer Institute, University College London.

Overall, EFS rates among patients in the UKALL14 study at a median follow-up of 40.5 months were 41.9% in 288 patients randomized to receive standard-of-care chemotherapy (SOC), and 48.7% among 289 randomized to receive SOC plus rituximab, but the difference was not statistically significant (hazard ratio, 0.88; P = .28), she said.

“Likewise there was a nonsignificant improvement in 3-year event-free survival and in median event-free survival in the rituximab arms, but these differences did not meet our predetermined criteria,” she added.

Similarly, the overall survival findings showed slight, but non–statistically significant improvement in the rituximab arms (HR, 0.9; P = .39). The 3-year and median overall survival outcomes appeared to favor rituximab, but “this was not the magnitude of benefit that we were seeking in our study,” she said.

However, while a preplanned subgroup analysis by cytogenetic and other risk groups, as well as by cell surface CD20 expression, did not reveal any significant interactions for EFS, they did show that the percentage of blasts expressing CD20 was a strong independent poor prognostic factor.

A cutoff of 11.6%, compared with the 20% typically used, was found to be ideal based on the Youden Index, which determines the best balance between sensitivity and specificity.

“Interestingly, in addition to this, we did not find any impact of CD20 expression on response to rituximab,” Dr. Fielding noted.

Further, outcomes analyses by post–induction treatment assignment showed that, in patients who received myeloablative allogeneic stem cell transplant, “there was a large and statistically significant benefit to [adding rituximab], she said.

Landmark analysis showed an EFS hazard ratio of 0.48 at the time of transplant (P = .037), she said, noting that the SOC and SOC plus rituximab arms were well matched among this subset of patients.

The difference appeared to relate to relapse risk (HR, .38), but on an intention-to-treat analysis including all patients under age 40 years, the difference was “no longer quite so pronounced.”

“We do not understand the biological basis for this finding,” Dr. Fielding said, noting that it wasn’t explained by differences in graft-versus-host disease or infection. “This difference was not apparent in patients who received or were intended to receive reduced-intensity allogeneic conditioning.”

A multivariable analysis did not show a significant treatment effect, but did show “the same trend toward a better outcome in the rituximab arm,” she added.

UKALL14 subjects were adults aged 25-65 years with de novo ALL, regardless of Ph status or cell surface CD20 expression, who were recruited from 70 centers in the United Kingdom between December 2010 and July 2017. Those randomized to standard of care received a standard four-drug induction after a steroid prephase – with or without four doses of rituximab.

After a second induction, patients underwent risk assessment; low-risk patients were treated on the SOC arm and received high-dose methotrexate and additional pegylated asparaginase followed by four cycles of consolidation therapy. This was followed by 2 years of maintenance treatment.

High-risk patients with a sibling or fully matched unrelated donor available underwent allogeneic stem cell transplant, with those aged 40 years and younger receiving myeloablative conditioning and those over 40 years receiving reduced-intensity conditioning.

Most patients in the SOC plus rituximab arm received all four doses of rituximab, and the treatment arms were well-balanced with respect to risk characteristics, Dr. Fielding said, adding that no differences were noted in adverse events or mortality between the arms.

There is strong rationale for studying rituximab in ALL, she noted. For example, rituximab is safe to add to chemotherapy, and it has potential relevance at any level of CD20 expression, she said, explaining the basis for the study. Indeed, the findings support its use in this setting.

“Rituximab benefits patients with ALL,” she said. “But in our hands, four doses is insufficient to realize the full benefit.”

Dr. Fielding is a consultant for Amgen, Novartis, Pfizer, and Incyte.

sworcester@mdedge.com

SOURCE: Marks D et al. ASH 2019, Abstract 739.

ORLANDO – Adding rituximab to standard induction chemotherapy in adults with precursor B-cell acute lymphoblastic leukemia (B-ALL) appears to improve event-free survival, but four doses are insufficient, according to the first analysis from the randomized, phase 3 UKALL14 trial.

VashiDonsk/Creative Commons/CC ASA 3.0

The findings also suggest that the significant event-free survival (EFS) benefit of adding 16-18 doses of rituximab in B-ALL patients, as demonstrated in “the recent and very important” GRAALL-2005/R study, may be generalizable to B-precursor ALL patients regardless of Philadelphia (Ph) chromosome status or CD20-positive expression level, Adele K. Fielding, MBBS, PhD, reported at the annual meeting of the American Society of Hematology.

Unlike GRAALL-2005/R (NCT00327678), which included only patients with greater than 20% of ALL blasts expressing CD20 and with Ph-negative ALL, UKALL14 (NCT01085617) included B-ALL patients regardless of Ph chromosome status or CD20 expression level, explained Dr. Fielding of the Cancer Institute, University College London.

Overall, EFS rates among patients in the UKALL14 study at a median follow-up of 40.5 months were 41.9% in 288 patients randomized to receive standard-of-care chemotherapy (SOC), and 48.7% among 289 randomized to receive SOC plus rituximab, but the difference was not statistically significant (hazard ratio, 0.88; P = .28), she said.

“Likewise there was a nonsignificant improvement in 3-year event-free survival and in median event-free survival in the rituximab arms, but these differences did not meet our predetermined criteria,” she added.

Similarly, the overall survival findings showed slight, but non–statistically significant improvement in the rituximab arms (HR, 0.9; P = .39). The 3-year and median overall survival outcomes appeared to favor rituximab, but “this was not the magnitude of benefit that we were seeking in our study,” she said.

However, while a preplanned subgroup analysis by cytogenetic and other risk groups, as well as by cell surface CD20 expression, did not reveal any significant interactions for EFS, they did show that the percentage of blasts expressing CD20 was a strong independent poor prognostic factor.

A cutoff of 11.6%, compared with the 20% typically used, was found to be ideal based on the Youden Index, which determines the best balance between sensitivity and specificity.

“Interestingly, in addition to this, we did not find any impact of CD20 expression on response to rituximab,” Dr. Fielding noted.

Further, outcomes analyses by post–induction treatment assignment showed that, in patients who received myeloablative allogeneic stem cell transplant, “there was a large and statistically significant benefit to [adding rituximab], she said.

Landmark analysis showed an EFS hazard ratio of 0.48 at the time of transplant (P = .037), she said, noting that the SOC and SOC plus rituximab arms were well matched among this subset of patients.

The difference appeared to relate to relapse risk (HR, .38), but on an intention-to-treat analysis including all patients under age 40 years, the difference was “no longer quite so pronounced.”

“We do not understand the biological basis for this finding,” Dr. Fielding said, noting that it wasn’t explained by differences in graft-versus-host disease or infection. “This difference was not apparent in patients who received or were intended to receive reduced-intensity allogeneic conditioning.”

A multivariable analysis did not show a significant treatment effect, but did show “the same trend toward a better outcome in the rituximab arm,” she added.

UKALL14 subjects were adults aged 25-65 years with de novo ALL, regardless of Ph status or cell surface CD20 expression, who were recruited from 70 centers in the United Kingdom between December 2010 and July 2017. Those randomized to standard of care received a standard four-drug induction after a steroid prephase – with or without four doses of rituximab.

After a second induction, patients underwent risk assessment; low-risk patients were treated on the SOC arm and received high-dose methotrexate and additional pegylated asparaginase followed by four cycles of consolidation therapy. This was followed by 2 years of maintenance treatment.

High-risk patients with a sibling or fully matched unrelated donor available underwent allogeneic stem cell transplant, with those aged 40 years and younger receiving myeloablative conditioning and those over 40 years receiving reduced-intensity conditioning.

Most patients in the SOC plus rituximab arm received all four doses of rituximab, and the treatment arms were well-balanced with respect to risk characteristics, Dr. Fielding said, adding that no differences were noted in adverse events or mortality between the arms.

There is strong rationale for studying rituximab in ALL, she noted. For example, rituximab is safe to add to chemotherapy, and it has potential relevance at any level of CD20 expression, she said, explaining the basis for the study. Indeed, the findings support its use in this setting.

“Rituximab benefits patients with ALL,” she said. “But in our hands, four doses is insufficient to realize the full benefit.”

Dr. Fielding is a consultant for Amgen, Novartis, Pfizer, and Incyte.

sworcester@mdedge.com

SOURCE: Marks D et al. ASH 2019, Abstract 739.

Prescription pricing is a primary reason why Medicaid spending on multiple sclerosis disease-modifying therapies (DMTs) has more than doubled between 2011 and 2017 and the introduction of a generic glatiramer acetate is having nominal effect on pricing and utilization within the class, new research is showing.

Kenishirotie/Thinkstock

“Gross spending on self-administered and infusible MS DMTs in the Medicaid program increased 2.9-fold from $453 million in 2011 to $1.32 billion in 2017,” Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues wrote in a research report published Jan. 15 in Neurology. Net spending after accounting for rebates during this period showed a doubling of spending from $278 million per year to $600 million per year.

Use of MS DMTs during this period overall remained stable, but there was a shift from injectable DMTs to oral DMTs during this time window, the researchers found, with the plurality of utilization attributed to glatiramer acetate.

Sandoz began marketing a generic version of glatiramer acetate 20 mg in the second quarter of 2015, which led to an immediate increase in the cost per prescription of $441 for the branded version of glatiramer acetate 20 mg, although that cost has come down gradually by $52 per prescription over time. Other DMTs saw minimal price changes at that time, Dr. Hartung and his colleagues noted.

The researchers attributed the increased Medicaid spending to rising prices of DMTs.

“Although some of this increase is attributable to the 2014 Medicaid expansion, the primary driver was rising DMT costs per prescription, which doubled over the period,” the researchers wrote. “Thus, we assert that rising prices, not increasing use, are the primary driver of spending for DMTs in the Medicaid program.”

In addition, the introduction of the first generic DMT “appeared to have little effect on the overall trajectory of DMT costs,” they continued. “In fact, the cost of Teva’s 20-mg glatiramer acetate increased significantly following the release of Sandoz’s generic. ... The increase possibly signified efforts to both retain revenue and further push market share to the 40-mg version. Although the costs for generic glatiramer acetate declined over time, its introduction appears not to have fundamentally affected the overall trend in DMT costs.”

Indeed, the researchers’ examination of utilization trends found that Teva executed a successful preemptive strategy of converting 20-mg users of glatiramer acetate to 40-mg users, something that is not interchangeable with the generic product.

“Low generic penetration is also due to the fact that Sandoz’s product was only 15% less expensive than branded glatiramer acetate 20 mg and approximately the same cost as the 40-mg version at launch,” Dr. Hartung and his colleagues stated. “This difference may have been further diminished by rebates that Teva may have provided to maintain preferred status on state Medicaid formularies.”

These factors reflect an “urgent need for robust generic competition within the DMT class,” the authors wrote.

The study was supported by the National Multiple Sclerosis Society. Lead author Dr. Hartung reported receiving research support from AbbVie.

gtwachtman@mdedge.com

SOURCE: Hartung D et al. Neurology. Jan 15. doi: 10.1212/WNL.0000000000008936.

Prescription pricing is a primary reason why Medicaid spending on multiple sclerosis disease-modifying therapies (DMTs) has more than doubled between 2011 and 2017 and the introduction of a generic glatiramer acetate is having nominal effect on pricing and utilization within the class, new research is showing.

Kenishirotie/Thinkstock

“Gross spending on self-administered and infusible MS DMTs in the Medicaid program increased 2.9-fold from $453 million in 2011 to $1.32 billion in 2017,” Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues wrote in a research report published Jan. 15 in Neurology. Net spending after accounting for rebates during this period showed a doubling of spending from $278 million per year to $600 million per year.

Use of MS DMTs during this period overall remained stable, but there was a shift from injectable DMTs to oral DMTs during this time window, the researchers found, with the plurality of utilization attributed to glatiramer acetate.

Sandoz began marketing a generic version of glatiramer acetate 20 mg in the second quarter of 2015, which led to an immediate increase in the cost per prescription of $441 for the branded version of glatiramer acetate 20 mg, although that cost has come down gradually by $52 per prescription over time. Other DMTs saw minimal price changes at that time, Dr. Hartung and his colleagues noted.

The researchers attributed the increased Medicaid spending to rising prices of DMTs.

“Although some of this increase is attributable to the 2014 Medicaid expansion, the primary driver was rising DMT costs per prescription, which doubled over the period,” the researchers wrote. “Thus, we assert that rising prices, not increasing use, are the primary driver of spending for DMTs in the Medicaid program.”

In addition, the introduction of the first generic DMT “appeared to have little effect on the overall trajectory of DMT costs,” they continued. “In fact, the cost of Teva’s 20-mg glatiramer acetate increased significantly following the release of Sandoz’s generic. ... The increase possibly signified efforts to both retain revenue and further push market share to the 40-mg version. Although the costs for generic glatiramer acetate declined over time, its introduction appears not to have fundamentally affected the overall trend in DMT costs.”

Indeed, the researchers’ examination of utilization trends found that Teva executed a successful preemptive strategy of converting 20-mg users of glatiramer acetate to 40-mg users, something that is not interchangeable with the generic product.

“Low generic penetration is also due to the fact that Sandoz’s product was only 15% less expensive than branded glatiramer acetate 20 mg and approximately the same cost as the 40-mg version at launch,” Dr. Hartung and his colleagues stated. “This difference may have been further diminished by rebates that Teva may have provided to maintain preferred status on state Medicaid formularies.”

These factors reflect an “urgent need for robust generic competition within the DMT class,” the authors wrote.

The study was supported by the National Multiple Sclerosis Society. Lead author Dr. Hartung reported receiving research support from AbbVie.

gtwachtman@mdedge.com

SOURCE: Hartung D et al. Neurology. Jan 15. doi: 10.1212/WNL.0000000000008936.

Prescription pricing is a primary reason why Medicaid spending on multiple sclerosis disease-modifying therapies (DMTs) has more than doubled between 2011 and 2017 and the introduction of a generic glatiramer acetate is having nominal effect on pricing and utilization within the class, new research is showing.

Kenishirotie/Thinkstock

“Gross spending on self-administered and infusible MS DMTs in the Medicaid program increased 2.9-fold from $453 million in 2011 to $1.32 billion in 2017,” Daniel Hartung, PharmD, of Oregon Health and Science University, Portland, and his colleagues wrote in a research report published Jan. 15 in Neurology. Net spending after accounting for rebates during this period showed a doubling of spending from $278 million per year to $600 million per year.

Use of MS DMTs during this period overall remained stable, but there was a shift from injectable DMTs to oral DMTs during this time window, the researchers found, with the plurality of utilization attributed to glatiramer acetate.

Sandoz began marketing a generic version of glatiramer acetate 20 mg in the second quarter of 2015, which led to an immediate increase in the cost per prescription of $441 for the branded version of glatiramer acetate 20 mg, although that cost has come down gradually by $52 per prescription over time. Other DMTs saw minimal price changes at that time, Dr. Hartung and his colleagues noted.

The researchers attributed the increased Medicaid spending to rising prices of DMTs.

“Although some of this increase is attributable to the 2014 Medicaid expansion, the primary driver was rising DMT costs per prescription, which doubled over the period,” the researchers wrote. “Thus, we assert that rising prices, not increasing use, are the primary driver of spending for DMTs in the Medicaid program.”

In addition, the introduction of the first generic DMT “appeared to have little effect on the overall trajectory of DMT costs,” they continued. “In fact, the cost of Teva’s 20-mg glatiramer acetate increased significantly following the release of Sandoz’s generic. ... The increase possibly signified efforts to both retain revenue and further push market share to the 40-mg version. Although the costs for generic glatiramer acetate declined over time, its introduction appears not to have fundamentally affected the overall trend in DMT costs.”

Indeed, the researchers’ examination of utilization trends found that Teva executed a successful preemptive strategy of converting 20-mg users of glatiramer acetate to 40-mg users, something that is not interchangeable with the generic product.

“Low generic penetration is also due to the fact that Sandoz’s product was only 15% less expensive than branded glatiramer acetate 20 mg and approximately the same cost as the 40-mg version at launch,” Dr. Hartung and his colleagues stated. “This difference may have been further diminished by rebates that Teva may have provided to maintain preferred status on state Medicaid formularies.”

These factors reflect an “urgent need for robust generic competition within the DMT class,” the authors wrote.

The study was supported by the National Multiple Sclerosis Society. Lead author Dr. Hartung reported receiving research support from AbbVie.

gtwachtman@mdedge.com

SOURCE: Hartung D et al. Neurology. Jan 15. doi: 10.1212/WNL.0000000000008936.

Sleeve gastrectomy was associated with significantly fewer postsurgical interventions and operations than was Roux-en-Y gastric bypass over longer-term follow-up in a recent cohort study based on real-world clinical data, according to investigators.

Interventions, operations, and hospitalizations were “relatively common” for both procedures over the 5-year follow-up, though significantly less so with sleeve gastrectomy, which has become the most common bariatric operation, the investigators said in a recent report on the study.

The benefit of sleeve gastrectomy seemed to be most pronounced in patients with lower body mass index and those with fewer comorbidities, according to the authors of the report, led by bariatric and general surgeon Anita Courcoulas, MD, of the University of Pittsburgh Medical Center.

That finding is counterintuitive, since in clinical practice, sleeve gastrectomy is frequently thought of as the preferred procedure for individuals with higher BMI or more comorbidities, though Dr. Courcoulas and colleagues cautioned that the findings were “exploratory” and require further investigation. Historically, Roux-en-Y gastric bypass provided more weight loss.

Safety results from this study, balanced by weight loss and health outcomes data, will “help inform procedure-specific decision making for prospective patients and physicians,” said Dr. Courcoulas and coauthors of the report, which appears in JAMA Surgery.

The study included 33,560 adults who had undergone the Roux-en-Y procedure or sleeve gastrectomy, making it one of the largest bariatric cohort studies ever to be done, according to the investigators.

The majority of patients in the study (54%) underwent Roux-en-Y gastric bypass, though the number of sleeve gastrectomy procedures increased each year in the study, which included patients who underwent a primary bariatric surgery procedure between January 2005 and September 2015 at 1 of 10 sites in the National Patient-Centered Clinical Research Network.

Most of the patients were female (80%) and white (66%), and 26% were Hispanic, according to the researchers, who said their study was more racially diverse than other bariatric studies, and therefore potentially more generalizable to real-world clinical practice.

Over the 5-year follow-up period, patients who underwent sleeve gastrectomy were less likely to subsequently undergo operations involving the abdomen, or interventions for enteral access, such as placement of gastrostomy tubes, according to the investigators, who reported a hazard ratio (HR) of 0.72 (95% confidence interval [CI], 0.65-0.79; P less than .001).

The estimated cumulative rate of operations or interventions at 5 years was 8.94% (95% CI, 8.23%-9.65%) for the patients who underwent sleeve gastrectomy, compared with 12.27% (95% CI, 11.49%-13.05%) for those who underwent the Roux-en-Y procedure, according to the report.

Hospitalization was also less likely for sleeve gastrectomy versus Roux-en-Y gastric bypass, with a hazard ratio of 0.82 and estimated cumulative incidence rates of 32.79% and 38.33%, respectively. Likewise, endoscopy was less likely in the sleeve gastrectomy group.

All-cause mortality did not differ between the groups at this 5-year follow-up, the investigators said.

“The present data were gathered from clinical care in the real world, yet the results are comparable to controlled studies and therefore lend additional support to the findings of these other types of studies that operation and intervention occur less commonly after sleeve gastrectomy than after Roux-en-Y gastric bypass for up to 5 years,” Dr. Courcoulas and coauthors noted in a discussion of their results.

This work was funded by the Patient-Centered Outcomes Research Institute. Dr. Courcoulas reported receiving a grant from Allurion. Coauthors provided disclosures related to the National Institutes of Health, IFSO Latin America Chapter, and the Food and Drug Administration.

*This story was updated on January 16, 2020.

SOURCE: Courcoulas A et al. JAMA Surg. 2020 Jan 15. doi: 10.1001/jamasurg.2019.5470.

Sleeve gastrectomy was associated with significantly fewer postsurgical interventions and operations than was Roux-en-Y gastric bypass over longer-term follow-up in a recent cohort study based on real-world clinical data, according to investigators.

Interventions, operations, and hospitalizations were “relatively common” for both procedures over the 5-year follow-up, though significantly less so with sleeve gastrectomy, which has become the most common bariatric operation, the investigators said in a recent report on the study.

The benefit of sleeve gastrectomy seemed to be most pronounced in patients with lower body mass index and those with fewer comorbidities, according to the authors of the report, led by bariatric and general surgeon Anita Courcoulas, MD, of the University of Pittsburgh Medical Center.

That finding is counterintuitive, since in clinical practice, sleeve gastrectomy is frequently thought of as the preferred procedure for individuals with higher BMI or more comorbidities, though Dr. Courcoulas and colleagues cautioned that the findings were “exploratory” and require further investigation. Historically, Roux-en-Y gastric bypass provided more weight loss.

Safety results from this study, balanced by weight loss and health outcomes data, will “help inform procedure-specific decision making for prospective patients and physicians,” said Dr. Courcoulas and coauthors of the report, which appears in JAMA Surgery.

The study included 33,560 adults who had undergone the Roux-en-Y procedure or sleeve gastrectomy, making it one of the largest bariatric cohort studies ever to be done, according to the investigators.

The majority of patients in the study (54%) underwent Roux-en-Y gastric bypass, though the number of sleeve gastrectomy procedures increased each year in the study, which included patients who underwent a primary bariatric surgery procedure between January 2005 and September 2015 at 1 of 10 sites in the National Patient-Centered Clinical Research Network.

Most of the patients were female (80%) and white (66%), and 26% were Hispanic, according to the researchers, who said their study was more racially diverse than other bariatric studies, and therefore potentially more generalizable to real-world clinical practice.

Over the 5-year follow-up period, patients who underwent sleeve gastrectomy were less likely to subsequently undergo operations involving the abdomen, or interventions for enteral access, such as placement of gastrostomy tubes, according to the investigators, who reported a hazard ratio (HR) of 0.72 (95% confidence interval [CI], 0.65-0.79; P less than .001).

The estimated cumulative rate of operations or interventions at 5 years was 8.94% (95% CI, 8.23%-9.65%) for the patients who underwent sleeve gastrectomy, compared with 12.27% (95% CI, 11.49%-13.05%) for those who underwent the Roux-en-Y procedure, according to the report.

Hospitalization was also less likely for sleeve gastrectomy versus Roux-en-Y gastric bypass, with a hazard ratio of 0.82 and estimated cumulative incidence rates of 32.79% and 38.33%, respectively. Likewise, endoscopy was less likely in the sleeve gastrectomy group.

All-cause mortality did not differ between the groups at this 5-year follow-up, the investigators said.

“The present data were gathered from clinical care in the real world, yet the results are comparable to controlled studies and therefore lend additional support to the findings of these other types of studies that operation and intervention occur less commonly after sleeve gastrectomy than after Roux-en-Y gastric bypass for up to 5 years,” Dr. Courcoulas and coauthors noted in a discussion of their results.

This work was funded by the Patient-Centered Outcomes Research Institute. Dr. Courcoulas reported receiving a grant from Allurion. Coauthors provided disclosures related to the National Institutes of Health, IFSO Latin America Chapter, and the Food and Drug Administration.

*This story was updated on January 16, 2020.

SOURCE: Courcoulas A et al. JAMA Surg. 2020 Jan 15. doi: 10.1001/jamasurg.2019.5470.

Sleeve gastrectomy was associated with significantly fewer postsurgical interventions and operations than was Roux-en-Y gastric bypass over longer-term follow-up in a recent cohort study based on real-world clinical data, according to investigators.

Interventions, operations, and hospitalizations were “relatively common” for both procedures over the 5-year follow-up, though significantly less so with sleeve gastrectomy, which has become the most common bariatric operation, the investigators said in a recent report on the study.

The benefit of sleeve gastrectomy seemed to be most pronounced in patients with lower body mass index and those with fewer comorbidities, according to the authors of the report, led by bariatric and general surgeon Anita Courcoulas, MD, of the University of Pittsburgh Medical Center.

That finding is counterintuitive, since in clinical practice, sleeve gastrectomy is frequently thought of as the preferred procedure for individuals with higher BMI or more comorbidities, though Dr. Courcoulas and colleagues cautioned that the findings were “exploratory” and require further investigation. Historically, Roux-en-Y gastric bypass provided more weight loss.

Safety results from this study, balanced by weight loss and health outcomes data, will “help inform procedure-specific decision making for prospective patients and physicians,” said Dr. Courcoulas and coauthors of the report, which appears in JAMA Surgery.

The study included 33,560 adults who had undergone the Roux-en-Y procedure or sleeve gastrectomy, making it one of the largest bariatric cohort studies ever to be done, according to the investigators.

The majority of patients in the study (54%) underwent Roux-en-Y gastric bypass, though the number of sleeve gastrectomy procedures increased each year in the study, which included patients who underwent a primary bariatric surgery procedure between January 2005 and September 2015 at 1 of 10 sites in the National Patient-Centered Clinical Research Network.

Most of the patients were female (80%) and white (66%), and 26% were Hispanic, according to the researchers, who said their study was more racially diverse than other bariatric studies, and therefore potentially more generalizable to real-world clinical practice.

Over the 5-year follow-up period, patients who underwent sleeve gastrectomy were less likely to subsequently undergo operations involving the abdomen, or interventions for enteral access, such as placement of gastrostomy tubes, according to the investigators, who reported a hazard ratio (HR) of 0.72 (95% confidence interval [CI], 0.65-0.79; P less than .001).

The estimated cumulative rate of operations or interventions at 5 years was 8.94% (95% CI, 8.23%-9.65%) for the patients who underwent sleeve gastrectomy, compared with 12.27% (95% CI, 11.49%-13.05%) for those who underwent the Roux-en-Y procedure, according to the report.

Hospitalization was also less likely for sleeve gastrectomy versus Roux-en-Y gastric bypass, with a hazard ratio of 0.82 and estimated cumulative incidence rates of 32.79% and 38.33%, respectively. Likewise, endoscopy was less likely in the sleeve gastrectomy group.

All-cause mortality did not differ between the groups at this 5-year follow-up, the investigators said.

“The present data were gathered from clinical care in the real world, yet the results are comparable to controlled studies and therefore lend additional support to the findings of these other types of studies that operation and intervention occur less commonly after sleeve gastrectomy than after Roux-en-Y gastric bypass for up to 5 years,” Dr. Courcoulas and coauthors noted in a discussion of their results.

This work was funded by the Patient-Centered Outcomes Research Institute. Dr. Courcoulas reported receiving a grant from Allurion. Coauthors provided disclosures related to the National Institutes of Health, IFSO Latin America Chapter, and the Food and Drug Administration.

*This story was updated on January 16, 2020.

SOURCE: Courcoulas A et al. JAMA Surg. 2020 Jan 15. doi: 10.1001/jamasurg.2019.5470.