Musculoskeletal Disorders

TOPLINE:

Higher scores on the dietary inflammatory index in patients with knee osteoarthritis (KOA) were associated with an increased risk of experiencing greater pain over 10 years of follow-up.

METHODOLOGY:

• The researchers recruited 944 adults aged 50-80 years from the community; the mean age at baseline was 62.9 years, 51% were female, the mean body mass index was 27.9 kg/m2, and 60% had radiographic KOA at baseline.
• Magnetic resonance imaging was used to identify structural changes in the knee based on cartilage volume and bone marrow lesions at baseline and follow-up; knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire.
• Dietary inflammation was measured using energy-adjusted dietary inflammatory index (E-DII) scores based on nutritional information from the Food-Frequency Questionnaire (FFQ).

TAKEAWAY: 

• Over a follow-up period of 10.7 years, higher E-DII scores were positively associated with increased pain scores (beta = 0.21) after adjustment for age, sex, body mass index, steps per day, education, emotional problems, employment status, comorbidities, and radiographic KOA.
• E-DII scores were not associated with tibial cartilage volume loss or overall bone marrow loss.
• Patients with higher E-DII scores had a significantly higher risk of being on a moderate pain trajectory (relative risk ratio, 1.19), compared with those who followed a minimal pain trajectory over the follow-up period.

IN PRACTICE:

“An anti-inflammatory diet may reduce pain among KOA patients. Future trials investigating the potential of an anti-inflammatory diet for pain relief in KOA are warranted,” the researchers wrote. 

SOURCE:

The lead author on the study was Canchen Ma, PhD, of the University of Tasmania, Hobart, Australia. The study was published online in Arthritis Care & Research. 

LIMITATIONS:

The study used a relatively small number of nutrients from the FFQ to calculate the E-DII scores; participants also exhibited a narrower range of E-DII scores than previous studies. The researchers were unable to account for pharmacologic or preventive treatments. 

DISCLOSURES:

The study was supported by the National Health and Medical Research Council of Australia (NHMRC) and Arthritis Australia. Several authors received support from the National Heart Foundation Fellowship, the NHMRC Leadership Fellowship, the NHMRC Practitioner Fellowship, and the NHMRC Early Career Fellowship. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher scores on the dietary inflammatory index in patients with knee osteoarthritis (KOA) were associated with an increased risk of experiencing greater pain over 10 years of follow-up.

METHODOLOGY:

• The researchers recruited 944 adults aged 50-80 years from the community; the mean age at baseline was 62.9 years, 51% were female, the mean body mass index was 27.9 kg/m2, and 60% had radiographic KOA at baseline.
• Magnetic resonance imaging was used to identify structural changes in the knee based on cartilage volume and bone marrow lesions at baseline and follow-up; knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire.
• Dietary inflammation was measured using energy-adjusted dietary inflammatory index (E-DII) scores based on nutritional information from the Food-Frequency Questionnaire (FFQ).

TAKEAWAY: 

• Over a follow-up period of 10.7 years, higher E-DII scores were positively associated with increased pain scores (beta = 0.21) after adjustment for age, sex, body mass index, steps per day, education, emotional problems, employment status, comorbidities, and radiographic KOA.
• E-DII scores were not associated with tibial cartilage volume loss or overall bone marrow loss.
• Patients with higher E-DII scores had a significantly higher risk of being on a moderate pain trajectory (relative risk ratio, 1.19), compared with those who followed a minimal pain trajectory over the follow-up period.

IN PRACTICE:

“An anti-inflammatory diet may reduce pain among KOA patients. Future trials investigating the potential of an anti-inflammatory diet for pain relief in KOA are warranted,” the researchers wrote. 

SOURCE:

The lead author on the study was Canchen Ma, PhD, of the University of Tasmania, Hobart, Australia. The study was published online in Arthritis Care & Research. 

LIMITATIONS:

The study used a relatively small number of nutrients from the FFQ to calculate the E-DII scores; participants also exhibited a narrower range of E-DII scores than previous studies. The researchers were unable to account for pharmacologic or preventive treatments. 

DISCLOSURES:

The study was supported by the National Health and Medical Research Council of Australia (NHMRC) and Arthritis Australia. Several authors received support from the National Heart Foundation Fellowship, the NHMRC Leadership Fellowship, the NHMRC Practitioner Fellowship, and the NHMRC Early Career Fellowship. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher scores on the dietary inflammatory index in patients with knee osteoarthritis (KOA) were associated with an increased risk of experiencing greater pain over 10 years of follow-up.

METHODOLOGY:

• The researchers recruited 944 adults aged 50-80 years from the community; the mean age at baseline was 62.9 years, 51% were female, the mean body mass index was 27.9 kg/m2, and 60% had radiographic KOA at baseline.
• Magnetic resonance imaging was used to identify structural changes in the knee based on cartilage volume and bone marrow lesions at baseline and follow-up; knee pain was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire.
• Dietary inflammation was measured using energy-adjusted dietary inflammatory index (E-DII) scores based on nutritional information from the Food-Frequency Questionnaire (FFQ).

TAKEAWAY: 

• Over a follow-up period of 10.7 years, higher E-DII scores were positively associated with increased pain scores (beta = 0.21) after adjustment for age, sex, body mass index, steps per day, education, emotional problems, employment status, comorbidities, and radiographic KOA.
• E-DII scores were not associated with tibial cartilage volume loss or overall bone marrow loss.
• Patients with higher E-DII scores had a significantly higher risk of being on a moderate pain trajectory (relative risk ratio, 1.19), compared with those who followed a minimal pain trajectory over the follow-up period.

IN PRACTICE:

“An anti-inflammatory diet may reduce pain among KOA patients. Future trials investigating the potential of an anti-inflammatory diet for pain relief in KOA are warranted,” the researchers wrote. 

SOURCE:

The lead author on the study was Canchen Ma, PhD, of the University of Tasmania, Hobart, Australia. The study was published online in Arthritis Care & Research. 

LIMITATIONS:

The study used a relatively small number of nutrients from the FFQ to calculate the E-DII scores; participants also exhibited a narrower range of E-DII scores than previous studies. The researchers were unable to account for pharmacologic or preventive treatments. 

DISCLOSURES:

The study was supported by the National Health and Medical Research Council of Australia (NHMRC) and Arthritis Australia. Several authors received support from the National Heart Foundation Fellowship, the NHMRC Leadership Fellowship, the NHMRC Practitioner Fellowship, and the NHMRC Early Career Fellowship. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Wearing a brace at night is an effective alternative for moderate adolescent idiopathic scoliosis (AIS) if the patient rejects wearing a brace full time, new research suggests.

In the randomized Conservative Treatment for Adolescent Idiopathic Scoliosis (CONTRAIS) trial, researchers, led by Anastasios Charalampidis, MD, PhD, with the Department of Clinical Science, Intervention and Technology at Karolinska Institutet in Stockholm, Sweden, tested whether a group using self-managed physical activity combined with either nighttime bracing for 8 hours or scoliosis-specific exercise achieved better results than a control group doing self-managed physical activity alone for 1 hour per day in preventing Cobb angle progression in moderate-grade AIS.

Findings of the trial, conducted in 6 public hospitals across Sweden, were published online in JAMA Network Open.
 

Night Bracing More Effective Than Comparison Arms

In the trial of 135 patients, aged 9-17 years, who were skeletally immature with moderate AIS, researchers found that night bracing plus self-managed physical activity prevented curve progression of more than 6 degrees (treatment success) to a significantly greater extent than did either self-managed physical activity alone or scoliosis-specific exercise.

A secondary outcome of curve progression was the number of patients who had surgery up until 2 years after the primary outcome.

The average age of patients was 12.7 years and most (82%) were female. Patients with treatment failure (curve progression of more than 6 degrees) had the option to transition to a full-time brace until skeletal maturity. That option resulted in similar frequency of surgery independent of initial treatment, according to the paper.

AIS is a structural deformity of the spinal column, affecting otherwise healthy children and adolescents during their growth spurt.

Previous studies have suggested that full-time bracing is effective in treating moderate-grade AIS. But the physical distress and psychological side effects that some experience can cause low adherence or rejection of the treatment.

The authors wrote that, “To our knowledge, there have been no randomized clinical trials investigating night bracing versus a control group.”

In this trial, treatment success was seen in 34 of 45 patients (76%) in the nighttime-bracing group and in 24 of 45 patients (53%) in the physical activity–alone group (odds ratio [OR], 2.7; 95% CI, 1.1-6.6). Success occurred in 26 of 45 patients (58%) in the scoliosis-specific exercise group (OR for scoliosis-specific exercise vs physical activity alone, 1.2; 95% CI, 0.5-2.8).
 

Adverse Events

Patients and clinicians could respond to an open-ended question regarding adverse events at each 6-month follow-up. Nineteen adverse events were reported in 15 patients between the start of the study up until the primary outcome was reached.

In the night-bracing group, there were 16 adverse events reported among 12 patients. They were: trunk pressure and skin problems (n = 10); sleeping problems (n = 2); emotional problems (n = 1); shoulder/neck pain (n = 2); and unspecified AEs (n = 1). In the scoliosis-specific exercise group, 3 adverse events were reported in 3 patients (pain during treatment (n = 1), muscle strain (n = 1), and low back pain (n = 1). No adverse events were reported in the physical activity alone group.

In an invited commentary, Kosei Nagata, MD, PhD, with the Department of Orthopaedic Surgery and Spinal Surgery at The University of Tokyo Hospital in Tokyo, Japan, said the study makes two important points.

“First, it was reaffirmed that the basis of scoliosis treatment is bracing and not a specific exercise therapy,” he wrote. “Second, nighttime bracing can be an effective alternative intervention for patients rejecting full-time bracing.”

He emphasized, however, that nighttime bracing alone is not enough to achieve success. In this study, bracing was combined with exercise. And the number of hours worn is important.

“Physicians should explain to patients with AIS and to their guardians the significant association between hours of brace wear and treatment success,” Dr. Nagata wrote. He pointed out that, in a previous randomized clinical trial in 2013 by Weinstein et al., patients were instructed to wear a brace for at least 18 hours a day. The treatment success rates of brace-wearing patients were 40% for less than 6 hours each day; 70% for 6-12 hours each day, and 90% for more than 13 hours each day, which suggests that full-time bracing is optimal.

However, he added that physicians should keep in mind the sensitivities of youth and effect on their self-esteem when prescribing bracing, as many adolescents will have a fear of ridicule.

“The goals of bracing treatment for AIS are manifold: avoiding surgical treatment, preventing future back pain, maintaining respiratory function, and reducing the psychological impact of the deformity,” Dr. Nagata wrote. “Physicians should understand these aspects and take a balanced view of patients who refuse full-time bracing.”

He added that future improvements in design of the braces and less rigid alternatives will be important.

The trial was funded by the Swedish Research Council and by the Stockholm County Council, the Swedish Society of Spinal Surgeons, the Karolinska Institutet and the Crown Princess Lovisas Foundation. Study coauthor Paul Gerdhem, MD, PhD, reports grants from the Karolinska Institutet beyond his usual salary during the study and personal fees for lectures from DePuy Synthes and grants from Philips Healthcare paid to the institution outside the submitted work. No other disclosures were reported. Dr. Nagata reported no relevant financial relationships.

Wearing a brace at night is an effective alternative for moderate adolescent idiopathic scoliosis (AIS) if the patient rejects wearing a brace full time, new research suggests.

In the randomized Conservative Treatment for Adolescent Idiopathic Scoliosis (CONTRAIS) trial, researchers, led by Anastasios Charalampidis, MD, PhD, with the Department of Clinical Science, Intervention and Technology at Karolinska Institutet in Stockholm, Sweden, tested whether a group using self-managed physical activity combined with either nighttime bracing for 8 hours or scoliosis-specific exercise achieved better results than a control group doing self-managed physical activity alone for 1 hour per day in preventing Cobb angle progression in moderate-grade AIS.

Findings of the trial, conducted in 6 public hospitals across Sweden, were published online in JAMA Network Open.
 

Night Bracing More Effective Than Comparison Arms

In the trial of 135 patients, aged 9-17 years, who were skeletally immature with moderate AIS, researchers found that night bracing plus self-managed physical activity prevented curve progression of more than 6 degrees (treatment success) to a significantly greater extent than did either self-managed physical activity alone or scoliosis-specific exercise.

A secondary outcome of curve progression was the number of patients who had surgery up until 2 years after the primary outcome.

The average age of patients was 12.7 years and most (82%) were female. Patients with treatment failure (curve progression of more than 6 degrees) had the option to transition to a full-time brace until skeletal maturity. That option resulted in similar frequency of surgery independent of initial treatment, according to the paper.

AIS is a structural deformity of the spinal column, affecting otherwise healthy children and adolescents during their growth spurt.

Previous studies have suggested that full-time bracing is effective in treating moderate-grade AIS. But the physical distress and psychological side effects that some experience can cause low adherence or rejection of the treatment.

The authors wrote that, “To our knowledge, there have been no randomized clinical trials investigating night bracing versus a control group.”

In this trial, treatment success was seen in 34 of 45 patients (76%) in the nighttime-bracing group and in 24 of 45 patients (53%) in the physical activity–alone group (odds ratio [OR], 2.7; 95% CI, 1.1-6.6). Success occurred in 26 of 45 patients (58%) in the scoliosis-specific exercise group (OR for scoliosis-specific exercise vs physical activity alone, 1.2; 95% CI, 0.5-2.8).
 

Adverse Events

Patients and clinicians could respond to an open-ended question regarding adverse events at each 6-month follow-up. Nineteen adverse events were reported in 15 patients between the start of the study up until the primary outcome was reached.

In the night-bracing group, there were 16 adverse events reported among 12 patients. They were: trunk pressure and skin problems (n = 10); sleeping problems (n = 2); emotional problems (n = 1); shoulder/neck pain (n = 2); and unspecified AEs (n = 1). In the scoliosis-specific exercise group, 3 adverse events were reported in 3 patients (pain during treatment (n = 1), muscle strain (n = 1), and low back pain (n = 1). No adverse events were reported in the physical activity alone group.

In an invited commentary, Kosei Nagata, MD, PhD, with the Department of Orthopaedic Surgery and Spinal Surgery at The University of Tokyo Hospital in Tokyo, Japan, said the study makes two important points.

“First, it was reaffirmed that the basis of scoliosis treatment is bracing and not a specific exercise therapy,” he wrote. “Second, nighttime bracing can be an effective alternative intervention for patients rejecting full-time bracing.”

He emphasized, however, that nighttime bracing alone is not enough to achieve success. In this study, bracing was combined with exercise. And the number of hours worn is important.

“Physicians should explain to patients with AIS and to their guardians the significant association between hours of brace wear and treatment success,” Dr. Nagata wrote. He pointed out that, in a previous randomized clinical trial in 2013 by Weinstein et al., patients were instructed to wear a brace for at least 18 hours a day. The treatment success rates of brace-wearing patients were 40% for less than 6 hours each day; 70% for 6-12 hours each day, and 90% for more than 13 hours each day, which suggests that full-time bracing is optimal.

However, he added that physicians should keep in mind the sensitivities of youth and effect on their self-esteem when prescribing bracing, as many adolescents will have a fear of ridicule.

“The goals of bracing treatment for AIS are manifold: avoiding surgical treatment, preventing future back pain, maintaining respiratory function, and reducing the psychological impact of the deformity,” Dr. Nagata wrote. “Physicians should understand these aspects and take a balanced view of patients who refuse full-time bracing.”

He added that future improvements in design of the braces and less rigid alternatives will be important.

The trial was funded by the Swedish Research Council and by the Stockholm County Council, the Swedish Society of Spinal Surgeons, the Karolinska Institutet and the Crown Princess Lovisas Foundation. Study coauthor Paul Gerdhem, MD, PhD, reports grants from the Karolinska Institutet beyond his usual salary during the study and personal fees for lectures from DePuy Synthes and grants from Philips Healthcare paid to the institution outside the submitted work. No other disclosures were reported. Dr. Nagata reported no relevant financial relationships.

Wearing a brace at night is an effective alternative for moderate adolescent idiopathic scoliosis (AIS) if the patient rejects wearing a brace full time, new research suggests.

In the randomized Conservative Treatment for Adolescent Idiopathic Scoliosis (CONTRAIS) trial, researchers, led by Anastasios Charalampidis, MD, PhD, with the Department of Clinical Science, Intervention and Technology at Karolinska Institutet in Stockholm, Sweden, tested whether a group using self-managed physical activity combined with either nighttime bracing for 8 hours or scoliosis-specific exercise achieved better results than a control group doing self-managed physical activity alone for 1 hour per day in preventing Cobb angle progression in moderate-grade AIS.

Findings of the trial, conducted in 6 public hospitals across Sweden, were published online in JAMA Network Open.
 

Night Bracing More Effective Than Comparison Arms

In the trial of 135 patients, aged 9-17 years, who were skeletally immature with moderate AIS, researchers found that night bracing plus self-managed physical activity prevented curve progression of more than 6 degrees (treatment success) to a significantly greater extent than did either self-managed physical activity alone or scoliosis-specific exercise.

A secondary outcome of curve progression was the number of patients who had surgery up until 2 years after the primary outcome.

The average age of patients was 12.7 years and most (82%) were female. Patients with treatment failure (curve progression of more than 6 degrees) had the option to transition to a full-time brace until skeletal maturity. That option resulted in similar frequency of surgery independent of initial treatment, according to the paper.

AIS is a structural deformity of the spinal column, affecting otherwise healthy children and adolescents during their growth spurt.

Previous studies have suggested that full-time bracing is effective in treating moderate-grade AIS. But the physical distress and psychological side effects that some experience can cause low adherence or rejection of the treatment.

The authors wrote that, “To our knowledge, there have been no randomized clinical trials investigating night bracing versus a control group.”

In this trial, treatment success was seen in 34 of 45 patients (76%) in the nighttime-bracing group and in 24 of 45 patients (53%) in the physical activity–alone group (odds ratio [OR], 2.7; 95% CI, 1.1-6.6). Success occurred in 26 of 45 patients (58%) in the scoliosis-specific exercise group (OR for scoliosis-specific exercise vs physical activity alone, 1.2; 95% CI, 0.5-2.8).
 

Adverse Events

Patients and clinicians could respond to an open-ended question regarding adverse events at each 6-month follow-up. Nineteen adverse events were reported in 15 patients between the start of the study up until the primary outcome was reached.

In the night-bracing group, there were 16 adverse events reported among 12 patients. They were: trunk pressure and skin problems (n = 10); sleeping problems (n = 2); emotional problems (n = 1); shoulder/neck pain (n = 2); and unspecified AEs (n = 1). In the scoliosis-specific exercise group, 3 adverse events were reported in 3 patients (pain during treatment (n = 1), muscle strain (n = 1), and low back pain (n = 1). No adverse events were reported in the physical activity alone group.

In an invited commentary, Kosei Nagata, MD, PhD, with the Department of Orthopaedic Surgery and Spinal Surgery at The University of Tokyo Hospital in Tokyo, Japan, said the study makes two important points.

“First, it was reaffirmed that the basis of scoliosis treatment is bracing and not a specific exercise therapy,” he wrote. “Second, nighttime bracing can be an effective alternative intervention for patients rejecting full-time bracing.”

He emphasized, however, that nighttime bracing alone is not enough to achieve success. In this study, bracing was combined with exercise. And the number of hours worn is important.

“Physicians should explain to patients with AIS and to their guardians the significant association between hours of brace wear and treatment success,” Dr. Nagata wrote. He pointed out that, in a previous randomized clinical trial in 2013 by Weinstein et al., patients were instructed to wear a brace for at least 18 hours a day. The treatment success rates of brace-wearing patients were 40% for less than 6 hours each day; 70% for 6-12 hours each day, and 90% for more than 13 hours each day, which suggests that full-time bracing is optimal.

However, he added that physicians should keep in mind the sensitivities of youth and effect on their self-esteem when prescribing bracing, as many adolescents will have a fear of ridicule.

“The goals of bracing treatment for AIS are manifold: avoiding surgical treatment, preventing future back pain, maintaining respiratory function, and reducing the psychological impact of the deformity,” Dr. Nagata wrote. “Physicians should understand these aspects and take a balanced view of patients who refuse full-time bracing.”

He added that future improvements in design of the braces and less rigid alternatives will be important.

The trial was funded by the Swedish Research Council and by the Stockholm County Council, the Swedish Society of Spinal Surgeons, the Karolinska Institutet and the Crown Princess Lovisas Foundation. Study coauthor Paul Gerdhem, MD, PhD, reports grants from the Karolinska Institutet beyond his usual salary during the study and personal fees for lectures from DePuy Synthes and grants from Philips Healthcare paid to the institution outside the submitted work. No other disclosures were reported. Dr. Nagata reported no relevant financial relationships.

Bone health begins in childhood, particularly during the rapid bone accrual phase of puberty, which is essential for attaining optimal peak bone mass. Peak bone mass is achieved in early adult life and affects both immediate and future fracture risk. Genetic, nutritional, exercise-related, and hormonal factors, and certain diseases and medications, have deleterious effects on bone health.

In addition, emerging data suggest that certain manmade chemicals known as per- and polyfluoroalkyl substances (PFAS) may affect bone accrual during this important period and potentially increase the risk for osteoporosis in adulthood. Osteoporosis refers to increased fracture risk because of low bone density and affects a large proportion of postmenopausal women and older men.

New evidence comes from a recent study conducted by investigators from the Keck School of Medicine, who examined the impact of exposure to PFAS on skeletal outcomes in youth. Of note, participants were primarily Hispanic; this population has a higher risk for osteoporosis in adulthood. PFAS are manmade chemicals with water- and grease-resistant properties. They are used in a variety of products, such as nonstick cookware, food packaging, water-repellent clothing, stain-resistant fabrics, carpets, and in certain industrial processes. They are pervasive in the environment, in wildlife, and in humans.

Use and production of certain PFAS, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA),  have decreased over the past two decades, with a significant reduction in blood concentrations of these chemicals. However, they can be resistant to degradation and have very long half-lives. As a consequence, these «forever chemicals» continue to linger in the environment. Also, the risk for exposure to other PFAS persists, and almost every individual has detectable levels of PFAS in blood.

Scientists are still learning about the impact of environmental chemicals on bone health. In contrast, other factors that may jeopardize pubertal bone accrual and peak bone mass acquisition have been studied extensively, with guidelines for management of the consequent poor skeletal health.

For PFAS, studies have reported deleterious effects on various body systems, such as the liver, immune system, thyroid, and the developing brain. The limited data related to bone suggest negative associations between certain, but not all, PFAS and bone density — ie, the higher the exposure, the worse the impact on bone health.

PFAS may affect health through alterations in the endocrine system. They have been associated with lower levels of testosterone and downregulation of its receptor (and testosterone is known to modulate bone formation and bone loss). On the other hand, some PFAS are estrogenic, which should be beneficial to bone. A direct impact of PFAS on pathways regulating activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) has also been postulated, with conflicting results.

Previous research on PFAS and human bone health has found mixed results. In adolescents, Xiong and colleagues  reported negative associations of PFOS, PFOA, and perfluorononanoic acid (PFNA), but not perfluorohexane sulfonic acid (PFHxS), levels with bone density at various sites, mostly in females. Carwile and associates  reported similar negative associations of blood concentrations of PFOA and PFOS and urinary concentrations of phthalates with bone density in adolescents, but only in males. Lin and coworkers also reported negative associations of PFOA and bone density in adult premenopausal women, but found no associations of PFOA and PFOS concentrations with self-reported fractures, suggesting questionable biological significance of these findings. These were all cross-sectional studies and did not report on the impact of these chemicals on longitudinal bone accrual.

In the recent study, Beglarian and colleagues examined the impact of PFAS on longitudinal changes in bone density in adolescents, drawn from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR) cohort and young adults from the Southern California Children’s Health Study (CHS) cohort. They found that in adolescents, higher baseline concentrations of PFOS predicted lower bone accrual over time. In young adults, there was a similar negative association of PFOS concentrations and bone density at baseline, but not with longitudinal bone accrual. In this study, other PFAS were not associated with bone outcomes.

Overall, research appears to suggest that PFOA, PFOS, and PFNA may have deleterious effects on bone density and bone accrual over time. However, data are not consistent across studies and across sexes, and more research is necessary to conclusively define the impact of these chemicals on skeletal health, particularly during the critical pubertal years of maximal bone accrual. In the meantime, continued efforts are necessary to reduce to concentrations of these PFAS in the environment.

Dr. Misra disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Bone health begins in childhood, particularly during the rapid bone accrual phase of puberty, which is essential for attaining optimal peak bone mass. Peak bone mass is achieved in early adult life and affects both immediate and future fracture risk. Genetic, nutritional, exercise-related, and hormonal factors, and certain diseases and medications, have deleterious effects on bone health.

In addition, emerging data suggest that certain manmade chemicals known as per- and polyfluoroalkyl substances (PFAS) may affect bone accrual during this important period and potentially increase the risk for osteoporosis in adulthood. Osteoporosis refers to increased fracture risk because of low bone density and affects a large proportion of postmenopausal women and older men.

New evidence comes from a recent study conducted by investigators from the Keck School of Medicine, who examined the impact of exposure to PFAS on skeletal outcomes in youth. Of note, participants were primarily Hispanic; this population has a higher risk for osteoporosis in adulthood. PFAS are manmade chemicals with water- and grease-resistant properties. They are used in a variety of products, such as nonstick cookware, food packaging, water-repellent clothing, stain-resistant fabrics, carpets, and in certain industrial processes. They are pervasive in the environment, in wildlife, and in humans.

Use and production of certain PFAS, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA),  have decreased over the past two decades, with a significant reduction in blood concentrations of these chemicals. However, they can be resistant to degradation and have very long half-lives. As a consequence, these «forever chemicals» continue to linger in the environment. Also, the risk for exposure to other PFAS persists, and almost every individual has detectable levels of PFAS in blood.

Scientists are still learning about the impact of environmental chemicals on bone health. In contrast, other factors that may jeopardize pubertal bone accrual and peak bone mass acquisition have been studied extensively, with guidelines for management of the consequent poor skeletal health.

For PFAS, studies have reported deleterious effects on various body systems, such as the liver, immune system, thyroid, and the developing brain. The limited data related to bone suggest negative associations between certain, but not all, PFAS and bone density — ie, the higher the exposure, the worse the impact on bone health.

PFAS may affect health through alterations in the endocrine system. They have been associated with lower levels of testosterone and downregulation of its receptor (and testosterone is known to modulate bone formation and bone loss). On the other hand, some PFAS are estrogenic, which should be beneficial to bone. A direct impact of PFAS on pathways regulating activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) has also been postulated, with conflicting results.

Previous research on PFAS and human bone health has found mixed results. In adolescents, Xiong and colleagues  reported negative associations of PFOS, PFOA, and perfluorononanoic acid (PFNA), but not perfluorohexane sulfonic acid (PFHxS), levels with bone density at various sites, mostly in females. Carwile and associates  reported similar negative associations of blood concentrations of PFOA and PFOS and urinary concentrations of phthalates with bone density in adolescents, but only in males. Lin and coworkers also reported negative associations of PFOA and bone density in adult premenopausal women, but found no associations of PFOA and PFOS concentrations with self-reported fractures, suggesting questionable biological significance of these findings. These were all cross-sectional studies and did not report on the impact of these chemicals on longitudinal bone accrual.

In the recent study, Beglarian and colleagues examined the impact of PFAS on longitudinal changes in bone density in adolescents, drawn from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR) cohort and young adults from the Southern California Children’s Health Study (CHS) cohort. They found that in adolescents, higher baseline concentrations of PFOS predicted lower bone accrual over time. In young adults, there was a similar negative association of PFOS concentrations and bone density at baseline, but not with longitudinal bone accrual. In this study, other PFAS were not associated with bone outcomes.

Overall, research appears to suggest that PFOA, PFOS, and PFNA may have deleterious effects on bone density and bone accrual over time. However, data are not consistent across studies and across sexes, and more research is necessary to conclusively define the impact of these chemicals on skeletal health, particularly during the critical pubertal years of maximal bone accrual. In the meantime, continued efforts are necessary to reduce to concentrations of these PFAS in the environment.

Dr. Misra disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Bone health begins in childhood, particularly during the rapid bone accrual phase of puberty, which is essential for attaining optimal peak bone mass. Peak bone mass is achieved in early adult life and affects both immediate and future fracture risk. Genetic, nutritional, exercise-related, and hormonal factors, and certain diseases and medications, have deleterious effects on bone health.

In addition, emerging data suggest that certain manmade chemicals known as per- and polyfluoroalkyl substances (PFAS) may affect bone accrual during this important period and potentially increase the risk for osteoporosis in adulthood. Osteoporosis refers to increased fracture risk because of low bone density and affects a large proportion of postmenopausal women and older men.

New evidence comes from a recent study conducted by investigators from the Keck School of Medicine, who examined the impact of exposure to PFAS on skeletal outcomes in youth. Of note, participants were primarily Hispanic; this population has a higher risk for osteoporosis in adulthood. PFAS are manmade chemicals with water- and grease-resistant properties. They are used in a variety of products, such as nonstick cookware, food packaging, water-repellent clothing, stain-resistant fabrics, carpets, and in certain industrial processes. They are pervasive in the environment, in wildlife, and in humans.

Use and production of certain PFAS, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA),  have decreased over the past two decades, with a significant reduction in blood concentrations of these chemicals. However, they can be resistant to degradation and have very long half-lives. As a consequence, these «forever chemicals» continue to linger in the environment. Also, the risk for exposure to other PFAS persists, and almost every individual has detectable levels of PFAS in blood.

Scientists are still learning about the impact of environmental chemicals on bone health. In contrast, other factors that may jeopardize pubertal bone accrual and peak bone mass acquisition have been studied extensively, with guidelines for management of the consequent poor skeletal health.

For PFAS, studies have reported deleterious effects on various body systems, such as the liver, immune system, thyroid, and the developing brain. The limited data related to bone suggest negative associations between certain, but not all, PFAS and bone density — ie, the higher the exposure, the worse the impact on bone health.

PFAS may affect health through alterations in the endocrine system. They have been associated with lower levels of testosterone and downregulation of its receptor (and testosterone is known to modulate bone formation and bone loss). On the other hand, some PFAS are estrogenic, which should be beneficial to bone. A direct impact of PFAS on pathways regulating activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) has also been postulated, with conflicting results.

Previous research on PFAS and human bone health has found mixed results. In adolescents, Xiong and colleagues  reported negative associations of PFOS, PFOA, and perfluorononanoic acid (PFNA), but not perfluorohexane sulfonic acid (PFHxS), levels with bone density at various sites, mostly in females. Carwile and associates  reported similar negative associations of blood concentrations of PFOA and PFOS and urinary concentrations of phthalates with bone density in adolescents, but only in males. Lin and coworkers also reported negative associations of PFOA and bone density in adult premenopausal women, but found no associations of PFOA and PFOS concentrations with self-reported fractures, suggesting questionable biological significance of these findings. These were all cross-sectional studies and did not report on the impact of these chemicals on longitudinal bone accrual.

In the recent study, Beglarian and colleagues examined the impact of PFAS on longitudinal changes in bone density in adolescents, drawn from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR) cohort and young adults from the Southern California Children’s Health Study (CHS) cohort. They found that in adolescents, higher baseline concentrations of PFOS predicted lower bone accrual over time. In young adults, there was a similar negative association of PFOS concentrations and bone density at baseline, but not with longitudinal bone accrual. In this study, other PFAS were not associated with bone outcomes.

Overall, research appears to suggest that PFOA, PFOS, and PFNA may have deleterious effects on bone density and bone accrual over time. However, data are not consistent across studies and across sexes, and more research is necessary to conclusively define the impact of these chemicals on skeletal health, particularly during the critical pubertal years of maximal bone accrual. In the meantime, continued efforts are necessary to reduce to concentrations of these PFAS in the environment.

Dr. Misra disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

A recently published prospective study in JAMA Network Open identified a significant association between children’s bone health and their proximity to green areas.

The literature emphasized the benefits of childhood exposure to green spaces for neurocognitive, social, behavioral, and mental development, as well as well-being. In addition, such exposure is linked to lower body mass index, increased physical activity, and reduced risks for overweight, obesity, and hypertension. However, specific data on bone mineral density implications are limited.

To address this gap, Hanne Sleurs, PhD, a researcher at the Universiteit Hasselt in Belgium, and colleagues followed the bone health of 327 participants from birth to 4-6 years and examined correlations with individuals’ exposure to green areas. Data collection occurred from October 2014 to July 2021.

Green spaces were categorized as high (vegetation height > 3 m), low (vegetation height ≤ 3 m), and mixed (combination of both). The distances of green spaces from participants’ residences ranged from a radius of 100 m to 3 km. Radial bone mineral density assessment was conducted using quantitative ultrasound during follow-up consultations.

The scientists found that participants frequently exposed to high and mixed vegetation areas within a 500-m radius of their homes had significantly higher bone mineral density than those at other distances or those frequenting spaces with different vegetation. In addition, access to larger green spaces with mixed and high vegetation within a 1-km radius was significantly associated with a lower likelihood of low bone density in children.

“These findings illustrate the positive impact on bone health of early childhood exposure to green areas near their homes during critical growth and development periods, with long-term implications,” wrote the researchers.

The results aligned with those of a prior study in which authors noted factors contributing to families’ frequent park visits, including shorter distances, safety, and park organization, as well as the natural diversity and activities offered.

One hypothesis explaining improved bone density in children visiting green areas was increased physical activity practiced in these locations. The mechanical load from exercise can activate signaling pathways favoring bone development. Literature also gathered data on the influence of green areas on young populations engaging in physical activities, showing positive outcomes.

According to the study authors, the findings are crucial for public health because they emphasize the need for urban investments in accessible green spaces as a strategy for fracture and osteoporosis prevention. In the long term, such initiatives translate to reduced public health expenses, along with physical and emotional gains in communities adopting environmental strategies, they concluded.

This article was translated from the Medscape Portuguese edition. A version of this article appeared on Medscape.com.

A recently published prospective study in JAMA Network Open identified a significant association between children’s bone health and their proximity to green areas.

The literature emphasized the benefits of childhood exposure to green spaces for neurocognitive, social, behavioral, and mental development, as well as well-being. In addition, such exposure is linked to lower body mass index, increased physical activity, and reduced risks for overweight, obesity, and hypertension. However, specific data on bone mineral density implications are limited.

To address this gap, Hanne Sleurs, PhD, a researcher at the Universiteit Hasselt in Belgium, and colleagues followed the bone health of 327 participants from birth to 4-6 years and examined correlations with individuals’ exposure to green areas. Data collection occurred from October 2014 to July 2021.

Green spaces were categorized as high (vegetation height > 3 m), low (vegetation height ≤ 3 m), and mixed (combination of both). The distances of green spaces from participants’ residences ranged from a radius of 100 m to 3 km. Radial bone mineral density assessment was conducted using quantitative ultrasound during follow-up consultations.

The scientists found that participants frequently exposed to high and mixed vegetation areas within a 500-m radius of their homes had significantly higher bone mineral density than those at other distances or those frequenting spaces with different vegetation. In addition, access to larger green spaces with mixed and high vegetation within a 1-km radius was significantly associated with a lower likelihood of low bone density in children.

“These findings illustrate the positive impact on bone health of early childhood exposure to green areas near their homes during critical growth and development periods, with long-term implications,” wrote the researchers.

The results aligned with those of a prior study in which authors noted factors contributing to families’ frequent park visits, including shorter distances, safety, and park organization, as well as the natural diversity and activities offered.

One hypothesis explaining improved bone density in children visiting green areas was increased physical activity practiced in these locations. The mechanical load from exercise can activate signaling pathways favoring bone development. Literature also gathered data on the influence of green areas on young populations engaging in physical activities, showing positive outcomes.

According to the study authors, the findings are crucial for public health because they emphasize the need for urban investments in accessible green spaces as a strategy for fracture and osteoporosis prevention. In the long term, such initiatives translate to reduced public health expenses, along with physical and emotional gains in communities adopting environmental strategies, they concluded.

This article was translated from the Medscape Portuguese edition. A version of this article appeared on Medscape.com.

A recently published prospective study in JAMA Network Open identified a significant association between children’s bone health and their proximity to green areas.

The literature emphasized the benefits of childhood exposure to green spaces for neurocognitive, social, behavioral, and mental development, as well as well-being. In addition, such exposure is linked to lower body mass index, increased physical activity, and reduced risks for overweight, obesity, and hypertension. However, specific data on bone mineral density implications are limited.

To address this gap, Hanne Sleurs, PhD, a researcher at the Universiteit Hasselt in Belgium, and colleagues followed the bone health of 327 participants from birth to 4-6 years and examined correlations with individuals’ exposure to green areas. Data collection occurred from October 2014 to July 2021.

Green spaces were categorized as high (vegetation height > 3 m), low (vegetation height ≤ 3 m), and mixed (combination of both). The distances of green spaces from participants’ residences ranged from a radius of 100 m to 3 km. Radial bone mineral density assessment was conducted using quantitative ultrasound during follow-up consultations.

The scientists found that participants frequently exposed to high and mixed vegetation areas within a 500-m radius of their homes had significantly higher bone mineral density than those at other distances or those frequenting spaces with different vegetation. In addition, access to larger green spaces with mixed and high vegetation within a 1-km radius was significantly associated with a lower likelihood of low bone density in children.

“These findings illustrate the positive impact on bone health of early childhood exposure to green areas near their homes during critical growth and development periods, with long-term implications,” wrote the researchers.

The results aligned with those of a prior study in which authors noted factors contributing to families’ frequent park visits, including shorter distances, safety, and park organization, as well as the natural diversity and activities offered.

One hypothesis explaining improved bone density in children visiting green areas was increased physical activity practiced in these locations. The mechanical load from exercise can activate signaling pathways favoring bone development. Literature also gathered data on the influence of green areas on young populations engaging in physical activities, showing positive outcomes.

According to the study authors, the findings are crucial for public health because they emphasize the need for urban investments in accessible green spaces as a strategy for fracture and osteoporosis prevention. In the long term, such initiatives translate to reduced public health expenses, along with physical and emotional gains in communities adopting environmental strategies, they concluded.

This article was translated from the Medscape Portuguese edition. A version of this article appeared on Medscape.com.

TOPLINE:

Intra-articular corticosteroid (IACS) injections pose a minimal risk of accelerating diabetes for most people, despite temporarily elevating blood glucose levels, according to a study published in Clinical Diabetes.

METHODOLOGY:

• Almost half of Americans with diabetes have arthritis, so glycemic control is a concern for many receiving IACS injections.
• IACS injections are known to cause short-term hyperglycemia, but their long-term effects on glycemic control are not well studied.
• For the retrospective cohort study, researchers at Mayo Clinic in Rochester, Minnesota, used electronic health records from 1169 adults who had received an IACS injection in one large joint between 2012 and 2018.
• They analyzed data on A1C levels for study participants from 18 months before and after the injections.
• Researchers assessed if participants had a greater-than-expected (defined as an increase of more than 0.5% above expected) concentration of A1C after the injection, and examined rates of diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome in the 30 days following an injection.

TAKEAWAY:

• Nearly 16% of people experienced a greater-than-expected A1C level after receiving an injection.
• A1C levels rose by an average of 1.2% in the greater-than-expected group, but decreased by an average of 0.2% in the average group.
• One patient had an episode of severe hyperglycemia that was linked to the injection.
• A baseline level of A1C above 8% was the only factor associated with a greater-than-expected increase in the marker after an IACS injection.

IN PRACTICE:

“Although most patients do not experience an increase in A1C after IACS, clinicians should counsel patients with suboptimally controlled diabetes about risks of further hyperglycemia after IACS administration,” the researchers wrote. 

SOURCE: 

The study was led by Terin T. Sytsma, MD, of Mayo Clinic in Rochester, Minnesota.

LIMITATIONS: 

The study was retrospective and could not establish causation. In addition, the population was of residents from one county in Minnesota, and was not racially or ethnically diverse. Details about the injection, such as location and total dose, were not available. The study also did not include a control group. 

DISCLOSURES:

The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences. The authors reported no relevant disclosures.

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

TOPLINE:

Intra-articular corticosteroid (IACS) injections pose a minimal risk of accelerating diabetes for most people, despite temporarily elevating blood glucose levels, according to a study published in Clinical Diabetes.

METHODOLOGY:

• Almost half of Americans with diabetes have arthritis, so glycemic control is a concern for many receiving IACS injections.
• IACS injections are known to cause short-term hyperglycemia, but their long-term effects on glycemic control are not well studied.
• For the retrospective cohort study, researchers at Mayo Clinic in Rochester, Minnesota, used electronic health records from 1169 adults who had received an IACS injection in one large joint between 2012 and 2018.
• They analyzed data on A1C levels for study participants from 18 months before and after the injections.
• Researchers assessed if participants had a greater-than-expected (defined as an increase of more than 0.5% above expected) concentration of A1C after the injection, and examined rates of diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome in the 30 days following an injection.

TAKEAWAY:

• Nearly 16% of people experienced a greater-than-expected A1C level after receiving an injection.
• A1C levels rose by an average of 1.2% in the greater-than-expected group, but decreased by an average of 0.2% in the average group.
• One patient had an episode of severe hyperglycemia that was linked to the injection.
• A baseline level of A1C above 8% was the only factor associated with a greater-than-expected increase in the marker after an IACS injection.

IN PRACTICE:

“Although most patients do not experience an increase in A1C after IACS, clinicians should counsel patients with suboptimally controlled diabetes about risks of further hyperglycemia after IACS administration,” the researchers wrote. 

SOURCE: 

The study was led by Terin T. Sytsma, MD, of Mayo Clinic in Rochester, Minnesota.

LIMITATIONS: 

The study was retrospective and could not establish causation. In addition, the population was of residents from one county in Minnesota, and was not racially or ethnically diverse. Details about the injection, such as location and total dose, were not available. The study also did not include a control group. 

DISCLOSURES:

The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences. The authors reported no relevant disclosures.

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

TOPLINE:

Intra-articular corticosteroid (IACS) injections pose a minimal risk of accelerating diabetes for most people, despite temporarily elevating blood glucose levels, according to a study published in Clinical Diabetes.

METHODOLOGY:

• Almost half of Americans with diabetes have arthritis, so glycemic control is a concern for many receiving IACS injections.
• IACS injections are known to cause short-term hyperglycemia, but their long-term effects on glycemic control are not well studied.
• For the retrospective cohort study, researchers at Mayo Clinic in Rochester, Minnesota, used electronic health records from 1169 adults who had received an IACS injection in one large joint between 2012 and 2018.
• They analyzed data on A1C levels for study participants from 18 months before and after the injections.
• Researchers assessed if participants had a greater-than-expected (defined as an increase of more than 0.5% above expected) concentration of A1C after the injection, and examined rates of diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome in the 30 days following an injection.

TAKEAWAY:

• Nearly 16% of people experienced a greater-than-expected A1C level after receiving an injection.
• A1C levels rose by an average of 1.2% in the greater-than-expected group, but decreased by an average of 0.2% in the average group.
• One patient had an episode of severe hyperglycemia that was linked to the injection.
• A baseline level of A1C above 8% was the only factor associated with a greater-than-expected increase in the marker after an IACS injection.

IN PRACTICE:

“Although most patients do not experience an increase in A1C after IACS, clinicians should counsel patients with suboptimally controlled diabetes about risks of further hyperglycemia after IACS administration,” the researchers wrote. 

SOURCE: 

The study was led by Terin T. Sytsma, MD, of Mayo Clinic in Rochester, Minnesota.

LIMITATIONS: 

The study was retrospective and could not establish causation. In addition, the population was of residents from one county in Minnesota, and was not racially or ethnically diverse. Details about the injection, such as location and total dose, were not available. The study also did not include a control group. 

DISCLOSURES:

The study was funded by Mayo Clinic and the National Center for Advancing Translational Sciences. The authors reported no relevant disclosures.

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

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Pediatric rheumatologists are calling a “Code (p)RED” — a pediatric rheumatology educational deficit.

There are too few pediatric rheumatologists to meet patient demand in the United States, and projections suggest that gap will continue to widen. Disappointing match trends also reflect issues with recruitment: Since 2019, only 50%-75% of pediatric rheumatology fellowship positions have been filled each year. For 2024, the subspecialty filled 32 of 52 positions.

University of Minnesota

Lack of exposure during medical school and residency, financial concerns, and a lengthy, research-focused fellowship are seen as major contributors to the workforce shortage, and novel solutions are needed to close the gap, experts argued in a recent presentation at the annual meeting of the American College of Rheumatology.

“It’s so important now to get ahead of this because what I’m afraid of is in 10-20 years, we’re not going to have a field,” Colleen Correll, MD, MPH, an associate professor in the division of pediatric rheumatology at the University of Minnesota Medical School in Minneapolis, told this news organization.
 

Growing Demand, Falling Supply

Because the subspecialty was officially recognized by the American Board of Pediatrics in 1991, “it’s always been a small group of providers,” Dr. Correll said. “It’s honestly always been a recognized issue in our field.”

But a 2022 report by the ACR on the pediatric workforce has brought more attention to the issue. Dr. Correll led the study and is the chair of ACR›s Pediatric Rheumatology Committee. According to the report, an estimated 287 pediatric rheumatologists were working as full-time clinicians in 2015, while the estimated demand was 382 providers. By 2030, this projected supply of pediatric rheumatologists fell to 261, while demand rose to 461 full-time providers.

The distribution of pediatric rheumatologists is also an issue. It’s generally thought that there should be at least one pediatric rheumatologist per 100,000 children, Dr. Correll explained. According to ACR estimates, the northeast region had approximately 0.83 pediatric rheumatologists per 100,000 in 2015, while the south central and southwest regions had 0.17 and 0.20 providers per 100,000 children, respectively. Projected estimates for 2030 dipped to 0.04 or lower for the south central, southwest, and southeast regions.

A separate study from the American Board of Pediatrics, also led by Dr. Correll, that is still under review offered more optimistic projections, suggesting that there would be a 75% increase in pediatric rheumatologists from 0.27 per 100,000 children in 2020 to 0.47 per 100,000 children in 2040.

“This does look better than the ACR study, though 0.47 is still a really small number and an inadequate number to treat our children in need,” she said during her presentation at the annual meeting of the American College of Rheumatology.
 

Lack of Exposure During Medical Education

Few medical schools have pediatric rheumatology built into their curriculum, whether that is a whole course or a single lecture, said Jay Mehta, MD, who directs the pediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. Dr. Mehta, for example, did not know that pediatric rheumatology was a field before entering residency, he said. But residencies can also lack exposure: An estimated one third of residencies do not have a single pediatric rheumatologist on staff, he said.

Children&#039;s Hospital of Philadelphia

“Those are places where people aren’t necessarily getting exposure to pediatric rheumatology,” he told this news organization, “and we know that if you’re not exposed to a field, it’s very, very unlikely that you will go into that field.”

The ACR’s Pediatric Rheumatology Residency Program is one way that the organization is working to address this issue. The program sends pediatric residents with an interest in rheumatology to the ACR annual meeting. The Rheumatology Research Foundation also runs a visiting professorship program, where a pediatric rheumatologist conducts a rheumatology education forum at an institution with no pediatric rheumatology program.

“I’ve done it a couple of times,” Dr. Mehta said during his presentation at the annual meeting. “It’s one of the most rewarding things I’ve done.”
 

Financial Concerns

Additionally, although pediatric rheumatology requires more training, these subspecialists will likely make less than their general pediatric colleagues over their career. According to one study in Pediatrics, a pediatric resident pursuing rheumatology is projected to make $1.2 million dollars less over the course of their career compared with someone who started their career in general pediatrics immediately after residency. (Negative financial returns were also found for all pediatric subspecialities except for cardiology, critical care, and neonatology.)

This lower earning potential is likely a deterrent, especially for those with educational debt. In one analysis published in October, medical students with at least $200,000 in education debt were 43% more likely to go into higher-paying pediatric subspecialities than those with no debt. Nearly three out of four medical graduates have education debt, according to the American Association of Medical Colleges, with a median debt of $200,000.

While the Pediatric Specialty Loan Repayment Program was specifically designed to aid pediatric subspecialists with their educational debt, qualifying for the program is difficult for pediatric rheumatologists, explained Kristen N. Hayward, MD, of Seattle Children’s in Washington. The program provides up to $100,000 in loan forgiveness in exchange for 3 years of practicing in an underserved area; however, the program stipulates that providers must provide full-time (40 hours per week) clinical care. At academic institutions, where most pediatric rheumatologists practice, there is usually a research component to their position, and even if a provider works the equivalent of 40 hours per week in a clinic in addition to their research, they don’t qualify for the program, Dr. Hayward said.

“It’s very difficult to find someone who’s actually only doing clinical work,” she said.

The ACR has worked to combat some of these economic constraints by demonstrating the direct and downstream value of rheumatologic care, Dr. Hayward said. In a recent white paper, it was estimated that including office visits, consultations, lab testing, and radiology services, one full-time equivalent rheumatologist generates $3.5 million in revenue every year and saves health systems more than $2700 per patient per year.

In addition to placing greater value on rheumatologic care, the healthcare system also needs to recognize the current nonbillable hours that pediatric rheumatologists spend taking care of patients, Dr. Hayward noted.

Especially with electronic medical records (EMRs) and online communication with patients, “there is increasingly a lot of patient care that happens outside of clinic and that takes a lot of time,” Dr. Hayward said. For example, she spends between 1 and 2 hours every day in the EMR refilling medications and responding to patient concerns, and “that all is done in my spare time,” she said. “That’s not billed to the patient in anyway.”
 

Length of Fellowship

The pediatric rheumatology fellowship is a 3-year program — like other pediatric subspecialities — with a research requirement. By comparison, adult rheumatology fellowships are 2 years, and fellows can pursue additional research training if they have a strong interest.

“It sounds like just 1 more year, but I think it’s coming at a really pivotal point in people’s lives, and that 1 year can make a huge difference,” Dr. Hayward explained.

The 2 years of research might also be a deterrent for individuals who know they are only interested in clinical work, she added. About half of pediatric subspecialists only pursue clinical work after graduation, according to a recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) focused on the future pediatric physician workforce.

Additionally, only 17% of pediatric rheumatologists spend more than half of their time in research, said Fred Rivara, MD, MPH, chair of the NASEM report, in a statement included in Dr. Hayward’s ACR presentation. The report, which recommended strategies to bolster the pediatric workforce, argued that the American Board of Pediatrics should develop alternative training pathways, including 2-year, clinically heavy fellowships.

The ACR workforce team is also exploring alternative training models like competency-based education, Dr. Hayward said. The Education in Pediatrics Across the Continuum project is already using this approach from medical school to pediatric residency. While this type of outcome-based program has not been tried at the fellowship level, «this has been done, it could be done, and I think we could learn from our colleagues about how they have done this successfully,» she noted.

Ultimately, Dr. Hayward emphasized that there needs to be a “sea change” to close the workforce gap — with multiple interventions addressing these individual challenges.

“Unless we all pitch in and find one way that we can all move this issue forward, we are going to be drowning in a sea of Epic inbox messages,” she said, “and never get to see the patients we want to see.”

Dr. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer. Dr. Correll and Dr. Mehta had no relevant disclosures.

A version of this article appeared on Medscape.com.

Pediatric rheumatologists are calling a “Code (p)RED” — a pediatric rheumatology educational deficit.

There are too few pediatric rheumatologists to meet patient demand in the United States, and projections suggest that gap will continue to widen. Disappointing match trends also reflect issues with recruitment: Since 2019, only 50%-75% of pediatric rheumatology fellowship positions have been filled each year. For 2024, the subspecialty filled 32 of 52 positions.

University of Minnesota

Lack of exposure during medical school and residency, financial concerns, and a lengthy, research-focused fellowship are seen as major contributors to the workforce shortage, and novel solutions are needed to close the gap, experts argued in a recent presentation at the annual meeting of the American College of Rheumatology.

“It’s so important now to get ahead of this because what I’m afraid of is in 10-20 years, we’re not going to have a field,” Colleen Correll, MD, MPH, an associate professor in the division of pediatric rheumatology at the University of Minnesota Medical School in Minneapolis, told this news organization.
 

Growing Demand, Falling Supply

Because the subspecialty was officially recognized by the American Board of Pediatrics in 1991, “it’s always been a small group of providers,” Dr. Correll said. “It’s honestly always been a recognized issue in our field.”

But a 2022 report by the ACR on the pediatric workforce has brought more attention to the issue. Dr. Correll led the study and is the chair of ACR›s Pediatric Rheumatology Committee. According to the report, an estimated 287 pediatric rheumatologists were working as full-time clinicians in 2015, while the estimated demand was 382 providers. By 2030, this projected supply of pediatric rheumatologists fell to 261, while demand rose to 461 full-time providers.

The distribution of pediatric rheumatologists is also an issue. It’s generally thought that there should be at least one pediatric rheumatologist per 100,000 children, Dr. Correll explained. According to ACR estimates, the northeast region had approximately 0.83 pediatric rheumatologists per 100,000 in 2015, while the south central and southwest regions had 0.17 and 0.20 providers per 100,000 children, respectively. Projected estimates for 2030 dipped to 0.04 or lower for the south central, southwest, and southeast regions.

A separate study from the American Board of Pediatrics, also led by Dr. Correll, that is still under review offered more optimistic projections, suggesting that there would be a 75% increase in pediatric rheumatologists from 0.27 per 100,000 children in 2020 to 0.47 per 100,000 children in 2040.

“This does look better than the ACR study, though 0.47 is still a really small number and an inadequate number to treat our children in need,” she said during her presentation at the annual meeting of the American College of Rheumatology.
 

Lack of Exposure During Medical Education

Few medical schools have pediatric rheumatology built into their curriculum, whether that is a whole course or a single lecture, said Jay Mehta, MD, who directs the pediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. Dr. Mehta, for example, did not know that pediatric rheumatology was a field before entering residency, he said. But residencies can also lack exposure: An estimated one third of residencies do not have a single pediatric rheumatologist on staff, he said.

Children&#039;s Hospital of Philadelphia

“Those are places where people aren’t necessarily getting exposure to pediatric rheumatology,” he told this news organization, “and we know that if you’re not exposed to a field, it’s very, very unlikely that you will go into that field.”

The ACR’s Pediatric Rheumatology Residency Program is one way that the organization is working to address this issue. The program sends pediatric residents with an interest in rheumatology to the ACR annual meeting. The Rheumatology Research Foundation also runs a visiting professorship program, where a pediatric rheumatologist conducts a rheumatology education forum at an institution with no pediatric rheumatology program.

“I’ve done it a couple of times,” Dr. Mehta said during his presentation at the annual meeting. “It’s one of the most rewarding things I’ve done.”
 

Financial Concerns

Additionally, although pediatric rheumatology requires more training, these subspecialists will likely make less than their general pediatric colleagues over their career. According to one study in Pediatrics, a pediatric resident pursuing rheumatology is projected to make $1.2 million dollars less over the course of their career compared with someone who started their career in general pediatrics immediately after residency. (Negative financial returns were also found for all pediatric subspecialities except for cardiology, critical care, and neonatology.)

This lower earning potential is likely a deterrent, especially for those with educational debt. In one analysis published in October, medical students with at least $200,000 in education debt were 43% more likely to go into higher-paying pediatric subspecialities than those with no debt. Nearly three out of four medical graduates have education debt, according to the American Association of Medical Colleges, with a median debt of $200,000.

While the Pediatric Specialty Loan Repayment Program was specifically designed to aid pediatric subspecialists with their educational debt, qualifying for the program is difficult for pediatric rheumatologists, explained Kristen N. Hayward, MD, of Seattle Children’s in Washington. The program provides up to $100,000 in loan forgiveness in exchange for 3 years of practicing in an underserved area; however, the program stipulates that providers must provide full-time (40 hours per week) clinical care. At academic institutions, where most pediatric rheumatologists practice, there is usually a research component to their position, and even if a provider works the equivalent of 40 hours per week in a clinic in addition to their research, they don’t qualify for the program, Dr. Hayward said.

“It’s very difficult to find someone who’s actually only doing clinical work,” she said.

The ACR has worked to combat some of these economic constraints by demonstrating the direct and downstream value of rheumatologic care, Dr. Hayward said. In a recent white paper, it was estimated that including office visits, consultations, lab testing, and radiology services, one full-time equivalent rheumatologist generates $3.5 million in revenue every year and saves health systems more than $2700 per patient per year.

In addition to placing greater value on rheumatologic care, the healthcare system also needs to recognize the current nonbillable hours that pediatric rheumatologists spend taking care of patients, Dr. Hayward noted.

Especially with electronic medical records (EMRs) and online communication with patients, “there is increasingly a lot of patient care that happens outside of clinic and that takes a lot of time,” Dr. Hayward said. For example, she spends between 1 and 2 hours every day in the EMR refilling medications and responding to patient concerns, and “that all is done in my spare time,” she said. “That’s not billed to the patient in anyway.”
 

Length of Fellowship

The pediatric rheumatology fellowship is a 3-year program — like other pediatric subspecialities — with a research requirement. By comparison, adult rheumatology fellowships are 2 years, and fellows can pursue additional research training if they have a strong interest.

“It sounds like just 1 more year, but I think it’s coming at a really pivotal point in people’s lives, and that 1 year can make a huge difference,” Dr. Hayward explained.

The 2 years of research might also be a deterrent for individuals who know they are only interested in clinical work, she added. About half of pediatric subspecialists only pursue clinical work after graduation, according to a recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) focused on the future pediatric physician workforce.

Additionally, only 17% of pediatric rheumatologists spend more than half of their time in research, said Fred Rivara, MD, MPH, chair of the NASEM report, in a statement included in Dr. Hayward’s ACR presentation. The report, which recommended strategies to bolster the pediatric workforce, argued that the American Board of Pediatrics should develop alternative training pathways, including 2-year, clinically heavy fellowships.

The ACR workforce team is also exploring alternative training models like competency-based education, Dr. Hayward said. The Education in Pediatrics Across the Continuum project is already using this approach from medical school to pediatric residency. While this type of outcome-based program has not been tried at the fellowship level, «this has been done, it could be done, and I think we could learn from our colleagues about how they have done this successfully,» she noted.

Ultimately, Dr. Hayward emphasized that there needs to be a “sea change” to close the workforce gap — with multiple interventions addressing these individual challenges.

“Unless we all pitch in and find one way that we can all move this issue forward, we are going to be drowning in a sea of Epic inbox messages,” she said, “and never get to see the patients we want to see.”

Dr. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer. Dr. Correll and Dr. Mehta had no relevant disclosures.

A version of this article appeared on Medscape.com.

Pediatric rheumatologists are calling a “Code (p)RED” — a pediatric rheumatology educational deficit.

There are too few pediatric rheumatologists to meet patient demand in the United States, and projections suggest that gap will continue to widen. Disappointing match trends also reflect issues with recruitment: Since 2019, only 50%-75% of pediatric rheumatology fellowship positions have been filled each year. For 2024, the subspecialty filled 32 of 52 positions.

University of Minnesota

Lack of exposure during medical school and residency, financial concerns, and a lengthy, research-focused fellowship are seen as major contributors to the workforce shortage, and novel solutions are needed to close the gap, experts argued in a recent presentation at the annual meeting of the American College of Rheumatology.

“It’s so important now to get ahead of this because what I’m afraid of is in 10-20 years, we’re not going to have a field,” Colleen Correll, MD, MPH, an associate professor in the division of pediatric rheumatology at the University of Minnesota Medical School in Minneapolis, told this news organization.
 

Growing Demand, Falling Supply

Because the subspecialty was officially recognized by the American Board of Pediatrics in 1991, “it’s always been a small group of providers,” Dr. Correll said. “It’s honestly always been a recognized issue in our field.”

But a 2022 report by the ACR on the pediatric workforce has brought more attention to the issue. Dr. Correll led the study and is the chair of ACR›s Pediatric Rheumatology Committee. According to the report, an estimated 287 pediatric rheumatologists were working as full-time clinicians in 2015, while the estimated demand was 382 providers. By 2030, this projected supply of pediatric rheumatologists fell to 261, while demand rose to 461 full-time providers.

The distribution of pediatric rheumatologists is also an issue. It’s generally thought that there should be at least one pediatric rheumatologist per 100,000 children, Dr. Correll explained. According to ACR estimates, the northeast region had approximately 0.83 pediatric rheumatologists per 100,000 in 2015, while the south central and southwest regions had 0.17 and 0.20 providers per 100,000 children, respectively. Projected estimates for 2030 dipped to 0.04 or lower for the south central, southwest, and southeast regions.

A separate study from the American Board of Pediatrics, also led by Dr. Correll, that is still under review offered more optimistic projections, suggesting that there would be a 75% increase in pediatric rheumatologists from 0.27 per 100,000 children in 2020 to 0.47 per 100,000 children in 2040.

“This does look better than the ACR study, though 0.47 is still a really small number and an inadequate number to treat our children in need,” she said during her presentation at the annual meeting of the American College of Rheumatology.
 

Lack of Exposure During Medical Education

Few medical schools have pediatric rheumatology built into their curriculum, whether that is a whole course or a single lecture, said Jay Mehta, MD, who directs the pediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. Dr. Mehta, for example, did not know that pediatric rheumatology was a field before entering residency, he said. But residencies can also lack exposure: An estimated one third of residencies do not have a single pediatric rheumatologist on staff, he said.

Children&#039;s Hospital of Philadelphia

“Those are places where people aren’t necessarily getting exposure to pediatric rheumatology,” he told this news organization, “and we know that if you’re not exposed to a field, it’s very, very unlikely that you will go into that field.”

The ACR’s Pediatric Rheumatology Residency Program is one way that the organization is working to address this issue. The program sends pediatric residents with an interest in rheumatology to the ACR annual meeting. The Rheumatology Research Foundation also runs a visiting professorship program, where a pediatric rheumatologist conducts a rheumatology education forum at an institution with no pediatric rheumatology program.

“I’ve done it a couple of times,” Dr. Mehta said during his presentation at the annual meeting. “It’s one of the most rewarding things I’ve done.”
 

Financial Concerns

Additionally, although pediatric rheumatology requires more training, these subspecialists will likely make less than their general pediatric colleagues over their career. According to one study in Pediatrics, a pediatric resident pursuing rheumatology is projected to make $1.2 million dollars less over the course of their career compared with someone who started their career in general pediatrics immediately after residency. (Negative financial returns were also found for all pediatric subspecialities except for cardiology, critical care, and neonatology.)

This lower earning potential is likely a deterrent, especially for those with educational debt. In one analysis published in October, medical students with at least $200,000 in education debt were 43% more likely to go into higher-paying pediatric subspecialities than those with no debt. Nearly three out of four medical graduates have education debt, according to the American Association of Medical Colleges, with a median debt of $200,000.

While the Pediatric Specialty Loan Repayment Program was specifically designed to aid pediatric subspecialists with their educational debt, qualifying for the program is difficult for pediatric rheumatologists, explained Kristen N. Hayward, MD, of Seattle Children’s in Washington. The program provides up to $100,000 in loan forgiveness in exchange for 3 years of practicing in an underserved area; however, the program stipulates that providers must provide full-time (40 hours per week) clinical care. At academic institutions, where most pediatric rheumatologists practice, there is usually a research component to their position, and even if a provider works the equivalent of 40 hours per week in a clinic in addition to their research, they don’t qualify for the program, Dr. Hayward said.

“It’s very difficult to find someone who’s actually only doing clinical work,” she said.

The ACR has worked to combat some of these economic constraints by demonstrating the direct and downstream value of rheumatologic care, Dr. Hayward said. In a recent white paper, it was estimated that including office visits, consultations, lab testing, and radiology services, one full-time equivalent rheumatologist generates $3.5 million in revenue every year and saves health systems more than $2700 per patient per year.

In addition to placing greater value on rheumatologic care, the healthcare system also needs to recognize the current nonbillable hours that pediatric rheumatologists spend taking care of patients, Dr. Hayward noted.

Especially with electronic medical records (EMRs) and online communication with patients, “there is increasingly a lot of patient care that happens outside of clinic and that takes a lot of time,” Dr. Hayward said. For example, she spends between 1 and 2 hours every day in the EMR refilling medications and responding to patient concerns, and “that all is done in my spare time,” she said. “That’s not billed to the patient in anyway.”
 

Length of Fellowship

The pediatric rheumatology fellowship is a 3-year program — like other pediatric subspecialities — with a research requirement. By comparison, adult rheumatology fellowships are 2 years, and fellows can pursue additional research training if they have a strong interest.

“It sounds like just 1 more year, but I think it’s coming at a really pivotal point in people’s lives, and that 1 year can make a huge difference,” Dr. Hayward explained.

The 2 years of research might also be a deterrent for individuals who know they are only interested in clinical work, she added. About half of pediatric subspecialists only pursue clinical work after graduation, according to a recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) focused on the future pediatric physician workforce.

Additionally, only 17% of pediatric rheumatologists spend more than half of their time in research, said Fred Rivara, MD, MPH, chair of the NASEM report, in a statement included in Dr. Hayward’s ACR presentation. The report, which recommended strategies to bolster the pediatric workforce, argued that the American Board of Pediatrics should develop alternative training pathways, including 2-year, clinically heavy fellowships.

The ACR workforce team is also exploring alternative training models like competency-based education, Dr. Hayward said. The Education in Pediatrics Across the Continuum project is already using this approach from medical school to pediatric residency. While this type of outcome-based program has not been tried at the fellowship level, «this has been done, it could be done, and I think we could learn from our colleagues about how they have done this successfully,» she noted.

Ultimately, Dr. Hayward emphasized that there needs to be a “sea change” to close the workforce gap — with multiple interventions addressing these individual challenges.

“Unless we all pitch in and find one way that we can all move this issue forward, we are going to be drowning in a sea of Epic inbox messages,” she said, “and never get to see the patients we want to see.”

Dr. Hayward previously owned stock/stock options for AbbVie/Abbott, Cigna/Express Scripts, Merck, and Teva and has received an educational grant from Pfizer. Dr. Correll and Dr. Mehta had no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Only half of teens and young adults on teratogenic medication report being asked about sexual activity by their rheumatologist, and 38% did not know that their medication would be harmful to a fetus, according to a new survey.

While pediatric rheumatology providers may think that health screenings and contraceptive counseling are happening elsewhere, “this study suggests that a lot of patients are being missed, including those on teratogens,” noted Brittany M. Huynh, MD, MPH, a pediatric rheumatology fellow at the Indiana University School of Medicine in Indianapolis. She led the study and presented the findings at the American College of Rheumatology annual meeting.

Indiana University

For the study, Dr. Huynh and colleagues recruited patients aged 14-23 years who were assigned female at birth and were followed at pediatric rheumatology clinics affiliated with Indiana University. Participants completed a one-time survey between October 2020 and July 2022 and were asked about their sexual reproductive health experience and knowledge. Notably, all but four surveys were completed prior to the US Supreme Court Dobbs decision overturning Roe v. Wade.

Of responses from 108 participants, the most common diagnoses were juvenile idiopathic arthritis (52%) and systemic lupus erythematosus (16%). About one third (36%) of patients were on teratogenic medication, with the most common being methotrexate. About three fourths (76%) were White, and the average age of respondents was 16.7.

Most participants (82%) said they had been asked about sexual activity by a health care provider, but only 38% said their pediatric rheumatologist discussed this topic with them. Of the 39 patients on teratogenic medication, 54% said they had been asked about sexual activity by their pediatric rheumatologist, and only 51% said they had received teratogenicity counseling.

A larger percentage (85%) of this group reported receiving sexual activity screenings by any provider, but there was little difference in counseling about teratogenic medication.

This suggests that this type of risk counseling “is almost exclusively done by (pediatric rheumatologists), if at all,” Dr. Huynh noted during her presentation.

In total, 56% of all patients said a provider had talked to them about how to prevent pregnancy, and 20% said they had been counseled about how to get and use emergency contraception. Only 6% of patients said their pediatric rheumatologist had discussed emergency contraception during appointments.

Although sexual activity screenings were associated with current teratogen use, pregnancy prevention counseling and emergency contraceptive counseling were not associated with teratogen use or reported sexual activity.

The survey also revealed that there were gaps in knowledge about the health effects of rheumatic medication. Of the patients on teratogens, 38% did not know that their medication could harm a fetus if they became pregnant. Only 9% of patients not on teratogens correctly answered that their medication would not harm a fetus.

Previous studies have also shown that rheumatology patients do not know that their medications can be teratogenic, noted Cuoghi Edens, MD, a rheumatologist at the University of Chicago, who sees both adult and pediatric patients. She was not involved with the study. The larger challenge is how to best educate patients, she said.

While hopefully a patient’s primary care provider is discussing these issues with them, these patients often see their rheumatologist more frequently and more consistently than other providers, Dr. Edens said.

UChicago Medicine

“We are sometimes the continuity of care for the patient versus their primary care, even though it should be a group effort of trying to some of these questions,” she said.

Conducting reproductive health screenings in pediatric rheumatology clinics can be difficult though, Dr. Edens noted, not only because of time constraints but also because parents often attend appointments with their child and likely have been for years. These screenings are most accurate when done one-on-one, so pivoting and removing the parents from the room can be awkward for providers, Dr. Edens said.

She advised that starting these conversations early on can be one way to ease into talking about reproductive health. In her own practice, Dr. Huynh sets aside time during appointments to speak with adolescent patients privately.

“We always discuss teratogenic medication. I always talk to them about the fact that I’m going to be doing pregnancy testing with their other screening labs because of the risks associated,” she said. “I also specifically set time aside for patients on teratogens to talk about emergency contraception and offer a prescription, if they’re interested.”

Dr. Huynh emphasized that providing easy access to emergency contraception is key. The ACR reproductive health guidelines — although geared toward adults — recommend discussing emergency contraception with patients, and Dr. Huynh advocates writing prescriptions for interested patients.

“They can fill it and have it easily accessible, so that there are no additional barriers, particularly for people who have these higher risks,” she said.

While emergency contraceptives are also available over the counter, it can be awkward for young people to ask for them, she said, and they can be expensive if not covered under insurance. Providing a prescription is one way to avoid those issues, Dr. Huynh said.

“Certainly, you have to have some parent buy-in, because if there is going to be a script, it’s probably going to be under insurance,” she said. “But in my experience, parents are happy to have it around as long as you’re talking it through with them as well as the young person.”

Dr. Huynh and Dr. Edens had no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Only half of teens and young adults on teratogenic medication report being asked about sexual activity by their rheumatologist, and 38% did not know that their medication would be harmful to a fetus, according to a new survey.

While pediatric rheumatology providers may think that health screenings and contraceptive counseling are happening elsewhere, “this study suggests that a lot of patients are being missed, including those on teratogens,” noted Brittany M. Huynh, MD, MPH, a pediatric rheumatology fellow at the Indiana University School of Medicine in Indianapolis. She led the study and presented the findings at the American College of Rheumatology annual meeting.

Indiana University

For the study, Dr. Huynh and colleagues recruited patients aged 14-23 years who were assigned female at birth and were followed at pediatric rheumatology clinics affiliated with Indiana University. Participants completed a one-time survey between October 2020 and July 2022 and were asked about their sexual reproductive health experience and knowledge. Notably, all but four surveys were completed prior to the US Supreme Court Dobbs decision overturning Roe v. Wade.

Of responses from 108 participants, the most common diagnoses were juvenile idiopathic arthritis (52%) and systemic lupus erythematosus (16%). About one third (36%) of patients were on teratogenic medication, with the most common being methotrexate. About three fourths (76%) were White, and the average age of respondents was 16.7.

Most participants (82%) said they had been asked about sexual activity by a health care provider, but only 38% said their pediatric rheumatologist discussed this topic with them. Of the 39 patients on teratogenic medication, 54% said they had been asked about sexual activity by their pediatric rheumatologist, and only 51% said they had received teratogenicity counseling.

A larger percentage (85%) of this group reported receiving sexual activity screenings by any provider, but there was little difference in counseling about teratogenic medication.

This suggests that this type of risk counseling “is almost exclusively done by (pediatric rheumatologists), if at all,” Dr. Huynh noted during her presentation.

In total, 56% of all patients said a provider had talked to them about how to prevent pregnancy, and 20% said they had been counseled about how to get and use emergency contraception. Only 6% of patients said their pediatric rheumatologist had discussed emergency contraception during appointments.

Although sexual activity screenings were associated with current teratogen use, pregnancy prevention counseling and emergency contraceptive counseling were not associated with teratogen use or reported sexual activity.

The survey also revealed that there were gaps in knowledge about the health effects of rheumatic medication. Of the patients on teratogens, 38% did not know that their medication could harm a fetus if they became pregnant. Only 9% of patients not on teratogens correctly answered that their medication would not harm a fetus.

Previous studies have also shown that rheumatology patients do not know that their medications can be teratogenic, noted Cuoghi Edens, MD, a rheumatologist at the University of Chicago, who sees both adult and pediatric patients. She was not involved with the study. The larger challenge is how to best educate patients, she said.

While hopefully a patient’s primary care provider is discussing these issues with them, these patients often see their rheumatologist more frequently and more consistently than other providers, Dr. Edens said.

UChicago Medicine

“We are sometimes the continuity of care for the patient versus their primary care, even though it should be a group effort of trying to some of these questions,” she said.

Conducting reproductive health screenings in pediatric rheumatology clinics can be difficult though, Dr. Edens noted, not only because of time constraints but also because parents often attend appointments with their child and likely have been for years. These screenings are most accurate when done one-on-one, so pivoting and removing the parents from the room can be awkward for providers, Dr. Edens said.

She advised that starting these conversations early on can be one way to ease into talking about reproductive health. In her own practice, Dr. Huynh sets aside time during appointments to speak with adolescent patients privately.

“We always discuss teratogenic medication. I always talk to them about the fact that I’m going to be doing pregnancy testing with their other screening labs because of the risks associated,” she said. “I also specifically set time aside for patients on teratogens to talk about emergency contraception and offer a prescription, if they’re interested.”

Dr. Huynh emphasized that providing easy access to emergency contraception is key. The ACR reproductive health guidelines — although geared toward adults — recommend discussing emergency contraception with patients, and Dr. Huynh advocates writing prescriptions for interested patients.

“They can fill it and have it easily accessible, so that there are no additional barriers, particularly for people who have these higher risks,” she said.

While emergency contraceptives are also available over the counter, it can be awkward for young people to ask for them, she said, and they can be expensive if not covered under insurance. Providing a prescription is one way to avoid those issues, Dr. Huynh said.

“Certainly, you have to have some parent buy-in, because if there is going to be a script, it’s probably going to be under insurance,” she said. “But in my experience, parents are happy to have it around as long as you’re talking it through with them as well as the young person.”

Dr. Huynh and Dr. Edens had no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Only half of teens and young adults on teratogenic medication report being asked about sexual activity by their rheumatologist, and 38% did not know that their medication would be harmful to a fetus, according to a new survey.

While pediatric rheumatology providers may think that health screenings and contraceptive counseling are happening elsewhere, “this study suggests that a lot of patients are being missed, including those on teratogens,” noted Brittany M. Huynh, MD, MPH, a pediatric rheumatology fellow at the Indiana University School of Medicine in Indianapolis. She led the study and presented the findings at the American College of Rheumatology annual meeting.

Indiana University

For the study, Dr. Huynh and colleagues recruited patients aged 14-23 years who were assigned female at birth and were followed at pediatric rheumatology clinics affiliated with Indiana University. Participants completed a one-time survey between October 2020 and July 2022 and were asked about their sexual reproductive health experience and knowledge. Notably, all but four surveys were completed prior to the US Supreme Court Dobbs decision overturning Roe v. Wade.

Of responses from 108 participants, the most common diagnoses were juvenile idiopathic arthritis (52%) and systemic lupus erythematosus (16%). About one third (36%) of patients were on teratogenic medication, with the most common being methotrexate. About three fourths (76%) were White, and the average age of respondents was 16.7.

Most participants (82%) said they had been asked about sexual activity by a health care provider, but only 38% said their pediatric rheumatologist discussed this topic with them. Of the 39 patients on teratogenic medication, 54% said they had been asked about sexual activity by their pediatric rheumatologist, and only 51% said they had received teratogenicity counseling.

A larger percentage (85%) of this group reported receiving sexual activity screenings by any provider, but there was little difference in counseling about teratogenic medication.

This suggests that this type of risk counseling “is almost exclusively done by (pediatric rheumatologists), if at all,” Dr. Huynh noted during her presentation.

In total, 56% of all patients said a provider had talked to them about how to prevent pregnancy, and 20% said they had been counseled about how to get and use emergency contraception. Only 6% of patients said their pediatric rheumatologist had discussed emergency contraception during appointments.

Although sexual activity screenings were associated with current teratogen use, pregnancy prevention counseling and emergency contraceptive counseling were not associated with teratogen use or reported sexual activity.

The survey also revealed that there were gaps in knowledge about the health effects of rheumatic medication. Of the patients on teratogens, 38% did not know that their medication could harm a fetus if they became pregnant. Only 9% of patients not on teratogens correctly answered that their medication would not harm a fetus.

Previous studies have also shown that rheumatology patients do not know that their medications can be teratogenic, noted Cuoghi Edens, MD, a rheumatologist at the University of Chicago, who sees both adult and pediatric patients. She was not involved with the study. The larger challenge is how to best educate patients, she said.

While hopefully a patient’s primary care provider is discussing these issues with them, these patients often see their rheumatologist more frequently and more consistently than other providers, Dr. Edens said.

UChicago Medicine

“We are sometimes the continuity of care for the patient versus their primary care, even though it should be a group effort of trying to some of these questions,” she said.

Conducting reproductive health screenings in pediatric rheumatology clinics can be difficult though, Dr. Edens noted, not only because of time constraints but also because parents often attend appointments with their child and likely have been for years. These screenings are most accurate when done one-on-one, so pivoting and removing the parents from the room can be awkward for providers, Dr. Edens said.

She advised that starting these conversations early on can be one way to ease into talking about reproductive health. In her own practice, Dr. Huynh sets aside time during appointments to speak with adolescent patients privately.

“We always discuss teratogenic medication. I always talk to them about the fact that I’m going to be doing pregnancy testing with their other screening labs because of the risks associated,” she said. “I also specifically set time aside for patients on teratogens to talk about emergency contraception and offer a prescription, if they’re interested.”

Dr. Huynh emphasized that providing easy access to emergency contraception is key. The ACR reproductive health guidelines — although geared toward adults — recommend discussing emergency contraception with patients, and Dr. Huynh advocates writing prescriptions for interested patients.

“They can fill it and have it easily accessible, so that there are no additional barriers, particularly for people who have these higher risks,” she said.

While emergency contraceptives are also available over the counter, it can be awkward for young people to ask for them, she said, and they can be expensive if not covered under insurance. Providing a prescription is one way to avoid those issues, Dr. Huynh said.

“Certainly, you have to have some parent buy-in, because if there is going to be a script, it’s probably going to be under insurance,” she said. “But in my experience, parents are happy to have it around as long as you’re talking it through with them as well as the young person.”

Dr. Huynh and Dr. Edens had no disclosures.

A version of this article appeared on Medscape.com.

Follicular occlusion, mast cell disease, and eczema were common presentations among patients with hypermobile Ehlers-Danlos syndrome (hEDS), in a study of nearly 500 individuals.

The genetic cause of hEDS, a common inherited connective tissue disorder, remains unknown, wrote Alan Snyder, MD, of the department of dermatology and dermatologic surgery at Medical University of South Carolina, Charleston, and colleagues.

Previous research suggests that changes in dermal mechanics predispose these patients to a range of skin conditions including mast cell activation disorder (MCAD) spectrum and chronic spontaneous urticaria, abnormal scars or wound healing, piezogenic papules, dyshidrosis, skin laxity or softness, easy bruising, local anesthesia resistance, keratosis pilaris, striae, and hidradenitis suppurativa, the researchers wrote.

However, data on these and other dermatologic manifestations of hEDS are limited, they said.

The diagnosis of hEDS will continue to be made more frequently and carefully, as the condition becomes more recognized and understood in the medical community, especially with anticipated capabilities of genetic testing, Dr. Snyder said in an interview.

“Being able to be aware of disease-specific comorbidities, such as those discovered in this study, allows providers to better stratify phenotypes and improve patient disease co-management,” he said.

In the study, published in the Journal of the American Academy of Dermatology, the researchers reviewed data on 1,364 patients with ICD-10 or ICD-9 codes for hEDS or EDS unspecified who were seen at a single institution between June 2005 and May 2022. Most of the patients were White (95.4%) and female (86.7%); the average age was 29.2 years.

Of the 1,364 patients included in the chart review, 497 (36.4%) had documented skin manifestations. Of these, 118 (24.2%) had disorders of follicular occlusion (12 had hidradenitis suppurativa, 32 had folliculitis, and 74 had acne); 112 (23%) had eczema or atopic dermatitis, 98 (19.7%) had mast cell disorder, 32 (6.4%) had psoriasis, and 32 (6.4%) had wound healing issues (16 had hypertrophic keloids/scarring, 5 had abscesses, 3 had abnormal bruising, and 8 had other would healing issues).

The study also included results of a multiple-choice patient survey from 1,354 individuals. In the survey, approximately two-thirds of patients reported abnormal scarring, abnormal wound healing, and cutaneous laxity (61.7%, 69.0%, and 71.0%, respectively).

The findings were limited by several factors including the retrospective study design, lack of testing to confirm hEDS diagnosis, and the potential interdisciplinary selection bias for diagnoses, the authors noted.

However, the results support previous studies showing increased rates of occlusive conditions in hEDS and higher rates of acne, folliculitis, and psoriasis, and highlight the need for clinician education to manage patients and promote better outcomes, the researchers concluded.

Data Enhance Clinical Awareness

“Given the increasingly understood relation between TH2-directed and mast-cell mediated diseases and hEDS, it was not necessarily a surprise to find the increased prevalence of atopy and mast cell disease, but rather an interesting confirmation, within the limitations that exist with retrospective chart review,” Dr. Snyder told this news organization. “While it may make some intuitive sense that certain cohorts with higher risk of HS may have a higher risk of acne, this had not been reported in the literature to date,” he noted. “Given the high levels of patient reported issues with scarring and wound healing, I was surprised that so few analogous diagnoses were physician-reported in the medical records.”

In clinical practice, “health care professionals and patients need to be aware hEDS is associated with high rates of eczematous, mast-cell mediated and follicular occlusive cutaneous disorders,” Dr. Snyder said in an interview. “There seems to be a discrepancy between patients and physician awareness of scarring or wound healing issues in this patient population,” he added.

Looking ahead, “we need to better research and characterize the various hEDS phenotypes to understand who is at highest risk for various TH2-mediated or follicular occlusive disorders,” said Dr. Snyder. “Moreover, a greater understanding is needed of the wound healing inadequacies that predispose these patients to poor outcomes during dermatologic surgery,” he said.

The study was supported by the Ehlers-Danlos Society and the Milton and Tamar Maltz Family Foundation. The researchers had no financial conflicts to disclose.

Follicular occlusion, mast cell disease, and eczema were common presentations among patients with hypermobile Ehlers-Danlos syndrome (hEDS), in a study of nearly 500 individuals.

The genetic cause of hEDS, a common inherited connective tissue disorder, remains unknown, wrote Alan Snyder, MD, of the department of dermatology and dermatologic surgery at Medical University of South Carolina, Charleston, and colleagues.

Previous research suggests that changes in dermal mechanics predispose these patients to a range of skin conditions including mast cell activation disorder (MCAD) spectrum and chronic spontaneous urticaria, abnormal scars or wound healing, piezogenic papules, dyshidrosis, skin laxity or softness, easy bruising, local anesthesia resistance, keratosis pilaris, striae, and hidradenitis suppurativa, the researchers wrote.

However, data on these and other dermatologic manifestations of hEDS are limited, they said.

The diagnosis of hEDS will continue to be made more frequently and carefully, as the condition becomes more recognized and understood in the medical community, especially with anticipated capabilities of genetic testing, Dr. Snyder said in an interview.

“Being able to be aware of disease-specific comorbidities, such as those discovered in this study, allows providers to better stratify phenotypes and improve patient disease co-management,” he said.

In the study, published in the Journal of the American Academy of Dermatology, the researchers reviewed data on 1,364 patients with ICD-10 or ICD-9 codes for hEDS or EDS unspecified who were seen at a single institution between June 2005 and May 2022. Most of the patients were White (95.4%) and female (86.7%); the average age was 29.2 years.

Of the 1,364 patients included in the chart review, 497 (36.4%) had documented skin manifestations. Of these, 118 (24.2%) had disorders of follicular occlusion (12 had hidradenitis suppurativa, 32 had folliculitis, and 74 had acne); 112 (23%) had eczema or atopic dermatitis, 98 (19.7%) had mast cell disorder, 32 (6.4%) had psoriasis, and 32 (6.4%) had wound healing issues (16 had hypertrophic keloids/scarring, 5 had abscesses, 3 had abnormal bruising, and 8 had other would healing issues).

The study also included results of a multiple-choice patient survey from 1,354 individuals. In the survey, approximately two-thirds of patients reported abnormal scarring, abnormal wound healing, and cutaneous laxity (61.7%, 69.0%, and 71.0%, respectively).

The findings were limited by several factors including the retrospective study design, lack of testing to confirm hEDS diagnosis, and the potential interdisciplinary selection bias for diagnoses, the authors noted.

However, the results support previous studies showing increased rates of occlusive conditions in hEDS and higher rates of acne, folliculitis, and psoriasis, and highlight the need for clinician education to manage patients and promote better outcomes, the researchers concluded.

Data Enhance Clinical Awareness

“Given the increasingly understood relation between TH2-directed and mast-cell mediated diseases and hEDS, it was not necessarily a surprise to find the increased prevalence of atopy and mast cell disease, but rather an interesting confirmation, within the limitations that exist with retrospective chart review,” Dr. Snyder told this news organization. “While it may make some intuitive sense that certain cohorts with higher risk of HS may have a higher risk of acne, this had not been reported in the literature to date,” he noted. “Given the high levels of patient reported issues with scarring and wound healing, I was surprised that so few analogous diagnoses were physician-reported in the medical records.”

In clinical practice, “health care professionals and patients need to be aware hEDS is associated with high rates of eczematous, mast-cell mediated and follicular occlusive cutaneous disorders,” Dr. Snyder said in an interview. “There seems to be a discrepancy between patients and physician awareness of scarring or wound healing issues in this patient population,” he added.

Looking ahead, “we need to better research and characterize the various hEDS phenotypes to understand who is at highest risk for various TH2-mediated or follicular occlusive disorders,” said Dr. Snyder. “Moreover, a greater understanding is needed of the wound healing inadequacies that predispose these patients to poor outcomes during dermatologic surgery,” he said.

The study was supported by the Ehlers-Danlos Society and the Milton and Tamar Maltz Family Foundation. The researchers had no financial conflicts to disclose.

Follicular occlusion, mast cell disease, and eczema were common presentations among patients with hypermobile Ehlers-Danlos syndrome (hEDS), in a study of nearly 500 individuals.

The genetic cause of hEDS, a common inherited connective tissue disorder, remains unknown, wrote Alan Snyder, MD, of the department of dermatology and dermatologic surgery at Medical University of South Carolina, Charleston, and colleagues.

Previous research suggests that changes in dermal mechanics predispose these patients to a range of skin conditions including mast cell activation disorder (MCAD) spectrum and chronic spontaneous urticaria, abnormal scars or wound healing, piezogenic papules, dyshidrosis, skin laxity or softness, easy bruising, local anesthesia resistance, keratosis pilaris, striae, and hidradenitis suppurativa, the researchers wrote.

However, data on these and other dermatologic manifestations of hEDS are limited, they said.

The diagnosis of hEDS will continue to be made more frequently and carefully, as the condition becomes more recognized and understood in the medical community, especially with anticipated capabilities of genetic testing, Dr. Snyder said in an interview.

“Being able to be aware of disease-specific comorbidities, such as those discovered in this study, allows providers to better stratify phenotypes and improve patient disease co-management,” he said.

In the study, published in the Journal of the American Academy of Dermatology, the researchers reviewed data on 1,364 patients with ICD-10 or ICD-9 codes for hEDS or EDS unspecified who were seen at a single institution between June 2005 and May 2022. Most of the patients were White (95.4%) and female (86.7%); the average age was 29.2 years.

Of the 1,364 patients included in the chart review, 497 (36.4%) had documented skin manifestations. Of these, 118 (24.2%) had disorders of follicular occlusion (12 had hidradenitis suppurativa, 32 had folliculitis, and 74 had acne); 112 (23%) had eczema or atopic dermatitis, 98 (19.7%) had mast cell disorder, 32 (6.4%) had psoriasis, and 32 (6.4%) had wound healing issues (16 had hypertrophic keloids/scarring, 5 had abscesses, 3 had abnormal bruising, and 8 had other would healing issues).

The study also included results of a multiple-choice patient survey from 1,354 individuals. In the survey, approximately two-thirds of patients reported abnormal scarring, abnormal wound healing, and cutaneous laxity (61.7%, 69.0%, and 71.0%, respectively).

The findings were limited by several factors including the retrospective study design, lack of testing to confirm hEDS diagnosis, and the potential interdisciplinary selection bias for diagnoses, the authors noted.

However, the results support previous studies showing increased rates of occlusive conditions in hEDS and higher rates of acne, folliculitis, and psoriasis, and highlight the need for clinician education to manage patients and promote better outcomes, the researchers concluded.

Data Enhance Clinical Awareness

“Given the increasingly understood relation between TH2-directed and mast-cell mediated diseases and hEDS, it was not necessarily a surprise to find the increased prevalence of atopy and mast cell disease, but rather an interesting confirmation, within the limitations that exist with retrospective chart review,” Dr. Snyder told this news organization. “While it may make some intuitive sense that certain cohorts with higher risk of HS may have a higher risk of acne, this had not been reported in the literature to date,” he noted. “Given the high levels of patient reported issues with scarring and wound healing, I was surprised that so few analogous diagnoses were physician-reported in the medical records.”

In clinical practice, “health care professionals and patients need to be aware hEDS is associated with high rates of eczematous, mast-cell mediated and follicular occlusive cutaneous disorders,” Dr. Snyder said in an interview. “There seems to be a discrepancy between patients and physician awareness of scarring or wound healing issues in this patient population,” he added.

Looking ahead, “we need to better research and characterize the various hEDS phenotypes to understand who is at highest risk for various TH2-mediated or follicular occlusive disorders,” said Dr. Snyder. “Moreover, a greater understanding is needed of the wound healing inadequacies that predispose these patients to poor outcomes during dermatologic surgery,” he said.

The study was supported by the Ehlers-Danlos Society and the Milton and Tamar Maltz Family Foundation. The researchers had no financial conflicts to disclose.