Rare Diseases

SEATTLE – Tissue accumulation of advanced glycation end products (AGEs) is associated with the presence of hypercortisolism, suggesting a potential future noninvasive method to assist in the diagnosis of Cushing syndrome, new research suggests.
 

Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.

The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.

“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.

“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.

Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”

However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.

Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
 

More work will be needed

Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.

“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”

Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”

But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”

Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.

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

SEATTLE – Tissue accumulation of advanced glycation end products (AGEs) is associated with the presence of hypercortisolism, suggesting a potential future noninvasive method to assist in the diagnosis of Cushing syndrome, new research suggests.
 

Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.

The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.

“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.

“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.

Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”

However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.

Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
 

More work will be needed

Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.

“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”

Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”

But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”

Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.

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

SEATTLE – Tissue accumulation of advanced glycation end products (AGEs) is associated with the presence of hypercortisolism, suggesting a potential future noninvasive method to assist in the diagnosis of Cushing syndrome, new research suggests.
 

Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.

The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.

“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.

“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.

Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”

However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.

Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
 

More work will be needed

Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.

“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”

Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”

But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”

Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with confirmed Fabry disease.

Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, the heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.

Elfabrio delivers a functional version of GLA. It’s given by intravenous infusion every 2 weeks.

Evidence for safety, tolerability, and efficacy of Elfabrio stems from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow up treatment.

It has been studied in both ERT-naïve and ERT-experienced patients. In one head-to-head trial, Elfabrio was non-inferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.

“The totality of clinical data suggests that Elfabrio has the potential to be a long-lasting therapy,” Dror Bashan, president and CEO of Protalix, said in the statement.

Patients treated with Elfabrio have experienced hypersensitivity reactions, including anaphylaxis. In clinical trials, 20 (14%) patients treated with Elfabrio experienced hypersensitivity reactions; 4 patients (3%) experienced anaphylaxis reactions that occurred within 5-40 minutes of the start of the initial infusion.

Before administering Elfabrio, pretreatment with antihistamines, antipyretics, and/or corticosteroids should be considered, the label advises.

Patients and caregivers should be informed of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions and instructed to seek medical care immediately if such symptoms occur.

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitoring serum creatinine and urinary protein-to-creatinine ratio is advised. If glomerulonephritis is suspected, treatment should be stopped until a diagnostic evaluation can be conducted.

Full prescribing information is available online.

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

The U.S. Food and Drug Administration has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with confirmed Fabry disease.

Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, the heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.

Elfabrio delivers a functional version of GLA. It’s given by intravenous infusion every 2 weeks.

Evidence for safety, tolerability, and efficacy of Elfabrio stems from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow up treatment.

It has been studied in both ERT-naïve and ERT-experienced patients. In one head-to-head trial, Elfabrio was non-inferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.

“The totality of clinical data suggests that Elfabrio has the potential to be a long-lasting therapy,” Dror Bashan, president and CEO of Protalix, said in the statement.

Patients treated with Elfabrio have experienced hypersensitivity reactions, including anaphylaxis. In clinical trials, 20 (14%) patients treated with Elfabrio experienced hypersensitivity reactions; 4 patients (3%) experienced anaphylaxis reactions that occurred within 5-40 minutes of the start of the initial infusion.

Before administering Elfabrio, pretreatment with antihistamines, antipyretics, and/or corticosteroids should be considered, the label advises.

Patients and caregivers should be informed of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions and instructed to seek medical care immediately if such symptoms occur.

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitoring serum creatinine and urinary protein-to-creatinine ratio is advised. If glomerulonephritis is suspected, treatment should be stopped until a diagnostic evaluation can be conducted.

Full prescribing information is available online.

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

The U.S. Food and Drug Administration has approved pegunigalsidase alfa (Elfabrio, Chiesi Global Rare Diseases/Protalix BioTherapeutics), an enzyme replacement therapy (ERT) to treat adults with confirmed Fabry disease.

Fabry disease is a rare inherited X-linked lysosomal disorder caused by a deficiency of the enzyme alpha-galactosidase A (GLA), which leads to the buildup of globotriaosylceramide (GL-3) in blood vessels, kidneys, the heart, nerves, and other organs, increasing the risk for kidney failure, myocardial infarction, stroke, and other problems.

Elfabrio delivers a functional version of GLA. It’s given by intravenous infusion every 2 weeks.

Evidence for safety, tolerability, and efficacy of Elfabrio stems from a comprehensive clinical program in more than 140 patients with up to 7.5 years of follow up treatment.

It has been studied in both ERT-naïve and ERT-experienced patients. In one head-to-head trial, Elfabrio was non-inferior in safety and efficacy to agalsidase beta (Fabrazyme, Sanofi Genzyme), the companies said in a press statement announcing approval.

“The totality of clinical data suggests that Elfabrio has the potential to be a long-lasting therapy,” Dror Bashan, president and CEO of Protalix, said in the statement.

Patients treated with Elfabrio have experienced hypersensitivity reactions, including anaphylaxis. In clinical trials, 20 (14%) patients treated with Elfabrio experienced hypersensitivity reactions; 4 patients (3%) experienced anaphylaxis reactions that occurred within 5-40 minutes of the start of the initial infusion.

Before administering Elfabrio, pretreatment with antihistamines, antipyretics, and/or corticosteroids should be considered, the label advises.

Patients and caregivers should be informed of the signs and symptoms of hypersensitivity reactions and infusion-associated reactions and instructed to seek medical care immediately if such symptoms occur.

A case of membranoproliferative glomerulonephritis with immune depositions in the kidney was reported during clinical trials. Monitoring serum creatinine and urinary protein-to-creatinine ratio is advised. If glomerulonephritis is suspected, treatment should be stopped until a diagnostic evaluation can be conducted.

Full prescribing information is available online.

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

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Use of intravenous immunoglobulin (IVIG) had no apparent effect on the risk of venous thromboembolism (VTE) in adults with dermatomyositis (DM), based on data from more than 400 individuals.

DM has been associated with an increased risk of VTE in previous studies, wrote Elizabeth T. Rotrosen, of Boston University and Brigham and Women’s Hospital, Boston, and colleagues. Although IVIG is often effective for DM patients with recalcitrant disease, it carries a boxed warning for increased thrombosis risk; however, the association between IVIG use and VTE risk in DM has not been well examined, the researchers said.

In a study published in JAMA Dermatology, the researchers identified 458 adults with DM based on the European Alliance of Associations for Reumatology/American College of Rheumatology criteria. The mean age of the participants was 51.8 years, 76% were female, and 82% were White. Of these, 178 were treated with IVIG and 280 were not. The mean duration of IVIG treatment was 32.9 months. The researchers used the chi square test to test for independence between binary variables, the Pearson chi square test to test for independence between categorical variables, and the unpaired t test to compare continuous variables in their statistical analysis.

A total of 23 patients experienced DM-associated VTEs; 6 in the IVIG group and 17 in the non-IVIG group (3.4% vs. 5.7%, P = .20), a nonsignificant difference. The patients in the IVIG group who experienced a DM-associated VTE all underwent IVIG treatment within 4 weeks before the event.

bong hyunjung/iStock/Getty Images

The study findings were limited by several factors, including the retrospective design and small number of VTEs. Prospective studies are needed for better assessment of the VTE risk in patients with DM treated with IVIG, the researchers noted. However, the study is the largest known to explore the association between IVIG use and VTE risk in patients with DM, they said, and the results suggest that clinicians may continue IVIG use in these patients with considerations of risks and benefits on an individual basis.

The study received no outside funding. Ms. Rotrosen had no financial conflicts to disclose. Two coauthors reported financial relationships with Pfizer unrelated to this study.

Use of intravenous immunoglobulin (IVIG) had no apparent effect on the risk of venous thromboembolism (VTE) in adults with dermatomyositis (DM), based on data from more than 400 individuals.

DM has been associated with an increased risk of VTE in previous studies, wrote Elizabeth T. Rotrosen, of Boston University and Brigham and Women’s Hospital, Boston, and colleagues. Although IVIG is often effective for DM patients with recalcitrant disease, it carries a boxed warning for increased thrombosis risk; however, the association between IVIG use and VTE risk in DM has not been well examined, the researchers said.

In a study published in JAMA Dermatology, the researchers identified 458 adults with DM based on the European Alliance of Associations for Reumatology/American College of Rheumatology criteria. The mean age of the participants was 51.8 years, 76% were female, and 82% were White. Of these, 178 were treated with IVIG and 280 were not. The mean duration of IVIG treatment was 32.9 months. The researchers used the chi square test to test for independence between binary variables, the Pearson chi square test to test for independence between categorical variables, and the unpaired t test to compare continuous variables in their statistical analysis.

A total of 23 patients experienced DM-associated VTEs; 6 in the IVIG group and 17 in the non-IVIG group (3.4% vs. 5.7%, P = .20), a nonsignificant difference. The patients in the IVIG group who experienced a DM-associated VTE all underwent IVIG treatment within 4 weeks before the event.

bong hyunjung/iStock/Getty Images

The study findings were limited by several factors, including the retrospective design and small number of VTEs. Prospective studies are needed for better assessment of the VTE risk in patients with DM treated with IVIG, the researchers noted. However, the study is the largest known to explore the association between IVIG use and VTE risk in patients with DM, they said, and the results suggest that clinicians may continue IVIG use in these patients with considerations of risks and benefits on an individual basis.

The study received no outside funding. Ms. Rotrosen had no financial conflicts to disclose. Two coauthors reported financial relationships with Pfizer unrelated to this study.

Use of intravenous immunoglobulin (IVIG) had no apparent effect on the risk of venous thromboembolism (VTE) in adults with dermatomyositis (DM), based on data from more than 400 individuals.

DM has been associated with an increased risk of VTE in previous studies, wrote Elizabeth T. Rotrosen, of Boston University and Brigham and Women’s Hospital, Boston, and colleagues. Although IVIG is often effective for DM patients with recalcitrant disease, it carries a boxed warning for increased thrombosis risk; however, the association between IVIG use and VTE risk in DM has not been well examined, the researchers said.

In a study published in JAMA Dermatology, the researchers identified 458 adults with DM based on the European Alliance of Associations for Reumatology/American College of Rheumatology criteria. The mean age of the participants was 51.8 years, 76% were female, and 82% were White. Of these, 178 were treated with IVIG and 280 were not. The mean duration of IVIG treatment was 32.9 months. The researchers used the chi square test to test for independence between binary variables, the Pearson chi square test to test for independence between categorical variables, and the unpaired t test to compare continuous variables in their statistical analysis.

A total of 23 patients experienced DM-associated VTEs; 6 in the IVIG group and 17 in the non-IVIG group (3.4% vs. 5.7%, P = .20), a nonsignificant difference. The patients in the IVIG group who experienced a DM-associated VTE all underwent IVIG treatment within 4 weeks before the event.

bong hyunjung/iStock/Getty Images

The study findings were limited by several factors, including the retrospective design and small number of VTEs. Prospective studies are needed for better assessment of the VTE risk in patients with DM treated with IVIG, the researchers noted. However, the study is the largest known to explore the association between IVIG use and VTE risk in patients with DM, they said, and the results suggest that clinicians may continue IVIG use in these patients with considerations of risks and benefits on an individual basis.

The study received no outside funding. Ms. Rotrosen had no financial conflicts to disclose. Two coauthors reported financial relationships with Pfizer unrelated to this study.

MANCHESTER, ENGLAND – An age-appropriate version of the Lupus Low Disease Activity State (LLDAS) has been developed by an international task force that will hopefully enable childhood-onset systemic lupus erythematosus (cSLE) to be treated to target in the near future.

The new childhood LLDAS (cLLDAS) has been purposefully developed to align with that already used for adults, Eve Smith, MBChB, PhD, explained at the annual meeting of the British Society for Rheumatology.

“There’s a lot of compelling data that’s accumulating from adult lupus and increasingly from childhood lupus that [treat to target] might be a good idea,” said Dr. Smith, who is a senior clinical fellow and honorary consultant at the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust Hospital, also in Liverpool.
 

Urgent need to improve childhood lupus outcomes

“We urgently need to do something to try and improve outcomes for children,” Dr. Smith said.

“We know that childhood lupus patients have got higher disease activity as compared to adults; they have a greater medication burden, particularly steroids; and they tend to have more severe organ manifestations,” she added.

Moreover, data show that one-fifth of pediatric patients with lupus have already accrued early damage, and there is much higher mortality associated with childhood lupus than there is with adult lupus.

“So, really we want to use treat to target as a way to try and improve on these aspects,” Dr. Smith said.

The treat-to-target (T2T) approach is not a new idea in lupus, with a lot of work already done in adult patients. One large study of more than 3,300 patients conducted in 13 countries has shown that patients who never achieve LLDAS are more likely to have high levels of damage, greater glucocorticoid use, worse quality of life, and higher mortality than are those who do.

Conversely, data have also shown that achieving a LLDAS is associated with a reduction in the risk for new damage, flares, and hospitalization, as well as reducing health care costs and improving patients’ overall health-related quality of life.

T2T is a recognized approach in European adult SLE guidelines, Dr. Smith said, although the approach has not really been fully realized as of yet, even in adult practice.
 

The cSLE T2T international task force and cLLDAS definition

With evidence accumulating on the benefits of getting children with SLE to a low disease activity state, Dr. Smith and colleague Michael Beresford, MBChB, PhD, Brough Chair, Professor of Child Health at the University of Liverpool, put out a call to develop a task force to look into the feasibility of a T2T approach.

“We had a really enthusiastic response internationally, which we were really encouraged by,” Dr. Smith said, “and we now lead a task force of 20 experts from across all five continents, and we have really strong patient involvement.”

Through a consensus process, an international cSLE T2T Task Force agreed on overarching principles and points to consider that will “lay the foundation for future T2T approaches in cSLE,” according to the recommendations statement, which was endorsed by the Paediatric Rheumatology European Society.

Next, they looked to develop an age-appropriate definition for low disease activity.

“We’re deliberately wanting to maintain sufficient unity with the adult definition, so that we could facilitate life-course studies,” said Dr. Smith, who presented the results of a literature review and series of Delphi surveys at the meeting.

The conceptual definition of cLLDAS is similar to adults in describing it as a sustained state that is associated with a low likelihood of adverse outcome, Dr. Smith said, but with the added wording of “considering disease activity, damage, and medication toxicity.”

The definition is achieved when the SLE Disease Activity Index-2K is ≤ 4 and there is no activity in major organ systems; there are no new features of lupus disease activity since the last assessment; there is a score of ≤ 1 on Physician Global Assessment; steroid doses are ≤ 0.15 mg/kg/day or a maximum of 7.5 mg/day (whichever is lower); and immunosuppressive treatment is stable, with any changes to medication only because of side effects, adherence, changes in weight, or when in the process of reaching a target dose.

“It’s all very well having a definition, but you need to think about how that will work in practice,” Dr. Smith said. This is something that the task force is thinking about very carefully.

The task force next aims to validate the cLLDAS definition, form an extensive research agenda to inform the T2T methods, and develop innovative methods to apply the approach in practice.

The work is supported by the Wellcome Trust, National Institutes for Health Research, Versus Arthritis, and the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity. Dr. Smith reported no relevant financial relationships.
 

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

MANCHESTER, ENGLAND – An age-appropriate version of the Lupus Low Disease Activity State (LLDAS) has been developed by an international task force that will hopefully enable childhood-onset systemic lupus erythematosus (cSLE) to be treated to target in the near future.

The new childhood LLDAS (cLLDAS) has been purposefully developed to align with that already used for adults, Eve Smith, MBChB, PhD, explained at the annual meeting of the British Society for Rheumatology.

“There’s a lot of compelling data that’s accumulating from adult lupus and increasingly from childhood lupus that [treat to target] might be a good idea,” said Dr. Smith, who is a senior clinical fellow and honorary consultant at the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust Hospital, also in Liverpool.
 

Urgent need to improve childhood lupus outcomes

“We urgently need to do something to try and improve outcomes for children,” Dr. Smith said.

“We know that childhood lupus patients have got higher disease activity as compared to adults; they have a greater medication burden, particularly steroids; and they tend to have more severe organ manifestations,” she added.

Moreover, data show that one-fifth of pediatric patients with lupus have already accrued early damage, and there is much higher mortality associated with childhood lupus than there is with adult lupus.

“So, really we want to use treat to target as a way to try and improve on these aspects,” Dr. Smith said.

The treat-to-target (T2T) approach is not a new idea in lupus, with a lot of work already done in adult patients. One large study of more than 3,300 patients conducted in 13 countries has shown that patients who never achieve LLDAS are more likely to have high levels of damage, greater glucocorticoid use, worse quality of life, and higher mortality than are those who do.

Conversely, data have also shown that achieving a LLDAS is associated with a reduction in the risk for new damage, flares, and hospitalization, as well as reducing health care costs and improving patients’ overall health-related quality of life.

T2T is a recognized approach in European adult SLE guidelines, Dr. Smith said, although the approach has not really been fully realized as of yet, even in adult practice.
 

The cSLE T2T international task force and cLLDAS definition

With evidence accumulating on the benefits of getting children with SLE to a low disease activity state, Dr. Smith and colleague Michael Beresford, MBChB, PhD, Brough Chair, Professor of Child Health at the University of Liverpool, put out a call to develop a task force to look into the feasibility of a T2T approach.

“We had a really enthusiastic response internationally, which we were really encouraged by,” Dr. Smith said, “and we now lead a task force of 20 experts from across all five continents, and we have really strong patient involvement.”

Through a consensus process, an international cSLE T2T Task Force agreed on overarching principles and points to consider that will “lay the foundation for future T2T approaches in cSLE,” according to the recommendations statement, which was endorsed by the Paediatric Rheumatology European Society.

Next, they looked to develop an age-appropriate definition for low disease activity.

“We’re deliberately wanting to maintain sufficient unity with the adult definition, so that we could facilitate life-course studies,” said Dr. Smith, who presented the results of a literature review and series of Delphi surveys at the meeting.

The conceptual definition of cLLDAS is similar to adults in describing it as a sustained state that is associated with a low likelihood of adverse outcome, Dr. Smith said, but with the added wording of “considering disease activity, damage, and medication toxicity.”

The definition is achieved when the SLE Disease Activity Index-2K is ≤ 4 and there is no activity in major organ systems; there are no new features of lupus disease activity since the last assessment; there is a score of ≤ 1 on Physician Global Assessment; steroid doses are ≤ 0.15 mg/kg/day or a maximum of 7.5 mg/day (whichever is lower); and immunosuppressive treatment is stable, with any changes to medication only because of side effects, adherence, changes in weight, or when in the process of reaching a target dose.

“It’s all very well having a definition, but you need to think about how that will work in practice,” Dr. Smith said. This is something that the task force is thinking about very carefully.

The task force next aims to validate the cLLDAS definition, form an extensive research agenda to inform the T2T methods, and develop innovative methods to apply the approach in practice.

The work is supported by the Wellcome Trust, National Institutes for Health Research, Versus Arthritis, and the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity. Dr. Smith reported no relevant financial relationships.
 

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

MANCHESTER, ENGLAND – An age-appropriate version of the Lupus Low Disease Activity State (LLDAS) has been developed by an international task force that will hopefully enable childhood-onset systemic lupus erythematosus (cSLE) to be treated to target in the near future.

The new childhood LLDAS (cLLDAS) has been purposefully developed to align with that already used for adults, Eve Smith, MBChB, PhD, explained at the annual meeting of the British Society for Rheumatology.

“There’s a lot of compelling data that’s accumulating from adult lupus and increasingly from childhood lupus that [treat to target] might be a good idea,” said Dr. Smith, who is a senior clinical fellow and honorary consultant at the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust Hospital, also in Liverpool.
 

Urgent need to improve childhood lupus outcomes

“We urgently need to do something to try and improve outcomes for children,” Dr. Smith said.

“We know that childhood lupus patients have got higher disease activity as compared to adults; they have a greater medication burden, particularly steroids; and they tend to have more severe organ manifestations,” she added.

Moreover, data show that one-fifth of pediatric patients with lupus have already accrued early damage, and there is much higher mortality associated with childhood lupus than there is with adult lupus.

“So, really we want to use treat to target as a way to try and improve on these aspects,” Dr. Smith said.

The treat-to-target (T2T) approach is not a new idea in lupus, with a lot of work already done in adult patients. One large study of more than 3,300 patients conducted in 13 countries has shown that patients who never achieve LLDAS are more likely to have high levels of damage, greater glucocorticoid use, worse quality of life, and higher mortality than are those who do.

Conversely, data have also shown that achieving a LLDAS is associated with a reduction in the risk for new damage, flares, and hospitalization, as well as reducing health care costs and improving patients’ overall health-related quality of life.

T2T is a recognized approach in European adult SLE guidelines, Dr. Smith said, although the approach has not really been fully realized as of yet, even in adult practice.
 

The cSLE T2T international task force and cLLDAS definition

With evidence accumulating on the benefits of getting children with SLE to a low disease activity state, Dr. Smith and colleague Michael Beresford, MBChB, PhD, Brough Chair, Professor of Child Health at the University of Liverpool, put out a call to develop a task force to look into the feasibility of a T2T approach.

“We had a really enthusiastic response internationally, which we were really encouraged by,” Dr. Smith said, “and we now lead a task force of 20 experts from across all five continents, and we have really strong patient involvement.”

Through a consensus process, an international cSLE T2T Task Force agreed on overarching principles and points to consider that will “lay the foundation for future T2T approaches in cSLE,” according to the recommendations statement, which was endorsed by the Paediatric Rheumatology European Society.

Next, they looked to develop an age-appropriate definition for low disease activity.

“We’re deliberately wanting to maintain sufficient unity with the adult definition, so that we could facilitate life-course studies,” said Dr. Smith, who presented the results of a literature review and series of Delphi surveys at the meeting.

The conceptual definition of cLLDAS is similar to adults in describing it as a sustained state that is associated with a low likelihood of adverse outcome, Dr. Smith said, but with the added wording of “considering disease activity, damage, and medication toxicity.”

The definition is achieved when the SLE Disease Activity Index-2K is ≤ 4 and there is no activity in major organ systems; there are no new features of lupus disease activity since the last assessment; there is a score of ≤ 1 on Physician Global Assessment; steroid doses are ≤ 0.15 mg/kg/day or a maximum of 7.5 mg/day (whichever is lower); and immunosuppressive treatment is stable, with any changes to medication only because of side effects, adherence, changes in weight, or when in the process of reaching a target dose.

“It’s all very well having a definition, but you need to think about how that will work in practice,” Dr. Smith said. This is something that the task force is thinking about very carefully.

The task force next aims to validate the cLLDAS definition, form an extensive research agenda to inform the T2T methods, and develop innovative methods to apply the approach in practice.

The work is supported by the Wellcome Trust, National Institutes for Health Research, Versus Arthritis, and the University of Liverpool, Alder Hey Children’s NHS Foundation Trust and the Alder Hey Charity. Dr. Smith reported no relevant financial relationships.
 

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

The incidence and prevalence of IgG4-related disease each rose considerably from 2015 to 2019 in the United States, and the risk of death in those with the immune-mediated condition is about 2.5 times higher than those who are not affected, based on an analysis of claims data from commercially insured adults.

The first population-based study of IgG4-RD incidence, prevalence, and mortality establishes “key benchmarks for informing the diagnosis and management of patients” with a condition “that causes fibrosing inflammatory lesions at nearly any anatomic site,” and wasn’t initially described until 2001, Zachary S. Wallace, MD, and associates said in Annals of the Rheumatic Diseases.

The increases in incidence and prevalence likely reflected increased disease awareness, they suggested. Overall U.S. incidence was 1.2 per 100,000 person-years for the 5-year period of 2015-2019, rising 86% from 0.78 per 100,000 person-years to 1.45 in 2018 before dropping to 1.39 in 2019. The change in prevalence was even greater, increasing 122% from 2.41 per 100,000 persons in 2015 to 5.34 per 100,000 in 2019, the investigators said.

Previous studies had indicated that the majority of patients with IgG4-RD were male, but the current study, using Optum’s Clinformatics Data Mart, which includes commercial health plan and Medicare Advantage members in all 50 states, showed that both incidence and prevalence (see graph) were higher among women, noted Dr. Wallace of Massachusetts General Hospital, Boston, and associates. They identified 524 patients (57.6% female) in the database who met the criteria for IgG4-RD from Jan. 1, 2010, to Dec. 31, 2019.

Incidence over the course of the study “was similar in patients identified as Asian or White but lower in those identified as Black or Hispanic,” they noted, adding that “the prevalence of IgG4-RD during this period reflected similar trends.” A jump in prevalence from 2018 to 2019, however, left White patients with a much higher rate (6.13 per 100,000 persons) than Asian patients (4.54 per 100,000), Black patients (3.42), and Hispanic patients (3.02).

For the mortality analysis, 516 patients with IgG4-RD were age-, sex-, and race-matched with 5,160 patients without IgG4-RD. Mortality was 3.42 and 1.46 per 100 person-years, respectively, over the 5.5 years of follow-up, so IgG4-RD was associated with a 2.5-fold higher risk of death. “The association of IgG4-RD with a higher risk of death was observed across the age spectrum and among both male and female patients,” the researchers said.

The incidence and prevalence of IgG4-related disease each rose considerably from 2015 to 2019 in the United States, and the risk of death in those with the immune-mediated condition is about 2.5 times higher than those who are not affected, based on an analysis of claims data from commercially insured adults.

The first population-based study of IgG4-RD incidence, prevalence, and mortality establishes “key benchmarks for informing the diagnosis and management of patients” with a condition “that causes fibrosing inflammatory lesions at nearly any anatomic site,” and wasn’t initially described until 2001, Zachary S. Wallace, MD, and associates said in Annals of the Rheumatic Diseases.

The increases in incidence and prevalence likely reflected increased disease awareness, they suggested. Overall U.S. incidence was 1.2 per 100,000 person-years for the 5-year period of 2015-2019, rising 86% from 0.78 per 100,000 person-years to 1.45 in 2018 before dropping to 1.39 in 2019. The change in prevalence was even greater, increasing 122% from 2.41 per 100,000 persons in 2015 to 5.34 per 100,000 in 2019, the investigators said.

Previous studies had indicated that the majority of patients with IgG4-RD were male, but the current study, using Optum’s Clinformatics Data Mart, which includes commercial health plan and Medicare Advantage members in all 50 states, showed that both incidence and prevalence (see graph) were higher among women, noted Dr. Wallace of Massachusetts General Hospital, Boston, and associates. They identified 524 patients (57.6% female) in the database who met the criteria for IgG4-RD from Jan. 1, 2010, to Dec. 31, 2019.

Incidence over the course of the study “was similar in patients identified as Asian or White but lower in those identified as Black or Hispanic,” they noted, adding that “the prevalence of IgG4-RD during this period reflected similar trends.” A jump in prevalence from 2018 to 2019, however, left White patients with a much higher rate (6.13 per 100,000 persons) than Asian patients (4.54 per 100,000), Black patients (3.42), and Hispanic patients (3.02).

For the mortality analysis, 516 patients with IgG4-RD were age-, sex-, and race-matched with 5,160 patients without IgG4-RD. Mortality was 3.42 and 1.46 per 100 person-years, respectively, over the 5.5 years of follow-up, so IgG4-RD was associated with a 2.5-fold higher risk of death. “The association of IgG4-RD with a higher risk of death was observed across the age spectrum and among both male and female patients,” the researchers said.

The incidence and prevalence of IgG4-related disease each rose considerably from 2015 to 2019 in the United States, and the risk of death in those with the immune-mediated condition is about 2.5 times higher than those who are not affected, based on an analysis of claims data from commercially insured adults.

The first population-based study of IgG4-RD incidence, prevalence, and mortality establishes “key benchmarks for informing the diagnosis and management of patients” with a condition “that causes fibrosing inflammatory lesions at nearly any anatomic site,” and wasn’t initially described until 2001, Zachary S. Wallace, MD, and associates said in Annals of the Rheumatic Diseases.

The increases in incidence and prevalence likely reflected increased disease awareness, they suggested. Overall U.S. incidence was 1.2 per 100,000 person-years for the 5-year period of 2015-2019, rising 86% from 0.78 per 100,000 person-years to 1.45 in 2018 before dropping to 1.39 in 2019. The change in prevalence was even greater, increasing 122% from 2.41 per 100,000 persons in 2015 to 5.34 per 100,000 in 2019, the investigators said.

Previous studies had indicated that the majority of patients with IgG4-RD were male, but the current study, using Optum’s Clinformatics Data Mart, which includes commercial health plan and Medicare Advantage members in all 50 states, showed that both incidence and prevalence (see graph) were higher among women, noted Dr. Wallace of Massachusetts General Hospital, Boston, and associates. They identified 524 patients (57.6% female) in the database who met the criteria for IgG4-RD from Jan. 1, 2010, to Dec. 31, 2019.

Incidence over the course of the study “was similar in patients identified as Asian or White but lower in those identified as Black or Hispanic,” they noted, adding that “the prevalence of IgG4-RD during this period reflected similar trends.” A jump in prevalence from 2018 to 2019, however, left White patients with a much higher rate (6.13 per 100,000 persons) than Asian patients (4.54 per 100,000), Black patients (3.42), and Hispanic patients (3.02).

For the mortality analysis, 516 patients with IgG4-RD were age-, sex-, and race-matched with 5,160 patients without IgG4-RD. Mortality was 3.42 and 1.46 per 100 person-years, respectively, over the 5.5 years of follow-up, so IgG4-RD was associated with a 2.5-fold higher risk of death. “The association of IgG4-RD with a higher risk of death was observed across the age spectrum and among both male and female patients,” the researchers said.

What do green monkeys, fruit bats, and python caves all have in common? All have been implicated in outbreaks as transmission sources of the rare but deadly Marburg virus. Marburg virus is in the same Filoviridae family of highly pathogenic RNA viruses as Ebola virus, and similarly can cause a rapidly progressive and fatal viral hemorrhagic fever.

In the first reported Marburg outbreak in 1967, laboratory workers in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia, developed severe febrile illnesses with massive hemorrhage and multiorgan system dysfunction after contact with infected African green monkeys imported from Uganda. Since the first discovery of Marburg virus, there have been over 14 Marburg virus disease (MVD) outbreaks worldwide with nearly 600 cases and case fatality rates of 23%-90%.

The majority of MVD outbreaks have occurred in sub-Saharan Africa, and primarily in three African countries: Angola, the Democratic Republic of Congo, and Uganda. In sub-Saharan Africa, these sporadic outbreaks have had high case fatality rates (up to 80%-90%) and been linked to human exposure to the oral secretions or urinary/fecal droppings of Egyptian fruit bats (Rousettus aegyptiacus), the animal reservoir for Marburg virus. These exposures have primarily occurred among miners or tourists frequenting bat-infested mines or caves, including Uganda’s python cave, where Centers for Disease Control and Prevention investigators have conducted ecological studies on Marburg-infected bats. Person-to-person transmission occurs from direct contact with the blood or bodily fluids of an infected person or contact with a contaminated object (for example, unsterilized needles and syringes in a large nosocomial outbreak in Angola).

On April 6, 2023, the CDC issued a Health Advisory for U.S. clinicians and public health departments regarding two separate MVD outbreaks in Equatorial Guinea and Tanzania. These first-ever MVD outbreaks in both West and East African countries appear to be epidemiologically unrelated. As of March 24, 2023, in Equatorial Guinea, a total of 15 confirmed cases, including 11 deaths, and 23 probable cases, all deceased, have been identified in multiple districts since the outbreak declaration in February 2023. In Tanzania, a total of eight cases, including five deaths, have been reported among villagers in a northwest region since the outbreak declaration in March 2023. While so far cases in the Tanzania MVD outbreak have been epidemiologically linked, in Equatorial Guinea some cases have no identified epidemiological links, raising concern for ongoing community spread.

To date, no cases in these outbreaks have been reported in the United States or outside the affected countries. Overall, the risk of MVD in nonendemic countries, like the United States, is low but there is still a risk of importation. As of May 2, 2023, CDC has issued a Level 2 travel alert (practice enhanced precautions) for Marburg in Equatorial Guinea and a Level 1 travel watch (practice usual precautions) for Marburg in Tanzania. Travelers to these countries are advised to avoid nonessential travel to areas with active outbreaks and practice preventative measures, including avoiding contact with sick people, blood and bodily fluids, dead bodies, fruit bats, and nonhuman primates. International travelers returning to the United States from these countries are advised to self-monitor for Marburg symptoms during travel and for 21 days after country departure. Travelers who develop signs or symptoms of MVD should immediately self-isolate and contact their local health department or clinician.

So, how should clinicians manage such return travelers? In the setting of these new MVD outbreaks in sub-Saharan Africa, what do U.S. clinicians need to know? Clinicians should consider MVD in the differential diagnosis of ill patients with a compatible exposure history and clinical presentation. A detailed exposure history should be obtained to determine if patients have been to an area with an active MVD outbreak during their incubation period (in the past 21 days), had concerning epidemiologic risk factors (for example, presence at funerals, health care facilities, in mines/caves) while in the affected area, and/or had contact with a suspected or confirmed MVD case.

Clinical diagnosis of MVD is challenging as the initial dry symptoms of infection are nonspecific (fever, influenza-like illness, malaise, anorexia, etc.) and can resemble other febrile infectious illnesses. Similarly, presenting alternative or concurrent infections, particularly in febrile return travelers, include malaria, Lassa fever, typhoid, and measles. From these nonspecific symptoms, patients with MVD can then progress to the more severe wet symptoms (for example, vomiting, diarrhea, and bleeding). Common clinical features of MVD have been described based on the clinical presentation and course of cases in MVD outbreaks. Notably, in the original Marburg outbreak, maculopapular rash and conjunctival injection were early patient symptoms and most patient deaths occurred during the second week of illness progression.

Supportive care, including aggressive fluid replacement, is the mainstay of therapy for MVD. Currently, there are no Food and Drug Administration–approved antiviral treatments or vaccines for Marburg virus. Despite their viral similarities, vaccines against Ebola virus have not been shown to be protective against Marburg virus. Marburg virus vaccine development is ongoing, with a few promising candidate vaccines in early phase 1 and 2 clinical trials. In 2022, in response to MVD outbreaks in Ghana and Guinea, the World Health Organization convened an international Marburg virus vaccine consortium which is working to promote global research collaboration for more rapid vaccine development.

In the absence of definitive therapies, early identification of patients with suspected MVD is critical for preventing the spread of infection to close contacts. Like Ebola virus–infected patients, only symptomatic MVD patients are infectious and all patients with suspected MVD should be isolated in a private room and cared for in accordance with infection control procedures. As MVD is a nationally notifiable disease, suspected cases should be reported to local or state health departments as per jurisdictional requirements. Clinicians should also consult with their local or state health department and CDC for guidance on testing patients with suspected MVD and consider prompt evaluation for other infectious etiologies in the patient’s differential diagnosis. Comprehensive guidance for clinicians on screening and diagnosing patients with MVD is available on the CDC website at https://www.cdc.gov/vhf/marburg/index.html.

Dr. Appiah (she/her) is a medical epidemiologist in the division of global migration and quarantine at the CDC. Dr. Appiah holds adjunct faculty appointment in the division of infectious diseases at Emory University, Atlanta. She also holds a commission in the U.S. Public Health Service and is a resident advisor, Uganda, U.S. President’s Malaria Initiative, at the CDC.

What do green monkeys, fruit bats, and python caves all have in common? All have been implicated in outbreaks as transmission sources of the rare but deadly Marburg virus. Marburg virus is in the same Filoviridae family of highly pathogenic RNA viruses as Ebola virus, and similarly can cause a rapidly progressive and fatal viral hemorrhagic fever.

In the first reported Marburg outbreak in 1967, laboratory workers in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia, developed severe febrile illnesses with massive hemorrhage and multiorgan system dysfunction after contact with infected African green monkeys imported from Uganda. Since the first discovery of Marburg virus, there have been over 14 Marburg virus disease (MVD) outbreaks worldwide with nearly 600 cases and case fatality rates of 23%-90%.

The majority of MVD outbreaks have occurred in sub-Saharan Africa, and primarily in three African countries: Angola, the Democratic Republic of Congo, and Uganda. In sub-Saharan Africa, these sporadic outbreaks have had high case fatality rates (up to 80%-90%) and been linked to human exposure to the oral secretions or urinary/fecal droppings of Egyptian fruit bats (Rousettus aegyptiacus), the animal reservoir for Marburg virus. These exposures have primarily occurred among miners or tourists frequenting bat-infested mines or caves, including Uganda’s python cave, where Centers for Disease Control and Prevention investigators have conducted ecological studies on Marburg-infected bats. Person-to-person transmission occurs from direct contact with the blood or bodily fluids of an infected person or contact with a contaminated object (for example, unsterilized needles and syringes in a large nosocomial outbreak in Angola).

On April 6, 2023, the CDC issued a Health Advisory for U.S. clinicians and public health departments regarding two separate MVD outbreaks in Equatorial Guinea and Tanzania. These first-ever MVD outbreaks in both West and East African countries appear to be epidemiologically unrelated. As of March 24, 2023, in Equatorial Guinea, a total of 15 confirmed cases, including 11 deaths, and 23 probable cases, all deceased, have been identified in multiple districts since the outbreak declaration in February 2023. In Tanzania, a total of eight cases, including five deaths, have been reported among villagers in a northwest region since the outbreak declaration in March 2023. While so far cases in the Tanzania MVD outbreak have been epidemiologically linked, in Equatorial Guinea some cases have no identified epidemiological links, raising concern for ongoing community spread.

To date, no cases in these outbreaks have been reported in the United States or outside the affected countries. Overall, the risk of MVD in nonendemic countries, like the United States, is low but there is still a risk of importation. As of May 2, 2023, CDC has issued a Level 2 travel alert (practice enhanced precautions) for Marburg in Equatorial Guinea and a Level 1 travel watch (practice usual precautions) for Marburg in Tanzania. Travelers to these countries are advised to avoid nonessential travel to areas with active outbreaks and practice preventative measures, including avoiding contact with sick people, blood and bodily fluids, dead bodies, fruit bats, and nonhuman primates. International travelers returning to the United States from these countries are advised to self-monitor for Marburg symptoms during travel and for 21 days after country departure. Travelers who develop signs or symptoms of MVD should immediately self-isolate and contact their local health department or clinician.

So, how should clinicians manage such return travelers? In the setting of these new MVD outbreaks in sub-Saharan Africa, what do U.S. clinicians need to know? Clinicians should consider MVD in the differential diagnosis of ill patients with a compatible exposure history and clinical presentation. A detailed exposure history should be obtained to determine if patients have been to an area with an active MVD outbreak during their incubation period (in the past 21 days), had concerning epidemiologic risk factors (for example, presence at funerals, health care facilities, in mines/caves) while in the affected area, and/or had contact with a suspected or confirmed MVD case.

Clinical diagnosis of MVD is challenging as the initial dry symptoms of infection are nonspecific (fever, influenza-like illness, malaise, anorexia, etc.) and can resemble other febrile infectious illnesses. Similarly, presenting alternative or concurrent infections, particularly in febrile return travelers, include malaria, Lassa fever, typhoid, and measles. From these nonspecific symptoms, patients with MVD can then progress to the more severe wet symptoms (for example, vomiting, diarrhea, and bleeding). Common clinical features of MVD have been described based on the clinical presentation and course of cases in MVD outbreaks. Notably, in the original Marburg outbreak, maculopapular rash and conjunctival injection were early patient symptoms and most patient deaths occurred during the second week of illness progression.

Supportive care, including aggressive fluid replacement, is the mainstay of therapy for MVD. Currently, there are no Food and Drug Administration–approved antiviral treatments or vaccines for Marburg virus. Despite their viral similarities, vaccines against Ebola virus have not been shown to be protective against Marburg virus. Marburg virus vaccine development is ongoing, with a few promising candidate vaccines in early phase 1 and 2 clinical trials. In 2022, in response to MVD outbreaks in Ghana and Guinea, the World Health Organization convened an international Marburg virus vaccine consortium which is working to promote global research collaboration for more rapid vaccine development.

In the absence of definitive therapies, early identification of patients with suspected MVD is critical for preventing the spread of infection to close contacts. Like Ebola virus–infected patients, only symptomatic MVD patients are infectious and all patients with suspected MVD should be isolated in a private room and cared for in accordance with infection control procedures. As MVD is a nationally notifiable disease, suspected cases should be reported to local or state health departments as per jurisdictional requirements. Clinicians should also consult with their local or state health department and CDC for guidance on testing patients with suspected MVD and consider prompt evaluation for other infectious etiologies in the patient’s differential diagnosis. Comprehensive guidance for clinicians on screening and diagnosing patients with MVD is available on the CDC website at https://www.cdc.gov/vhf/marburg/index.html.

Dr. Appiah (she/her) is a medical epidemiologist in the division of global migration and quarantine at the CDC. Dr. Appiah holds adjunct faculty appointment in the division of infectious diseases at Emory University, Atlanta. She also holds a commission in the U.S. Public Health Service and is a resident advisor, Uganda, U.S. President’s Malaria Initiative, at the CDC.

What do green monkeys, fruit bats, and python caves all have in common? All have been implicated in outbreaks as transmission sources of the rare but deadly Marburg virus. Marburg virus is in the same Filoviridae family of highly pathogenic RNA viruses as Ebola virus, and similarly can cause a rapidly progressive and fatal viral hemorrhagic fever.

In the first reported Marburg outbreak in 1967, laboratory workers in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia, developed severe febrile illnesses with massive hemorrhage and multiorgan system dysfunction after contact with infected African green monkeys imported from Uganda. Since the first discovery of Marburg virus, there have been over 14 Marburg virus disease (MVD) outbreaks worldwide with nearly 600 cases and case fatality rates of 23%-90%.

The majority of MVD outbreaks have occurred in sub-Saharan Africa, and primarily in three African countries: Angola, the Democratic Republic of Congo, and Uganda. In sub-Saharan Africa, these sporadic outbreaks have had high case fatality rates (up to 80%-90%) and been linked to human exposure to the oral secretions or urinary/fecal droppings of Egyptian fruit bats (Rousettus aegyptiacus), the animal reservoir for Marburg virus. These exposures have primarily occurred among miners or tourists frequenting bat-infested mines or caves, including Uganda’s python cave, where Centers for Disease Control and Prevention investigators have conducted ecological studies on Marburg-infected bats. Person-to-person transmission occurs from direct contact with the blood or bodily fluids of an infected person or contact with a contaminated object (for example, unsterilized needles and syringes in a large nosocomial outbreak in Angola).

On April 6, 2023, the CDC issued a Health Advisory for U.S. clinicians and public health departments regarding two separate MVD outbreaks in Equatorial Guinea and Tanzania. These first-ever MVD outbreaks in both West and East African countries appear to be epidemiologically unrelated. As of March 24, 2023, in Equatorial Guinea, a total of 15 confirmed cases, including 11 deaths, and 23 probable cases, all deceased, have been identified in multiple districts since the outbreak declaration in February 2023. In Tanzania, a total of eight cases, including five deaths, have been reported among villagers in a northwest region since the outbreak declaration in March 2023. While so far cases in the Tanzania MVD outbreak have been epidemiologically linked, in Equatorial Guinea some cases have no identified epidemiological links, raising concern for ongoing community spread.

To date, no cases in these outbreaks have been reported in the United States or outside the affected countries. Overall, the risk of MVD in nonendemic countries, like the United States, is low but there is still a risk of importation. As of May 2, 2023, CDC has issued a Level 2 travel alert (practice enhanced precautions) for Marburg in Equatorial Guinea and a Level 1 travel watch (practice usual precautions) for Marburg in Tanzania. Travelers to these countries are advised to avoid nonessential travel to areas with active outbreaks and practice preventative measures, including avoiding contact with sick people, blood and bodily fluids, dead bodies, fruit bats, and nonhuman primates. International travelers returning to the United States from these countries are advised to self-monitor for Marburg symptoms during travel and for 21 days after country departure. Travelers who develop signs or symptoms of MVD should immediately self-isolate and contact their local health department or clinician.

So, how should clinicians manage such return travelers? In the setting of these new MVD outbreaks in sub-Saharan Africa, what do U.S. clinicians need to know? Clinicians should consider MVD in the differential diagnosis of ill patients with a compatible exposure history and clinical presentation. A detailed exposure history should be obtained to determine if patients have been to an area with an active MVD outbreak during their incubation period (in the past 21 days), had concerning epidemiologic risk factors (for example, presence at funerals, health care facilities, in mines/caves) while in the affected area, and/or had contact with a suspected or confirmed MVD case.

Clinical diagnosis of MVD is challenging as the initial dry symptoms of infection are nonspecific (fever, influenza-like illness, malaise, anorexia, etc.) and can resemble other febrile infectious illnesses. Similarly, presenting alternative or concurrent infections, particularly in febrile return travelers, include malaria, Lassa fever, typhoid, and measles. From these nonspecific symptoms, patients with MVD can then progress to the more severe wet symptoms (for example, vomiting, diarrhea, and bleeding). Common clinical features of MVD have been described based on the clinical presentation and course of cases in MVD outbreaks. Notably, in the original Marburg outbreak, maculopapular rash and conjunctival injection were early patient symptoms and most patient deaths occurred during the second week of illness progression.

Supportive care, including aggressive fluid replacement, is the mainstay of therapy for MVD. Currently, there are no Food and Drug Administration–approved antiviral treatments or vaccines for Marburg virus. Despite their viral similarities, vaccines against Ebola virus have not been shown to be protective against Marburg virus. Marburg virus vaccine development is ongoing, with a few promising candidate vaccines in early phase 1 and 2 clinical trials. In 2022, in response to MVD outbreaks in Ghana and Guinea, the World Health Organization convened an international Marburg virus vaccine consortium which is working to promote global research collaboration for more rapid vaccine development.

In the absence of definitive therapies, early identification of patients with suspected MVD is critical for preventing the spread of infection to close contacts. Like Ebola virus–infected patients, only symptomatic MVD patients are infectious and all patients with suspected MVD should be isolated in a private room and cared for in accordance with infection control procedures. As MVD is a nationally notifiable disease, suspected cases should be reported to local or state health departments as per jurisdictional requirements. Clinicians should also consult with their local or state health department and CDC for guidance on testing patients with suspected MVD and consider prompt evaluation for other infectious etiologies in the patient’s differential diagnosis. Comprehensive guidance for clinicians on screening and diagnosing patients with MVD is available on the CDC website at https://www.cdc.gov/vhf/marburg/index.html.

Dr. Appiah (she/her) is a medical epidemiologist in the division of global migration and quarantine at the CDC. Dr. Appiah holds adjunct faculty appointment in the division of infectious diseases at Emory University, Atlanta. She also holds a commission in the U.S. Public Health Service and is a resident advisor, Uganda, U.S. President’s Malaria Initiative, at the CDC.

There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.

Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.

Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.

In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained. 
 

Claims-based analysis

To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.

They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.

Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.

Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.

For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.

When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.

In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).

Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.

The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.

These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.

A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
 

Underestimated burden

Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”

“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”

“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.

“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added. 

Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.

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

There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.

Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.

Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.

In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained. 
 

Claims-based analysis

To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.

They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.

Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.

Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.

For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.

When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.

In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).

Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.

The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.

These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.

A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
 

Underestimated burden

Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”

“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”

“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.

“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added. 

Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.

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

There has been an increase in the incidence and prevalence of myasthenia gravis in the United States, an analysis of new claims data shows. Investigators speculate the rise of this rare disorder may be due to “increased diagnosis and more awareness of the disease over time, which has been shown in several studies,” study investigator Ema Rodrigues, DSc, MPH, with Alexion Pharmaceuticals, Boston.

Dr. Rodrigues presented her research at the 2023 annual meeting of the American Academy of Neurology.

Myasthenia gravis is a rare neuromuscular disease characterized by muscle weakness and fatigue caused by the binding of autoantibodies at the neuromuscular junction. It affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat, and limbs.

In Europe, the incidence and prevalence of myasthenia gravis has increased for the past several decades. In the United States, increasing prevalence has also been observed, but recent estimates are lacking, making it tough to gauge the true burden of disease, Dr. Rodrigues explained. 
 

Claims-based analysis

To investigate, Dr. Rodrigues and colleagues analyzed claims data (commercial, Medicare, and Medicaid) and electronic health records representing over 300 million patients in the United States from 2011 to present.

They calculated sex- and age-specific incidence and prevalence of myasthenia gravis for the year 2021 using U.S. Census data.

Prevalent patients were identified as having one or more myasthenia gravis records in 2021 and two or more myasthenia gravis records, at least 30 days apart, from 2016 to 2021. This cohort had 78,225 patients.

Incident patients were identified as those with a myasthenia gravis record in 2021 and no previous myasthenia gravis record from 2019 to 2020. This cohort had 4,214 patients.

For both the prevalent and incident cohort, the distribution of male and female patients was roughly 50/50, with a slightly higher proportion of females in the incident cohort, Dr. Rodrigues reported.

When looking at age groups, there were “very few pediatric patients,” she noted, with less than 1% of the patients under the age of 12. The highest proportion of patients were 65 years or older. The mean age was 67 in the prevalent cohort and 68 in the incident cohort.

In 2021, the overall incidence of myasthenia gravis was 3.2 per 100,000 with similar estimates for males and females (3.2 vs. 3.1 per 100,000, respectively).

Total prevalence was estimated to be 37.0 per 100,000 with sex-specific estimates being comparable at 37.3 and 36.7 per 100,000 for males and females, respectively.

The incidence and prevalence of myasthenia gravis increased with age, ranging from 0.3 and 0.4 per 100,000, respectively, in children younger than age 2 years, to 10.2 and 116.8 per 100,000, respectively, in people 65 and older.

These estimates are “significantly higher” than those from a prior U.S. analysis from 2003, Dr. Rodrigues told attendees, but they are quite similar to the estimates that were reported in Sweden in 2020.

A limitation of the analysis is that patients who do not seek care regularly may have not been identified due to inclusion criteria, potentially leading to underestimates. Also, no information was available on the myasthenia gravis subtype (ocular vs. generalized).
 

Underestimated burden

Reached for comment, Richard J. Nowak, MD, MS, director of the Yale Myasthenia Gravis Clinic, Yale School of Medicine, New Haven, Conn., noted that the new report, “albeit limited as a claims-based analysis, presents modern data on incidence and prevalence of myasthenia gravis in the United States.”

“It suggests that the current estimates of myasthenia gravis in the United States are too low and that the true impact/burden of myasthenia gravis is greater. While we are unable to verify the accuracy of the diagnosis, the total myasthenia gravis population is likely to be about 100,000, which is higher than prior estimates.”

“This, in fact, might be driven by greater disease awareness and increased diagnosis along with decreased mortality and longer life expectancy,” Dr. Nowak said.

“Anecdotally, we are most certainly seeing patients with new-onset myasthenia gravis in their 70s, 80s, and even 90s in recent years. The EXPLORE-MG registry published data from a tertiary center on age of onset breakdown showing myasthenia gravis can present at any age,” Dr. Nowak added. 

Funding for the study was provided by Alexion, AstraZeneca Rare Disease. Dr. Rodrigues receives compensation and owns stock as an employee of Alexion, AstraZeneca Rare Diseases. Dr. Nowak has no relevant disclosures.

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

The Food and Drug Administration has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS), the debilitating and deadly disease for which there is no cure.
 

Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.

The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.

While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.

“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”

Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.

The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.

In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles. 

Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.

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

The Food and Drug Administration has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS), the debilitating and deadly disease for which there is no cure.
 

Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.

The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.

While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.

“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”

Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.

The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.

In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles. 

Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.

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

The Food and Drug Administration has approved the first treatment that takes a genetics-based approach to slowing or stopping the progression of a rare form of amyotrophic lateral sclerosis (ALS), the debilitating and deadly disease for which there is no cure.
 

Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.

The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.

While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.

“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”

Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.

The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.

In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles. 

Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.

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

Dercum disease (or adiposis dolorosa) is a rare condition of unknown etiology characterized by multiple painful lipomas localized throughout the body.^1,2 It typically presents in adults aged 35 to 50 years and is at least 5 times more common in women.³ It often is associated with comorbidities such as obesity, fatigue and weakness.¹ There currently are no approved treatments for Dercum disease, only therapies tried with little to no efficacy for symptom management, including analgesics, excision, liposuction,¹ lymphatic drainage,⁴ hypobaric pressure,⁵ and frequency rhythmic electrical modulation systems.⁶ For patients who continually develop widespread lesions, surgical excision is not feasible, which poses a therapeutic challenge. Deoxycholic acid (DCA), a bile acid that is approved to treat submental fat, disrupts the integrity of cell membranes, induces adipocyte lysis, and solubilizes fat when injected subcutaneously.⁷ We used DCA to mitigate pain and reduce lipoma size in patients with Dercum disease, which demonstrated lipoma reduction via ultrasonography in 3 patients.

Case Reports

Three patients presented to clinic with multiple painful subcutaneous nodules throughout several areas of the body and were screened using radiography. Ultrasonography demonstrated numerous lipomas consistent with Dercum disease. The lipomas were measured by ultrasonography to obtain 3-dimensional measurements of each lesion. The most painful lipomas identified by the patients were either treated with 2 mL of DCA (10 mg/mL) or served as a control with no treatment. Patients returned for symptom monitoring and repeat measurements of both treated and untreated lipomas. Two physicians with expertise in ultrasonography measured lesions in a blinded fashion. Photographs were obtained with patient consent.

Patient 1—A 45-year-old woman with a family history of lipomas was diagnosed with Dercum disease that was confirmed via ultrasonography. A painful 1.63×1.64×0.55-cm lipoma was measured on the volar aspect of the left forearm, and a 1.17×1.26×0.39-cm lipoma was measured on the volar aspect of the right wrist. At a follow-up visit 11 months later, 2 mL of DCA was administered to the lipoma on the volar aspect of the left forearm, while the lipoma on the volar aspect of the right wrist was monitored as an untreated control. Following the procedure, the patient reported 1 week of swelling and tenderness of the treated area. Repeat imaging 4 months after administration of DCA revealed reduction of the treated lesion to 0.80×1.48×0.60 cm and growth of the untreated lesion to 1.32×2.17×0.52 cm. The treated lipoma reduced in volume by 34.55%, while the lipoma in the untreated control increased in volume from its original measurement by 111.11% (Table). The patient also reported decreased pain in the treated area at all follow-up visits in the 1 year following the procedure.

Patient 2—A 42-year-old woman with Dercum disease received administration of 2 mL of DCA to a 1.90×1.70×0.90-cm lipoma of the lateral aspect of the left mid thigh and 2 mL of DCA to a 2.40×3.07×0.60-cm lipoma on the volar aspect of the right forearm 2 weeks later. A 1.18×0.91×0.45-cm lipoma of the volar aspect of the left forearm was monitored as an untreated control. The patient reported bruising and discoloration a few weeks following the procedure. At subsequent 1-month and 3-month follow-ups, the patient reported induration in the volar aspect of the right forearm and noticeable reduction in size of the lesion in the lateral aspect of the left mid thigh. At the 6-month follow-up, the patient reported reduction in size of both lesions and improvement of the previously noted side effects. Repeat ultrasonography approximately 6 months after administration of DCA demonstrated reduction of the treated lesion on the lateral aspect of the left mid thigh to 0.92×0.96×0.57 cm and the volar aspect of the right forearm to 1.56×2.18×0.79 cm, with growth of the untreated lesion on the volar aspect of the left forearm to 1.37×1.11×0.39 cm. The treated lipomas reduced in volume by 68.42% and 41.25%, respectively, and the untreated control increased in volume by 22.08% (Table).

Patient 3—A 75-year-old woman with a family history of lipomas was diagnosed with Dercum disease verified by ultrasonography. The patient was administered 2 mL of DCA to a 2.65×3.19×0.71-cm lipoma of the volar aspect of the left forearm. A 1.66×2.02×0.38-cm lipoma of the lateral aspect of the right forearm was monitored as an untreated control. Following the procedure, the patient reported initial swelling that persisted for a few weeks followed by notable pain relief and a decrease in lipoma size. At 2-month follow-up, the patient reported no pain or other adverse effects, while repeat imaging demonstrated reduction of the treated lesion on the volar aspect of the left forearm to 2.13×2.56×0.75 cm and growth of the untreated lesion on the lateral aspect of the right forearm to 1.95×2.05×0.37 cm. The treated lipoma reduced in volume by 30.29%, and the untreated control increased in volume by 15.05% (Table).

Comment

Deoxycholic acid is a bile acid naturally found in the body that helps to emulsify and solubilize fats in the intestines. When injected subcutaneously, DCA becomes an adipolytic agent that induces inflammation and targets adipose degradation by macrophages, and it has been manufactured to reduce submental fat.⁷ Off-label use of DCA has been explored for nonsurgical body contouring and lipomas with promising results in some cases; however, these prior studies have been limited by the lack of quantitative objective measurements to effectively demonstrate the impact of treatment.^8,9

We present 3 patients who requested treatment for numerous painful lipomas. Given the extent of their disease, surgical options were not feasible, and the patients opted to try a nonsurgical alternative. In each case, the painful lipomas that were chosen for treatment were injected with 2 mL of DCA. Injection-associated symptoms included swelling, tenderness, discoloration, and induration, which resolved over a period of months. Patient 1 had a treated lipoma that reduced in volume by approximately 35%, while the control continued to grow and doubled in volume. In patient 2, the treated lesion on the lateral aspect of the mid thigh reduced in volume by almost 70%, and the treated lesion on the volar aspect of the right forearm reduced in volume by more than 40%, while the control grew by more than 20%. In patient 3, the volume of the treated lipoma decreased by 30%, and the control increased by 15%. The follow-up interval was shortest in patient 3—2 months as opposed to 11 months and 6 months for patients 1 and 2, respectively; therefore, more progress may be seen in patient 3 with more time. Interestingly, a change in shape of the lipoma was noted in patient 3 (Figure)—an increase in its depth while the center became anechoic, which is a sign of hollowing in the center due to the saponification of fat and a possible cause for the change from an elliptical to a more spherical or doughnutlike shape. Intralesional administration of DCA may offer patients with extensive lipomas, such as those seen in patients with Dercum disease, an alternative, less-invasive option to assist with pain and tumor burden when excision is not feasible. Although treatments with DCA can be associated with side effects, including pain, swelling, bruising, erythema, induration, and numbness, all 3 of our patients had ultimate mitigation of pain and reduction in lipoma size within months of the injection. Additional studies should be explored to determine the optimal dose and frequency of administration of DCA that could benefit patients with Dercum disease.

Dercum disease (or adiposis dolorosa) is a rare condition of unknown etiology characterized by multiple painful lipomas localized throughout the body.^1,2 It typically presents in adults aged 35 to 50 years and is at least 5 times more common in women.³ It often is associated with comorbidities such as obesity, fatigue and weakness.¹ There currently are no approved treatments for Dercum disease, only therapies tried with little to no efficacy for symptom management, including analgesics, excision, liposuction,¹ lymphatic drainage,⁴ hypobaric pressure,⁵ and frequency rhythmic electrical modulation systems.⁶ For patients who continually develop widespread lesions, surgical excision is not feasible, which poses a therapeutic challenge. Deoxycholic acid (DCA), a bile acid that is approved to treat submental fat, disrupts the integrity of cell membranes, induces adipocyte lysis, and solubilizes fat when injected subcutaneously.⁷ We used DCA to mitigate pain and reduce lipoma size in patients with Dercum disease, which demonstrated lipoma reduction via ultrasonography in 3 patients.

Case Reports

Three patients presented to clinic with multiple painful subcutaneous nodules throughout several areas of the body and were screened using radiography. Ultrasonography demonstrated numerous lipomas consistent with Dercum disease. The lipomas were measured by ultrasonography to obtain 3-dimensional measurements of each lesion. The most painful lipomas identified by the patients were either treated with 2 mL of DCA (10 mg/mL) or served as a control with no treatment. Patients returned for symptom monitoring and repeat measurements of both treated and untreated lipomas. Two physicians with expertise in ultrasonography measured lesions in a blinded fashion. Photographs were obtained with patient consent.

Patient 1—A 45-year-old woman with a family history of lipomas was diagnosed with Dercum disease that was confirmed via ultrasonography. A painful 1.63×1.64×0.55-cm lipoma was measured on the volar aspect of the left forearm, and a 1.17×1.26×0.39-cm lipoma was measured on the volar aspect of the right wrist. At a follow-up visit 11 months later, 2 mL of DCA was administered to the lipoma on the volar aspect of the left forearm, while the lipoma on the volar aspect of the right wrist was monitored as an untreated control. Following the procedure, the patient reported 1 week of swelling and tenderness of the treated area. Repeat imaging 4 months after administration of DCA revealed reduction of the treated lesion to 0.80×1.48×0.60 cm and growth of the untreated lesion to 1.32×2.17×0.52 cm. The treated lipoma reduced in volume by 34.55%, while the lipoma in the untreated control increased in volume from its original measurement by 111.11% (Table). The patient also reported decreased pain in the treated area at all follow-up visits in the 1 year following the procedure.

Patient 2—A 42-year-old woman with Dercum disease received administration of 2 mL of DCA to a 1.90×1.70×0.90-cm lipoma of the lateral aspect of the left mid thigh and 2 mL of DCA to a 2.40×3.07×0.60-cm lipoma on the volar aspect of the right forearm 2 weeks later. A 1.18×0.91×0.45-cm lipoma of the volar aspect of the left forearm was monitored as an untreated control. The patient reported bruising and discoloration a few weeks following the procedure. At subsequent 1-month and 3-month follow-ups, the patient reported induration in the volar aspect of the right forearm and noticeable reduction in size of the lesion in the lateral aspect of the left mid thigh. At the 6-month follow-up, the patient reported reduction in size of both lesions and improvement of the previously noted side effects. Repeat ultrasonography approximately 6 months after administration of DCA demonstrated reduction of the treated lesion on the lateral aspect of the left mid thigh to 0.92×0.96×0.57 cm and the volar aspect of the right forearm to 1.56×2.18×0.79 cm, with growth of the untreated lesion on the volar aspect of the left forearm to 1.37×1.11×0.39 cm. The treated lipomas reduced in volume by 68.42% and 41.25%, respectively, and the untreated control increased in volume by 22.08% (Table).

Patient 3—A 75-year-old woman with a family history of lipomas was diagnosed with Dercum disease verified by ultrasonography. The patient was administered 2 mL of DCA to a 2.65×3.19×0.71-cm lipoma of the volar aspect of the left forearm. A 1.66×2.02×0.38-cm lipoma of the lateral aspect of the right forearm was monitored as an untreated control. Following the procedure, the patient reported initial swelling that persisted for a few weeks followed by notable pain relief and a decrease in lipoma size. At 2-month follow-up, the patient reported no pain or other adverse effects, while repeat imaging demonstrated reduction of the treated lesion on the volar aspect of the left forearm to 2.13×2.56×0.75 cm and growth of the untreated lesion on the lateral aspect of the right forearm to 1.95×2.05×0.37 cm. The treated lipoma reduced in volume by 30.29%, and the untreated control increased in volume by 15.05% (Table).

Comment

Deoxycholic acid is a bile acid naturally found in the body that helps to emulsify and solubilize fats in the intestines. When injected subcutaneously, DCA becomes an adipolytic agent that induces inflammation and targets adipose degradation by macrophages, and it has been manufactured to reduce submental fat.⁷ Off-label use of DCA has been explored for nonsurgical body contouring and lipomas with promising results in some cases; however, these prior studies have been limited by the lack of quantitative objective measurements to effectively demonstrate the impact of treatment.^8,9

We present 3 patients who requested treatment for numerous painful lipomas. Given the extent of their disease, surgical options were not feasible, and the patients opted to try a nonsurgical alternative. In each case, the painful lipomas that were chosen for treatment were injected with 2 mL of DCA. Injection-associated symptoms included swelling, tenderness, discoloration, and induration, which resolved over a period of months. Patient 1 had a treated lipoma that reduced in volume by approximately 35%, while the control continued to grow and doubled in volume. In patient 2, the treated lesion on the lateral aspect of the mid thigh reduced in volume by almost 70%, and the treated lesion on the volar aspect of the right forearm reduced in volume by more than 40%, while the control grew by more than 20%. In patient 3, the volume of the treated lipoma decreased by 30%, and the control increased by 15%. The follow-up interval was shortest in patient 3—2 months as opposed to 11 months and 6 months for patients 1 and 2, respectively; therefore, more progress may be seen in patient 3 with more time. Interestingly, a change in shape of the lipoma was noted in patient 3 (Figure)—an increase in its depth while the center became anechoic, which is a sign of hollowing in the center due to the saponification of fat and a possible cause for the change from an elliptical to a more spherical or doughnutlike shape. Intralesional administration of DCA may offer patients with extensive lipomas, such as those seen in patients with Dercum disease, an alternative, less-invasive option to assist with pain and tumor burden when excision is not feasible. Although treatments with DCA can be associated with side effects, including pain, swelling, bruising, erythema, induration, and numbness, all 3 of our patients had ultimate mitigation of pain and reduction in lipoma size within months of the injection. Additional studies should be explored to determine the optimal dose and frequency of administration of DCA that could benefit patients with Dercum disease.

Dercum disease (or adiposis dolorosa) is a rare condition of unknown etiology characterized by multiple painful lipomas localized throughout the body.^1,2 It typically presents in adults aged 35 to 50 years and is at least 5 times more common in women.³ It often is associated with comorbidities such as obesity, fatigue and weakness.¹ There currently are no approved treatments for Dercum disease, only therapies tried with little to no efficacy for symptom management, including analgesics, excision, liposuction,¹ lymphatic drainage,⁴ hypobaric pressure,⁵ and frequency rhythmic electrical modulation systems.⁶ For patients who continually develop widespread lesions, surgical excision is not feasible, which poses a therapeutic challenge. Deoxycholic acid (DCA), a bile acid that is approved to treat submental fat, disrupts the integrity of cell membranes, induces adipocyte lysis, and solubilizes fat when injected subcutaneously.⁷ We used DCA to mitigate pain and reduce lipoma size in patients with Dercum disease, which demonstrated lipoma reduction via ultrasonography in 3 patients.

Case Reports

Three patients presented to clinic with multiple painful subcutaneous nodules throughout several areas of the body and were screened using radiography. Ultrasonography demonstrated numerous lipomas consistent with Dercum disease. The lipomas were measured by ultrasonography to obtain 3-dimensional measurements of each lesion. The most painful lipomas identified by the patients were either treated with 2 mL of DCA (10 mg/mL) or served as a control with no treatment. Patients returned for symptom monitoring and repeat measurements of both treated and untreated lipomas. Two physicians with expertise in ultrasonography measured lesions in a blinded fashion. Photographs were obtained with patient consent.

Patient 1—A 45-year-old woman with a family history of lipomas was diagnosed with Dercum disease that was confirmed via ultrasonography. A painful 1.63×1.64×0.55-cm lipoma was measured on the volar aspect of the left forearm, and a 1.17×1.26×0.39-cm lipoma was measured on the volar aspect of the right wrist. At a follow-up visit 11 months later, 2 mL of DCA was administered to the lipoma on the volar aspect of the left forearm, while the lipoma on the volar aspect of the right wrist was monitored as an untreated control. Following the procedure, the patient reported 1 week of swelling and tenderness of the treated area. Repeat imaging 4 months after administration of DCA revealed reduction of the treated lesion to 0.80×1.48×0.60 cm and growth of the untreated lesion to 1.32×2.17×0.52 cm. The treated lipoma reduced in volume by 34.55%, while the lipoma in the untreated control increased in volume from its original measurement by 111.11% (Table). The patient also reported decreased pain in the treated area at all follow-up visits in the 1 year following the procedure.

Patient 2—A 42-year-old woman with Dercum disease received administration of 2 mL of DCA to a 1.90×1.70×0.90-cm lipoma of the lateral aspect of the left mid thigh and 2 mL of DCA to a 2.40×3.07×0.60-cm lipoma on the volar aspect of the right forearm 2 weeks later. A 1.18×0.91×0.45-cm lipoma of the volar aspect of the left forearm was monitored as an untreated control. The patient reported bruising and discoloration a few weeks following the procedure. At subsequent 1-month and 3-month follow-ups, the patient reported induration in the volar aspect of the right forearm and noticeable reduction in size of the lesion in the lateral aspect of the left mid thigh. At the 6-month follow-up, the patient reported reduction in size of both lesions and improvement of the previously noted side effects. Repeat ultrasonography approximately 6 months after administration of DCA demonstrated reduction of the treated lesion on the lateral aspect of the left mid thigh to 0.92×0.96×0.57 cm and the volar aspect of the right forearm to 1.56×2.18×0.79 cm, with growth of the untreated lesion on the volar aspect of the left forearm to 1.37×1.11×0.39 cm. The treated lipomas reduced in volume by 68.42% and 41.25%, respectively, and the untreated control increased in volume by 22.08% (Table).

Patient 3—A 75-year-old woman with a family history of lipomas was diagnosed with Dercum disease verified by ultrasonography. The patient was administered 2 mL of DCA to a 2.65×3.19×0.71-cm lipoma of the volar aspect of the left forearm. A 1.66×2.02×0.38-cm lipoma of the lateral aspect of the right forearm was monitored as an untreated control. Following the procedure, the patient reported initial swelling that persisted for a few weeks followed by notable pain relief and a decrease in lipoma size. At 2-month follow-up, the patient reported no pain or other adverse effects, while repeat imaging demonstrated reduction of the treated lesion on the volar aspect of the left forearm to 2.13×2.56×0.75 cm and growth of the untreated lesion on the lateral aspect of the right forearm to 1.95×2.05×0.37 cm. The treated lipoma reduced in volume by 30.29%, and the untreated control increased in volume by 15.05% (Table).

Comment

Deoxycholic acid is a bile acid naturally found in the body that helps to emulsify and solubilize fats in the intestines. When injected subcutaneously, DCA becomes an adipolytic agent that induces inflammation and targets adipose degradation by macrophages, and it has been manufactured to reduce submental fat.⁷ Off-label use of DCA has been explored for nonsurgical body contouring and lipomas with promising results in some cases; however, these prior studies have been limited by the lack of quantitative objective measurements to effectively demonstrate the impact of treatment.^8,9

We present 3 patients who requested treatment for numerous painful lipomas. Given the extent of their disease, surgical options were not feasible, and the patients opted to try a nonsurgical alternative. In each case, the painful lipomas that were chosen for treatment were injected with 2 mL of DCA. Injection-associated symptoms included swelling, tenderness, discoloration, and induration, which resolved over a period of months. Patient 1 had a treated lipoma that reduced in volume by approximately 35%, while the control continued to grow and doubled in volume. In patient 2, the treated lesion on the lateral aspect of the mid thigh reduced in volume by almost 70%, and the treated lesion on the volar aspect of the right forearm reduced in volume by more than 40%, while the control grew by more than 20%. In patient 3, the volume of the treated lipoma decreased by 30%, and the control increased by 15%. The follow-up interval was shortest in patient 3—2 months as opposed to 11 months and 6 months for patients 1 and 2, respectively; therefore, more progress may be seen in patient 3 with more time. Interestingly, a change in shape of the lipoma was noted in patient 3 (Figure)—an increase in its depth while the center became anechoic, which is a sign of hollowing in the center due to the saponification of fat and a possible cause for the change from an elliptical to a more spherical or doughnutlike shape. Intralesional administration of DCA may offer patients with extensive lipomas, such as those seen in patients with Dercum disease, an alternative, less-invasive option to assist with pain and tumor burden when excision is not feasible. Although treatments with DCA can be associated with side effects, including pain, swelling, bruising, erythema, induration, and numbness, all 3 of our patients had ultimate mitigation of pain and reduction in lipoma size within months of the injection. Additional studies should be explored to determine the optimal dose and frequency of administration of DCA that could benefit patients with Dercum disease.