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Know the 15% rule in scleroderma
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
MAUI, HAWAII – The 15% rule in scleroderma is a handy tool that raises awareness of the disease’s associated prevalence of various severe organ complications so clinicians can screen appropriately, Janet Pope, MD, said at the 2020 Rheumatology Winter Clinical Symposium.
Dr. Pope and colleagues in the Canadian Scleroderma Research Group developed the 15% rule because they recognized that scleroderma is rare enough that most physicians practicing outside of a few specialized centers don’t see many affected patients. The systemic autoimmune disease is marked by numerous possible expressions of vascular inflammation and malfunction, fibrosis, and autoimmunity in different organ systems.
“A lot of clinicians do not know how common this stuff is,” according to Dr. Pope, professor of medicine at the University of Western Ontario and head of the division of rheumatology at St. Joseph’s Health Center in London, Ont.
Basically, the 15% rule holds that, at any given time, a patient with scleroderma has roughly a 15% chance – or one in six – of having any of an extensive array of severe organ complications. That means a 15% chance of having prevalent clinically significant pulmonary hypertension as defined by a systolic pulmonary artery pressure of 45 mm Hg or more on Doppler echocardiography, a 15% likelihood of interstitial lung disease or clinically significant pulmonary fibrosis as suggested by a forced vital capacity less than 70% of predicted, a 15% prevalence of Sjögren’s syndrome, a 15% likelihood of having pulmonary artery hypertension upon right heart catheterization, a 15% chance of inflammatory arthritis, and a one-in-six chance of having a myopathy or myositis. Also, diastolic dysfunction, 15%. Ditto symptomatic arrhythmias.
“It’s a good little rule of thumb,” Dr. Pope commented.
The odds of having a current digital ulcer on any given day? Again, about 15%. In addition, scleroderma patients have a 15% lifetime risk of developing a complicated digital ulcer requiring hospitalization and/or amputation, she continued.
And while the prevalence of scleroderma renal crisis in the overall population with scleroderma is low, at 3%, in the subgroup with diffuse cutaneous systemic sclerosis, it climbs to 12%-15%.
Every rule has its exceptions. The 15% rule doesn’t apply to Raynaud’s phenomenon, which is present in nearly all patients with scleroderma, nor to gastroesophageal reflux disease or dysphagia, present in roughly 80% of patients.
Dr. Pope and coinvestigators developed the 15% rule pertaining to the prevalence of serious organ complications in scleroderma by conducting a systematic review of 69 published studies, each including a minimum of 50 scleroderma patients. The detailed results of the systematic review have been published.
Dr. Pope reported receiving research grants from and/or serving as a consultant to more than a dozen pharmaceutical companies.
REPORTING FROM RWCS 2020
New guideline offers recommendations for reproductive health in patients with rheumatic diseases
A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).
“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.
To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.
In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”
“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.
“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
Contraception
In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.
For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
Assisted reproductive technology
In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.
For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
Fertility preservation
In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.
Hormone therapy
In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.
Pregnancy assessment and management
Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.
For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”
Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily
For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.
For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.
Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.
Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.
The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.
The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.
The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.
SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.
A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).
“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.
To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.
In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”
“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.
“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
Contraception
In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.
For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
Assisted reproductive technology
In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.
For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
Fertility preservation
In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.
Hormone therapy
In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.
Pregnancy assessment and management
Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.
For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”
Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily
For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.
For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.
Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.
Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.
The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.
The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.
The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.
SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.
A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).
“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.
To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.
In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”
“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.
“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
Contraception
In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.
For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
Assisted reproductive technology
In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.
For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
Fertility preservation
In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.
Hormone therapy
In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.
Pregnancy assessment and management
Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.
For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”
Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily
For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.
For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.
Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.
Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.
The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.
The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.
The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.
SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.
FROM ARTHRITIS & RHEUMATOLOGY
Meta-analysis eyes impact of adherence to HCQ among SLE patients
Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.
Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.
“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”
For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.
The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.
In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”
Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A1C.’ ”
She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.
In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”
The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.
SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.
Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.
Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.
“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”
For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.
The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.
In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”
Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A1C.’ ”
She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.
In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”
The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.
SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.
Low serum levels of hydroxychloroquine (HCQ) among patients with systemic lupus erythematosus are associated with a threefold increased likelihood of physician- and patient-reported nonadherence to the medication. In addition, routine monitoring of HCQ levels are associated with improvements in adherence and disease activity.
Those are two key findings from a systematic review and meta-analysis published in Arthritis Care & Research.
“HCQ is recommended for all patients with systemic lupus erythematosus (SLE, or lupus) to reduce disease activity and improve damage-free-survival,” the authors, led by Shivani Garg, MD, of the University of Wisconsin–Madison, wrote in the article. “Yet, up to 83% of lupus patients are nonadherent to HCQ commonly because of poor understanding of benefits of HCQ, lack of motivation to continue therapy, and inflated concerns regarding side effects from HCQ use.”
For their analysis, the researchers drew from 17 published observational and interventional studies that measured HCQ levels and assessed adherence or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in adults with SLE. They used forest plots to compare pooled estimates of correlations between HCQ levels and reported nonadherence, or SLEDAI scores. Patient-reported nonadherence was defined as less than 80% medication adherence reported, and physician-reported adherence was estimated based on physicians’ interpretations of the previous month’s adherence as reported by patients during clinic visits.
The study population consisted of 1,223 patients. Dr. Garg and colleagues found a threefold higher odds of reported nonadherence in patients with low HCQ levels (odds ratio, 2.95; P less than .001). The mean SLEDAI score was 3.14 points higher in a group with below-threshold HCQ levels on a priori analysis (P = .053), and 1.4 points higher in a group with HCQ levels below 500 ng/mL (P = .039). Among all patients, those with HCQ levels 750 ng/mL or greater had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower. “Our study support levels greater than or equal to 750 ng/mL to be clinically meaningful and statistically significant to identify disease flare (change in SLEDAI greater than or equal to 3 points) and predict active disease (SLEDAI greater than or equal to 6),” the authors wrote.
In an interview, Michelle A. Petri, MD, MPH, took issue with the HCQ goal of 750 ng/mL or greater recommended by the authors. “I think that was premature,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “We presented data at last year’s ACR [which showed] that the level needs to be higher than that to prevent thrombosis. But it is important to open the discussion that HCQ blood levels are not just for nonadherence. I believe they will help us to reduce retinopathy, and also to make sure the dose remains in an efficacious range, such as what is needed to prevent thrombosis.”
Dr. Petri, who also directs the Hopkins Lupus Center, said that the study’s overall conclusions confirms the need for blood testing for HCQ to identify nonadherence. “Everyone remembers the saying of the [former] Surgeon General Dr. C. Everett Koop: ‘Drugs can’t work if patients don’t take them!’ – in particular, blood levels which represent what the patient has taken in the last month. I call blood levels the ‘lupus A1C.’ ”
She added that HCQ blood levels have utility for nonadherence, prediction of retinopathy, and prevention of thrombosis. Such tests “are now much more widely available, including by some large national laboratories such as Quest Diagnostics, as well as by Exagen. No more excuses.” LabCorp plans to start offering HCQ blood level testing by the middle of 2020, she said.
In their manuscript, the study authors acknowledged certain limitations of their analysis, including the fact that there were only four studies that measured HCQ levels and nonadherence or SLEDAI. “Second, most of the studies that examined the correlation between reported adherence and HCQ blood levels were performed in Europe, and there was only one small U.S. study,” they wrote. “Therefore, generalizability for our findings could be limited because of differences in cultural beliefs, social issues, and insurance/medical coverage in populations from diverse countries.”
The study authors reported having no disclosures. Dr. Petri disclosed that she has conducted research on HCQ that was funded by the National Institutes of Health. She has also conducted research for Exagen.
SOURCE: Garg S et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24155.
FROM ARTHRITIS CARE & RESEARCH
Hypertensive disorders of pregnancy in SLE contribute to later CV outcomes
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.
“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.
To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.
During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.
The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”
HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.
Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.
SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.
FROM ARTHRITIS CARE & RESEARCH
Antimalarial adherence is important for diabetes prevention in lupus
Adhering to antimalarial treatment offers some protection to patients with systemic lupus erythematosus (SLE) from developing type 2 diabetes mellitus (T2DM), according to new research.
Patients who took at least 90% of their prescribed antimalarial doses were 39% less likely to develop T2DM than patients who discontinued antimalarial therapy. Patients who took less than 90% of their prescribed doses but didn’t discontinue treatment were 22% less likely to develop T2DM.
“[O]ur study provides further support for the importance of adherence to antimalarials in SLE by demonstrating protective impacts on T2DM,” Shahrzad Salmasi, PhD, of the University of British Columbia, Vancouver, and colleagues wrote in Arthritis Care & Research.
Dr. Salmasi and colleagues conducted this retrospective study using administrative health data on patients in British Columbia. The researchers analyzed 1,498 patients with SLE. Their mean age was about 44 years, and 91% were women.
The researchers used data on prescription dates and days’ supply to establish antimalarial drug courses and gaps in treatment. A new treatment course occurred when a 90-day gap was exceeded between refills. The researchers calculated the proportion of days covered (PDC) – the total number of days with antimalarials divided by the length of the course – and separated patients into three categories:
- Adherent to treatment – PDC of 0.90 or greater
- Nonadherent – PDC greater than 0 but less than 0.90
- Discontinuer – PDC of 0
The patients had a mean of about 23 antimalarial prescriptions and a mean of about two courses. The mean course duration was 554 days.
At a median follow-up of 4.6 years, there were 140 incident cases of T2DM. The researchers calculated the risk of T2DM among adherent and nonadherent patients, comparing these groups with the discontinuers and adjusting for age, sex, comorbidities, and concomitant medications.
The adjusted hazard ratio for developing T2DM was 0.61 among adherent patients and 0.78 among nonadherent patients.
“This population-based study highlighted that taking less than 90% of the prescribed antimalarials compromises their effect in preventing T2DM in SLE patients,” Dr. Salmasi and colleagues wrote. “Our findings should be used to emphasize the importance of medication adherence in not only treating SLE but also preventing its complications.”
The researchers reported having no conflicts of interest.
SOURCE: Salmasi S et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24147.
Adhering to antimalarial treatment offers some protection to patients with systemic lupus erythematosus (SLE) from developing type 2 diabetes mellitus (T2DM), according to new research.
Patients who took at least 90% of their prescribed antimalarial doses were 39% less likely to develop T2DM than patients who discontinued antimalarial therapy. Patients who took less than 90% of their prescribed doses but didn’t discontinue treatment were 22% less likely to develop T2DM.
“[O]ur study provides further support for the importance of adherence to antimalarials in SLE by demonstrating protective impacts on T2DM,” Shahrzad Salmasi, PhD, of the University of British Columbia, Vancouver, and colleagues wrote in Arthritis Care & Research.
Dr. Salmasi and colleagues conducted this retrospective study using administrative health data on patients in British Columbia. The researchers analyzed 1,498 patients with SLE. Their mean age was about 44 years, and 91% were women.
The researchers used data on prescription dates and days’ supply to establish antimalarial drug courses and gaps in treatment. A new treatment course occurred when a 90-day gap was exceeded between refills. The researchers calculated the proportion of days covered (PDC) – the total number of days with antimalarials divided by the length of the course – and separated patients into three categories:
- Adherent to treatment – PDC of 0.90 or greater
- Nonadherent – PDC greater than 0 but less than 0.90
- Discontinuer – PDC of 0
The patients had a mean of about 23 antimalarial prescriptions and a mean of about two courses. The mean course duration was 554 days.
At a median follow-up of 4.6 years, there were 140 incident cases of T2DM. The researchers calculated the risk of T2DM among adherent and nonadherent patients, comparing these groups with the discontinuers and adjusting for age, sex, comorbidities, and concomitant medications.
The adjusted hazard ratio for developing T2DM was 0.61 among adherent patients and 0.78 among nonadherent patients.
“This population-based study highlighted that taking less than 90% of the prescribed antimalarials compromises their effect in preventing T2DM in SLE patients,” Dr. Salmasi and colleagues wrote. “Our findings should be used to emphasize the importance of medication adherence in not only treating SLE but also preventing its complications.”
The researchers reported having no conflicts of interest.
SOURCE: Salmasi S et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24147.
Adhering to antimalarial treatment offers some protection to patients with systemic lupus erythematosus (SLE) from developing type 2 diabetes mellitus (T2DM), according to new research.
Patients who took at least 90% of their prescribed antimalarial doses were 39% less likely to develop T2DM than patients who discontinued antimalarial therapy. Patients who took less than 90% of their prescribed doses but didn’t discontinue treatment were 22% less likely to develop T2DM.
“[O]ur study provides further support for the importance of adherence to antimalarials in SLE by demonstrating protective impacts on T2DM,” Shahrzad Salmasi, PhD, of the University of British Columbia, Vancouver, and colleagues wrote in Arthritis Care & Research.
Dr. Salmasi and colleagues conducted this retrospective study using administrative health data on patients in British Columbia. The researchers analyzed 1,498 patients with SLE. Their mean age was about 44 years, and 91% were women.
The researchers used data on prescription dates and days’ supply to establish antimalarial drug courses and gaps in treatment. A new treatment course occurred when a 90-day gap was exceeded between refills. The researchers calculated the proportion of days covered (PDC) – the total number of days with antimalarials divided by the length of the course – and separated patients into three categories:
- Adherent to treatment – PDC of 0.90 or greater
- Nonadherent – PDC greater than 0 but less than 0.90
- Discontinuer – PDC of 0
The patients had a mean of about 23 antimalarial prescriptions and a mean of about two courses. The mean course duration was 554 days.
At a median follow-up of 4.6 years, there were 140 incident cases of T2DM. The researchers calculated the risk of T2DM among adherent and nonadherent patients, comparing these groups with the discontinuers and adjusting for age, sex, comorbidities, and concomitant medications.
The adjusted hazard ratio for developing T2DM was 0.61 among adherent patients and 0.78 among nonadherent patients.
“This population-based study highlighted that taking less than 90% of the prescribed antimalarials compromises their effect in preventing T2DM in SLE patients,” Dr. Salmasi and colleagues wrote. “Our findings should be used to emphasize the importance of medication adherence in not only treating SLE but also preventing its complications.”
The researchers reported having no conflicts of interest.
SOURCE: Salmasi S et al. Arthritis Care Res. 2020 Jan 21. doi: 10.1002/acr.24147.
FROM ARTHRITIS CARE & RESEARCH
February 2020
Subacute cutaneous lupus erythematosus
Subacute cutaneous lupus erythematosus (SCLE) is a type of cutaneous lupus erythematosus that may occur independently of or in combination with systemic lupus erythematosus. About 10%-15% of patients with SCLE will develop systemic lupus erythematosus. White females are more typically affected.
SCLE lesions often present as scaly, annular, or polycyclic scaly patches and plaques with central clearing. They may appear psoriasiform. They heal without atrophy or scarring but may leave dyspigmentation. Follicular plugging is absent. Lesions generally occur on sun exposed areas such as the neck, V of the chest, and upper extremities. Up to 75% of patients may exhibit associated symptoms such as photosensitivity, oral ulcers, and arthritis. Less than 20% of patients will develop internal disease, including nephritis and pulmonary disease. Symptoms of Sjögren’s syndrome and SCLE may overlap in some patients, and will portend higher risk for internal disease.
The differential diagnosis includes eczema, psoriasis, dermatophytosis, granuloma annulare, and erythema annulare centrifugum. Histology reveals epidermal atrophy and keratinocyte apoptosis, with a superficial and perivascular lymphohistiocytic infiltrate in the upper dermis. Interface changes at the dermal-epidermal junction can be seen. Direct immunofluorescence of lesional skin is positive in one-third of cases, often revealing granular deposits of IgG and IgM at the dermal-epidermal junction and around hair follicles (called the lupus-band test). Serology in SCLE may reveal a positive antinuclear antigen test, as well as positive Ro/SSA antigen. Other lupus serologies such as La/SSB, dsDNA, antihistone, and Sm antibodies may be positive, but are less commonly seen.
Several drugs may cause SCLE, such as hydrochlorothiazide, terbinafine, ACE inhibitors, NSAIDs, calcium-channel blockers, interferons, anticonvulsants, griseofulvin, penicillamine, spironolactone, tumor necrosis factor–alpha inhibitors, and statins. Discontinuing the offending medications may clear the lesions, but not always.
Treatment includes sunscreen and avoidance of sun exposure. Potent topical corticosteroids are helpful. If systemic treatment is indicated, antimalarials are first line.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Subacute cutaneous lupus erythematosus
Subacute cutaneous lupus erythematosus (SCLE) is a type of cutaneous lupus erythematosus that may occur independently of or in combination with systemic lupus erythematosus. About 10%-15% of patients with SCLE will develop systemic lupus erythematosus. White females are more typically affected.
SCLE lesions often present as scaly, annular, or polycyclic scaly patches and plaques with central clearing. They may appear psoriasiform. They heal without atrophy or scarring but may leave dyspigmentation. Follicular plugging is absent. Lesions generally occur on sun exposed areas such as the neck, V of the chest, and upper extremities. Up to 75% of patients may exhibit associated symptoms such as photosensitivity, oral ulcers, and arthritis. Less than 20% of patients will develop internal disease, including nephritis and pulmonary disease. Symptoms of Sjögren’s syndrome and SCLE may overlap in some patients, and will portend higher risk for internal disease.
The differential diagnosis includes eczema, psoriasis, dermatophytosis, granuloma annulare, and erythema annulare centrifugum. Histology reveals epidermal atrophy and keratinocyte apoptosis, with a superficial and perivascular lymphohistiocytic infiltrate in the upper dermis. Interface changes at the dermal-epidermal junction can be seen. Direct immunofluorescence of lesional skin is positive in one-third of cases, often revealing granular deposits of IgG and IgM at the dermal-epidermal junction and around hair follicles (called the lupus-band test). Serology in SCLE may reveal a positive antinuclear antigen test, as well as positive Ro/SSA antigen. Other lupus serologies such as La/SSB, dsDNA, antihistone, and Sm antibodies may be positive, but are less commonly seen.
Several drugs may cause SCLE, such as hydrochlorothiazide, terbinafine, ACE inhibitors, NSAIDs, calcium-channel blockers, interferons, anticonvulsants, griseofulvin, penicillamine, spironolactone, tumor necrosis factor–alpha inhibitors, and statins. Discontinuing the offending medications may clear the lesions, but not always.
Treatment includes sunscreen and avoidance of sun exposure. Potent topical corticosteroids are helpful. If systemic treatment is indicated, antimalarials are first line.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Subacute cutaneous lupus erythematosus
Subacute cutaneous lupus erythematosus (SCLE) is a type of cutaneous lupus erythematosus that may occur independently of or in combination with systemic lupus erythematosus. About 10%-15% of patients with SCLE will develop systemic lupus erythematosus. White females are more typically affected.
SCLE lesions often present as scaly, annular, or polycyclic scaly patches and plaques with central clearing. They may appear psoriasiform. They heal without atrophy or scarring but may leave dyspigmentation. Follicular plugging is absent. Lesions generally occur on sun exposed areas such as the neck, V of the chest, and upper extremities. Up to 75% of patients may exhibit associated symptoms such as photosensitivity, oral ulcers, and arthritis. Less than 20% of patients will develop internal disease, including nephritis and pulmonary disease. Symptoms of Sjögren’s syndrome and SCLE may overlap in some patients, and will portend higher risk for internal disease.
The differential diagnosis includes eczema, psoriasis, dermatophytosis, granuloma annulare, and erythema annulare centrifugum. Histology reveals epidermal atrophy and keratinocyte apoptosis, with a superficial and perivascular lymphohistiocytic infiltrate in the upper dermis. Interface changes at the dermal-epidermal junction can be seen. Direct immunofluorescence of lesional skin is positive in one-third of cases, often revealing granular deposits of IgG and IgM at the dermal-epidermal junction and around hair follicles (called the lupus-band test). Serology in SCLE may reveal a positive antinuclear antigen test, as well as positive Ro/SSA antigen. Other lupus serologies such as La/SSB, dsDNA, antihistone, and Sm antibodies may be positive, but are less commonly seen.
Several drugs may cause SCLE, such as hydrochlorothiazide, terbinafine, ACE inhibitors, NSAIDs, calcium-channel blockers, interferons, anticonvulsants, griseofulvin, penicillamine, spironolactone, tumor necrosis factor–alpha inhibitors, and statins. Discontinuing the offending medications may clear the lesions, but not always.
Treatment includes sunscreen and avoidance of sun exposure. Potent topical corticosteroids are helpful. If systemic treatment is indicated, antimalarials are first line.
This case and photo were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Big data breaks down Sjögren’s syndrome
The severity of Sjögren’s syndrome and its organ involvement has direct links to clinical characteristics that include age, gender, ethnicity, and geographical location, according to new research findings from a large, worldwide database of primary Sjögren’s syndrome patients.
Risk factors for more severe disease included male sex, earlier age at diagnosis, black/African-American (BAA) ethnicity, and living in more southerly countries, including below the equator. The authors hailed these factors as potentially helping to predict the presence of systemic disease in newly-diagnosed patients, as well as helping to determine the optimum follow-up strategy.
But not everyone agrees. In interviews, other experts suggested that the data were interesting and valuable, but were not ready to make reliable clinical predictions. “The predictive value of these data are limited when it comes to an individual patient sitting in front of you in the office,” said Tomas Mustelin, MD, professor of medicine at the University of Washington, Seattle.
“It would be an important clinical thing if you can figure out who’s at risk for systemic complications and who isn’t. This is a nice step in that direction,” said Hal Scofield, MD, professor of medicine and pathology at the University of Oklahoma, Oklahoma City, agreeing that the data were too preliminary to be broadly useful because there is too much overlap between different patient groups.
If there is one clinical message, it is that physicians should be looking beyond dry eyes and dry mouth in newly diagnosed Sjögren’s syndrome, according to Sarah Chung, MD, who is an acting instructor of rheumatology at the University of Washington. “It’s a reminder to investigate these extra-glandular manifestations, and a reminder that it is a heterogeneous presentation, so we have to keep an open mind and investigate thoroughly,” she said.
In the research published online in Rheumatology, first author Pilar Brito-Zerón, MD, PhD, of the University of Barcelona Hospital Clínic, and colleagues in the Sjögren Big Data Consortium used European League Against Rheumatism Sjögren’s syndrome disease activity index (ESSDAI) scores to examine phenotype and patient characteristics among 10,007 subjects drawn from the international consortium.
Overall, 93.5% of subjects were women, and the mean age at diagnosis was 53 (standard deviation [SD], 14.1 years). The mean total ESSDAI score was 6.1 (SD, 7.5).
Men had higher mean ESSDAI (8.1 vs. 6.0; P less than .001) and clinical ESSDAI (8.4 vs. 6.1; P less than .001) scores and were more likely to have a high disease activity state (22.5% vs. 11.7%; P less than .001). Domains that scored higher in men included lymphadenopathy (P less than .001), glandular (P less than .001), pulmonary (P = .001), peripheral nervous system (PNS) (P less than .001), and CNS (P less than .001).
The highest global ESSDAI scores were reported in patients younger than 35, but organ dominance differed by age group: The constitutional, lymphadenopathy, glandular, cutaneous, renal, hematologic, and biologic domains were highest in this age group, but pulmonary and peripheral nervous system were highest in patients over 65.
By ethnicity, the highest ESSDAI scores occurred in black/African-American patients (6.7), followed by white (6.5), Asian (5.4), and Hispanic (4.8; P less than .001). The organ-specific domains also tracked by ethnicity, with BAA patients experiencing the highest frequencies of activity in the lymphadenopathy, articular, neurologic, and biologic domains. White patients were more often affected in the glandular, cutaneous, and muscular domains, whereas Asians most often experienced the pulmonary, renal, and hematologic domains, and Hispanics the constitutional domain.
The survey included Europe, America, and Asia, and global ESSDAI scores were higher in the southern countries of Asia and Europe, and higher in countries below the equator in the Americas. The organ-by-organ activity scores had a differentiated pattern between northern and southern locales. Worldwide, the gradient of patients with moderate systemic activity (global ESSDAI score of 5 or higher) at diagnosis followed a north-south gradient.
The study had no specific funding, and the authors have no relevant financial disclosures. Dr. Mustelin, Dr. Scofield, and Dr. Chung have no relevant financial disclosures.
SOURCE: Brito-Zerón P et al. Rheumatology. 2019 Dec 24. doi: 10.1093/rheumatology/kez578.
The severity of Sjögren’s syndrome and its organ involvement has direct links to clinical characteristics that include age, gender, ethnicity, and geographical location, according to new research findings from a large, worldwide database of primary Sjögren’s syndrome patients.
Risk factors for more severe disease included male sex, earlier age at diagnosis, black/African-American (BAA) ethnicity, and living in more southerly countries, including below the equator. The authors hailed these factors as potentially helping to predict the presence of systemic disease in newly-diagnosed patients, as well as helping to determine the optimum follow-up strategy.
But not everyone agrees. In interviews, other experts suggested that the data were interesting and valuable, but were not ready to make reliable clinical predictions. “The predictive value of these data are limited when it comes to an individual patient sitting in front of you in the office,” said Tomas Mustelin, MD, professor of medicine at the University of Washington, Seattle.
“It would be an important clinical thing if you can figure out who’s at risk for systemic complications and who isn’t. This is a nice step in that direction,” said Hal Scofield, MD, professor of medicine and pathology at the University of Oklahoma, Oklahoma City, agreeing that the data were too preliminary to be broadly useful because there is too much overlap between different patient groups.
If there is one clinical message, it is that physicians should be looking beyond dry eyes and dry mouth in newly diagnosed Sjögren’s syndrome, according to Sarah Chung, MD, who is an acting instructor of rheumatology at the University of Washington. “It’s a reminder to investigate these extra-glandular manifestations, and a reminder that it is a heterogeneous presentation, so we have to keep an open mind and investigate thoroughly,” she said.
In the research published online in Rheumatology, first author Pilar Brito-Zerón, MD, PhD, of the University of Barcelona Hospital Clínic, and colleagues in the Sjögren Big Data Consortium used European League Against Rheumatism Sjögren’s syndrome disease activity index (ESSDAI) scores to examine phenotype and patient characteristics among 10,007 subjects drawn from the international consortium.
Overall, 93.5% of subjects were women, and the mean age at diagnosis was 53 (standard deviation [SD], 14.1 years). The mean total ESSDAI score was 6.1 (SD, 7.5).
Men had higher mean ESSDAI (8.1 vs. 6.0; P less than .001) and clinical ESSDAI (8.4 vs. 6.1; P less than .001) scores and were more likely to have a high disease activity state (22.5% vs. 11.7%; P less than .001). Domains that scored higher in men included lymphadenopathy (P less than .001), glandular (P less than .001), pulmonary (P = .001), peripheral nervous system (PNS) (P less than .001), and CNS (P less than .001).
The highest global ESSDAI scores were reported in patients younger than 35, but organ dominance differed by age group: The constitutional, lymphadenopathy, glandular, cutaneous, renal, hematologic, and biologic domains were highest in this age group, but pulmonary and peripheral nervous system were highest in patients over 65.
By ethnicity, the highest ESSDAI scores occurred in black/African-American patients (6.7), followed by white (6.5), Asian (5.4), and Hispanic (4.8; P less than .001). The organ-specific domains also tracked by ethnicity, with BAA patients experiencing the highest frequencies of activity in the lymphadenopathy, articular, neurologic, and biologic domains. White patients were more often affected in the glandular, cutaneous, and muscular domains, whereas Asians most often experienced the pulmonary, renal, and hematologic domains, and Hispanics the constitutional domain.
The survey included Europe, America, and Asia, and global ESSDAI scores were higher in the southern countries of Asia and Europe, and higher in countries below the equator in the Americas. The organ-by-organ activity scores had a differentiated pattern between northern and southern locales. Worldwide, the gradient of patients with moderate systemic activity (global ESSDAI score of 5 or higher) at diagnosis followed a north-south gradient.
The study had no specific funding, and the authors have no relevant financial disclosures. Dr. Mustelin, Dr. Scofield, and Dr. Chung have no relevant financial disclosures.
SOURCE: Brito-Zerón P et al. Rheumatology. 2019 Dec 24. doi: 10.1093/rheumatology/kez578.
The severity of Sjögren’s syndrome and its organ involvement has direct links to clinical characteristics that include age, gender, ethnicity, and geographical location, according to new research findings from a large, worldwide database of primary Sjögren’s syndrome patients.
Risk factors for more severe disease included male sex, earlier age at diagnosis, black/African-American (BAA) ethnicity, and living in more southerly countries, including below the equator. The authors hailed these factors as potentially helping to predict the presence of systemic disease in newly-diagnosed patients, as well as helping to determine the optimum follow-up strategy.
But not everyone agrees. In interviews, other experts suggested that the data were interesting and valuable, but were not ready to make reliable clinical predictions. “The predictive value of these data are limited when it comes to an individual patient sitting in front of you in the office,” said Tomas Mustelin, MD, professor of medicine at the University of Washington, Seattle.
“It would be an important clinical thing if you can figure out who’s at risk for systemic complications and who isn’t. This is a nice step in that direction,” said Hal Scofield, MD, professor of medicine and pathology at the University of Oklahoma, Oklahoma City, agreeing that the data were too preliminary to be broadly useful because there is too much overlap between different patient groups.
If there is one clinical message, it is that physicians should be looking beyond dry eyes and dry mouth in newly diagnosed Sjögren’s syndrome, according to Sarah Chung, MD, who is an acting instructor of rheumatology at the University of Washington. “It’s a reminder to investigate these extra-glandular manifestations, and a reminder that it is a heterogeneous presentation, so we have to keep an open mind and investigate thoroughly,” she said.
In the research published online in Rheumatology, first author Pilar Brito-Zerón, MD, PhD, of the University of Barcelona Hospital Clínic, and colleagues in the Sjögren Big Data Consortium used European League Against Rheumatism Sjögren’s syndrome disease activity index (ESSDAI) scores to examine phenotype and patient characteristics among 10,007 subjects drawn from the international consortium.
Overall, 93.5% of subjects were women, and the mean age at diagnosis was 53 (standard deviation [SD], 14.1 years). The mean total ESSDAI score was 6.1 (SD, 7.5).
Men had higher mean ESSDAI (8.1 vs. 6.0; P less than .001) and clinical ESSDAI (8.4 vs. 6.1; P less than .001) scores and were more likely to have a high disease activity state (22.5% vs. 11.7%; P less than .001). Domains that scored higher in men included lymphadenopathy (P less than .001), glandular (P less than .001), pulmonary (P = .001), peripheral nervous system (PNS) (P less than .001), and CNS (P less than .001).
The highest global ESSDAI scores were reported in patients younger than 35, but organ dominance differed by age group: The constitutional, lymphadenopathy, glandular, cutaneous, renal, hematologic, and biologic domains were highest in this age group, but pulmonary and peripheral nervous system were highest in patients over 65.
By ethnicity, the highest ESSDAI scores occurred in black/African-American patients (6.7), followed by white (6.5), Asian (5.4), and Hispanic (4.8; P less than .001). The organ-specific domains also tracked by ethnicity, with BAA patients experiencing the highest frequencies of activity in the lymphadenopathy, articular, neurologic, and biologic domains. White patients were more often affected in the glandular, cutaneous, and muscular domains, whereas Asians most often experienced the pulmonary, renal, and hematologic domains, and Hispanics the constitutional domain.
The survey included Europe, America, and Asia, and global ESSDAI scores were higher in the southern countries of Asia and Europe, and higher in countries below the equator in the Americas. The organ-by-organ activity scores had a differentiated pattern between northern and southern locales. Worldwide, the gradient of patients with moderate systemic activity (global ESSDAI score of 5 or higher) at diagnosis followed a north-south gradient.
The study had no specific funding, and the authors have no relevant financial disclosures. Dr. Mustelin, Dr. Scofield, and Dr. Chung have no relevant financial disclosures.
SOURCE: Brito-Zerón P et al. Rheumatology. 2019 Dec 24. doi: 10.1093/rheumatology/kez578.
FROM RHEUMATOLOGY
Half of SLE patients have incident neuropsychiatric events
Neuropsychiatric events occurred in just over half of all patients recently diagnosed with systemic lupus erythematosus and followed for an average of nearly 8 years in an international study of more than 1,800 patients.
Up to 30% of these neuropsychiatric (NP) events in up to 20% of the followed cohort were directly attributable to systemic lupus erythematosus (SLE) in a representative patient population, wrote John G. Hanly, MD, and associates in Annals of the Rheumatic Diseases. Their findings were consistent with prior reports, they added.
Another notable finding from follow-up of these 1,827 SLE patients was that among those without a history of SLE-related NP events at baseline, 74% remained free of NP events during the subsequent 10 years, wrote Dr. Hanly, professor of medicine and director of the lupus clinic at Dalhousie University, Halifax, N.S., and coauthors. Among patients free from SLE-associated NP events after 2 years, 84% remained event free during their remaining follow-up. SLE patients with a history of an NP event that subsequently resolved had a 72% rate of freedom from another NP event during 10 years of follow-up.
These findings came from patients recently diagnosed with SLE (within the preceding 15 months) and enrolled at any of 31 participating academic medical centers in North America, Europe, and Asia. The investigators considered preenrollment NP events to include those starting from 6 months prior to diagnosis of SLE until the time patients entered the study. They used case definitions for 19 SLE-associated NP events published by the American College of Rheumatology (Arthritis Rheum. 1999 Apr;42[4]:599-608). All enrolled patients underwent annual assessment for NP events, with follow-up continuing as long as 18 years.
The researchers identified NP events in 955 of the 1,827 enrolled patients, a 52% incidence, including 1,910 unique NP events that included episodes from each of the 19 NP event types, with 92% involving the central nervous system and 8% involving the peripheral nervous system. The percentage of NP events attributable to SLE ranged from 17% to 31%, and they occurred in 14%-21% of the studied patients, with the range reflecting various attribution models used in the analyses. Some patients remained in the same NP state, while others progressed through more than one state.
The study did not receive commercial funding. Dr. Hanly had no disclosures.
SOURCE: Hanly JG et al. Ann Rheum Dis. 2020 Jan 8. doi: 10.1136/annrheumdis-2019-216150.
Neuropsychiatric events occurred in just over half of all patients recently diagnosed with systemic lupus erythematosus and followed for an average of nearly 8 years in an international study of more than 1,800 patients.
Up to 30% of these neuropsychiatric (NP) events in up to 20% of the followed cohort were directly attributable to systemic lupus erythematosus (SLE) in a representative patient population, wrote John G. Hanly, MD, and associates in Annals of the Rheumatic Diseases. Their findings were consistent with prior reports, they added.
Another notable finding from follow-up of these 1,827 SLE patients was that among those without a history of SLE-related NP events at baseline, 74% remained free of NP events during the subsequent 10 years, wrote Dr. Hanly, professor of medicine and director of the lupus clinic at Dalhousie University, Halifax, N.S., and coauthors. Among patients free from SLE-associated NP events after 2 years, 84% remained event free during their remaining follow-up. SLE patients with a history of an NP event that subsequently resolved had a 72% rate of freedom from another NP event during 10 years of follow-up.
These findings came from patients recently diagnosed with SLE (within the preceding 15 months) and enrolled at any of 31 participating academic medical centers in North America, Europe, and Asia. The investigators considered preenrollment NP events to include those starting from 6 months prior to diagnosis of SLE until the time patients entered the study. They used case definitions for 19 SLE-associated NP events published by the American College of Rheumatology (Arthritis Rheum. 1999 Apr;42[4]:599-608). All enrolled patients underwent annual assessment for NP events, with follow-up continuing as long as 18 years.
The researchers identified NP events in 955 of the 1,827 enrolled patients, a 52% incidence, including 1,910 unique NP events that included episodes from each of the 19 NP event types, with 92% involving the central nervous system and 8% involving the peripheral nervous system. The percentage of NP events attributable to SLE ranged from 17% to 31%, and they occurred in 14%-21% of the studied patients, with the range reflecting various attribution models used in the analyses. Some patients remained in the same NP state, while others progressed through more than one state.
The study did not receive commercial funding. Dr. Hanly had no disclosures.
SOURCE: Hanly JG et al. Ann Rheum Dis. 2020 Jan 8. doi: 10.1136/annrheumdis-2019-216150.
Neuropsychiatric events occurred in just over half of all patients recently diagnosed with systemic lupus erythematosus and followed for an average of nearly 8 years in an international study of more than 1,800 patients.
Up to 30% of these neuropsychiatric (NP) events in up to 20% of the followed cohort were directly attributable to systemic lupus erythematosus (SLE) in a representative patient population, wrote John G. Hanly, MD, and associates in Annals of the Rheumatic Diseases. Their findings were consistent with prior reports, they added.
Another notable finding from follow-up of these 1,827 SLE patients was that among those without a history of SLE-related NP events at baseline, 74% remained free of NP events during the subsequent 10 years, wrote Dr. Hanly, professor of medicine and director of the lupus clinic at Dalhousie University, Halifax, N.S., and coauthors. Among patients free from SLE-associated NP events after 2 years, 84% remained event free during their remaining follow-up. SLE patients with a history of an NP event that subsequently resolved had a 72% rate of freedom from another NP event during 10 years of follow-up.
These findings came from patients recently diagnosed with SLE (within the preceding 15 months) and enrolled at any of 31 participating academic medical centers in North America, Europe, and Asia. The investigators considered preenrollment NP events to include those starting from 6 months prior to diagnosis of SLE until the time patients entered the study. They used case definitions for 19 SLE-associated NP events published by the American College of Rheumatology (Arthritis Rheum. 1999 Apr;42[4]:599-608). All enrolled patients underwent annual assessment for NP events, with follow-up continuing as long as 18 years.
The researchers identified NP events in 955 of the 1,827 enrolled patients, a 52% incidence, including 1,910 unique NP events that included episodes from each of the 19 NP event types, with 92% involving the central nervous system and 8% involving the peripheral nervous system. The percentage of NP events attributable to SLE ranged from 17% to 31%, and they occurred in 14%-21% of the studied patients, with the range reflecting various attribution models used in the analyses. Some patients remained in the same NP state, while others progressed through more than one state.
The study did not receive commercial funding. Dr. Hanly had no disclosures.
SOURCE: Hanly JG et al. Ann Rheum Dis. 2020 Jan 8. doi: 10.1136/annrheumdis-2019-216150.
FROM ANNALS OF THE RHEUMATIC DISEASES
Draft ACR Takayasu’s guidelines: Surgery is the last resort
ATLANTA – One of the goals in soon-to-be-published Takayasu’s arteritis guidelines from the American College of Rheumatology is to wean patients off high-dose steroids once they are in remission.
This recommendation is in opposition to another option – namely, switching these patients to low-dose glucocorticoids. The idea is to prevent long-term side effects, particularly in children. The guidelines also recommend against escalating immunotherapy for asymptomatic increases in inflammatory markers and generally recommend against surgery – stenting in most cases – unless there is threat to life, limb, or organ and also if limb pain is so severe it cramps quality of life and dose escalation doesn’t get the job done. If surgery is planned, patients should be on perioperative steroids if there’s active disease.
It’s draft guidance for now, but it’s probably what the final document will say when it’s published in 2020, according to a presentation at the annual meeting of the American College of Rheumatology by one of the authors, Anisha Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago. She gave a sneak preview at the meeting.
In general, severe, active Takayasu’s calls for high-dose oral steroids in conjunction with a nonsteroid immunosuppressive, such as methotrexate, azathioprine, leflunomide, or mycophenolate mofetil. There’s evidence that dual therapy gives a more durable remission and also reduces the need for steroids.
When that approach doesn’t do the trick, the next step is a tumor necrosis factor (TNF) inhibitor. There’s evidence for infliximab, adalimumab, certolizumab, and etanercept. Dr. Dua noted, “We still can consider” tocilizumab, but it failed to meet its primary endpoint in a randomized trial, and evidence for other biologics is sparse or nonexistent. “TNF inhibitors are the first line” for refractory disease, Dr. Dua said.
The steroid taper comes after 6-12 months of remission. Given their toxicity, “our goal for steroids is zero,” especially in pediatric populations. Even in remission, patients should have a clinical assessment, including inflammatory markers, every 3-12 months.
A rise in C-reactive protein or erythrocyte sedimentation rate, with no new symptoms, might be a reason for more frequent monitoring, but it’s not a reason to escalate immunosuppression. That should be kept in reserve for new vascular lesions, rapid progression on an old one, or worsening of organ or limb ischemia.
“We recommend [escalation] over surgical intervention” because patients often develop collateral circulation that solves the problem; it also gives the disease time to quiet down should the patient eventually go into surgery. Immediate surgery is reserved for organ or life-threatening disease, Dr. Dua said.
“Takayasu’s is different from other vasculitides in the sense that patients often present with certain nonspecific constitutional symptoms,” and there’s not a lot of pathology or histology to work with, “so we do tend to rely on imaging a lot,” Dr. Dua said.
Angiography has fallen out of favor because it’s invasive and exposes patients to radiation, among other problems. The field has moved to noninvasive imaging such as color Doppler ultrasound, CT angiography, magnetic resonance angiography, and PET CT.
“We do recommend regularly scheduled, noninvasive imaging every 6-12 months, in addition to the routine clinical assessment,” except in children with inactive disease; the risk of sedation outweighs the imaging benefit, Dr. Dua said.
In patients with single-vessel cranial or cervical stenosis, without symptoms, “we recommend medical over surgical management because of the risk of surgery. Surgery can be considered for multivessel involvement,” she said.
She and her colleagues also recommend medical management for renal artery stenosis, including antihypertensives and immunotherapy escalation for active disease. Surgery is considered for refractory hypertension or worsening kidney function
Dr. Dua is a primary investigator and adviser for Chemocentryx and an adviser for Novartis and AbbVie.
ATLANTA – One of the goals in soon-to-be-published Takayasu’s arteritis guidelines from the American College of Rheumatology is to wean patients off high-dose steroids once they are in remission.
This recommendation is in opposition to another option – namely, switching these patients to low-dose glucocorticoids. The idea is to prevent long-term side effects, particularly in children. The guidelines also recommend against escalating immunotherapy for asymptomatic increases in inflammatory markers and generally recommend against surgery – stenting in most cases – unless there is threat to life, limb, or organ and also if limb pain is so severe it cramps quality of life and dose escalation doesn’t get the job done. If surgery is planned, patients should be on perioperative steroids if there’s active disease.
It’s draft guidance for now, but it’s probably what the final document will say when it’s published in 2020, according to a presentation at the annual meeting of the American College of Rheumatology by one of the authors, Anisha Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago. She gave a sneak preview at the meeting.
In general, severe, active Takayasu’s calls for high-dose oral steroids in conjunction with a nonsteroid immunosuppressive, such as methotrexate, azathioprine, leflunomide, or mycophenolate mofetil. There’s evidence that dual therapy gives a more durable remission and also reduces the need for steroids.
When that approach doesn’t do the trick, the next step is a tumor necrosis factor (TNF) inhibitor. There’s evidence for infliximab, adalimumab, certolizumab, and etanercept. Dr. Dua noted, “We still can consider” tocilizumab, but it failed to meet its primary endpoint in a randomized trial, and evidence for other biologics is sparse or nonexistent. “TNF inhibitors are the first line” for refractory disease, Dr. Dua said.
The steroid taper comes after 6-12 months of remission. Given their toxicity, “our goal for steroids is zero,” especially in pediatric populations. Even in remission, patients should have a clinical assessment, including inflammatory markers, every 3-12 months.
A rise in C-reactive protein or erythrocyte sedimentation rate, with no new symptoms, might be a reason for more frequent monitoring, but it’s not a reason to escalate immunosuppression. That should be kept in reserve for new vascular lesions, rapid progression on an old one, or worsening of organ or limb ischemia.
“We recommend [escalation] over surgical intervention” because patients often develop collateral circulation that solves the problem; it also gives the disease time to quiet down should the patient eventually go into surgery. Immediate surgery is reserved for organ or life-threatening disease, Dr. Dua said.
“Takayasu’s is different from other vasculitides in the sense that patients often present with certain nonspecific constitutional symptoms,” and there’s not a lot of pathology or histology to work with, “so we do tend to rely on imaging a lot,” Dr. Dua said.
Angiography has fallen out of favor because it’s invasive and exposes patients to radiation, among other problems. The field has moved to noninvasive imaging such as color Doppler ultrasound, CT angiography, magnetic resonance angiography, and PET CT.
“We do recommend regularly scheduled, noninvasive imaging every 6-12 months, in addition to the routine clinical assessment,” except in children with inactive disease; the risk of sedation outweighs the imaging benefit, Dr. Dua said.
In patients with single-vessel cranial or cervical stenosis, without symptoms, “we recommend medical over surgical management because of the risk of surgery. Surgery can be considered for multivessel involvement,” she said.
She and her colleagues also recommend medical management for renal artery stenosis, including antihypertensives and immunotherapy escalation for active disease. Surgery is considered for refractory hypertension or worsening kidney function
Dr. Dua is a primary investigator and adviser for Chemocentryx and an adviser for Novartis and AbbVie.
ATLANTA – One of the goals in soon-to-be-published Takayasu’s arteritis guidelines from the American College of Rheumatology is to wean patients off high-dose steroids once they are in remission.
This recommendation is in opposition to another option – namely, switching these patients to low-dose glucocorticoids. The idea is to prevent long-term side effects, particularly in children. The guidelines also recommend against escalating immunotherapy for asymptomatic increases in inflammatory markers and generally recommend against surgery – stenting in most cases – unless there is threat to life, limb, or organ and also if limb pain is so severe it cramps quality of life and dose escalation doesn’t get the job done. If surgery is planned, patients should be on perioperative steroids if there’s active disease.
It’s draft guidance for now, but it’s probably what the final document will say when it’s published in 2020, according to a presentation at the annual meeting of the American College of Rheumatology by one of the authors, Anisha Dua, MD, an associate professor of rheumatology at Northwestern University, Chicago. She gave a sneak preview at the meeting.
In general, severe, active Takayasu’s calls for high-dose oral steroids in conjunction with a nonsteroid immunosuppressive, such as methotrexate, azathioprine, leflunomide, or mycophenolate mofetil. There’s evidence that dual therapy gives a more durable remission and also reduces the need for steroids.
When that approach doesn’t do the trick, the next step is a tumor necrosis factor (TNF) inhibitor. There’s evidence for infliximab, adalimumab, certolizumab, and etanercept. Dr. Dua noted, “We still can consider” tocilizumab, but it failed to meet its primary endpoint in a randomized trial, and evidence for other biologics is sparse or nonexistent. “TNF inhibitors are the first line” for refractory disease, Dr. Dua said.
The steroid taper comes after 6-12 months of remission. Given their toxicity, “our goal for steroids is zero,” especially in pediatric populations. Even in remission, patients should have a clinical assessment, including inflammatory markers, every 3-12 months.
A rise in C-reactive protein or erythrocyte sedimentation rate, with no new symptoms, might be a reason for more frequent monitoring, but it’s not a reason to escalate immunosuppression. That should be kept in reserve for new vascular lesions, rapid progression on an old one, or worsening of organ or limb ischemia.
“We recommend [escalation] over surgical intervention” because patients often develop collateral circulation that solves the problem; it also gives the disease time to quiet down should the patient eventually go into surgery. Immediate surgery is reserved for organ or life-threatening disease, Dr. Dua said.
“Takayasu’s is different from other vasculitides in the sense that patients often present with certain nonspecific constitutional symptoms,” and there’s not a lot of pathology or histology to work with, “so we do tend to rely on imaging a lot,” Dr. Dua said.
Angiography has fallen out of favor because it’s invasive and exposes patients to radiation, among other problems. The field has moved to noninvasive imaging such as color Doppler ultrasound, CT angiography, magnetic resonance angiography, and PET CT.
“We do recommend regularly scheduled, noninvasive imaging every 6-12 months, in addition to the routine clinical assessment,” except in children with inactive disease; the risk of sedation outweighs the imaging benefit, Dr. Dua said.
In patients with single-vessel cranial or cervical stenosis, without symptoms, “we recommend medical over surgical management because of the risk of surgery. Surgery can be considered for multivessel involvement,” she said.
She and her colleagues also recommend medical management for renal artery stenosis, including antihypertensives and immunotherapy escalation for active disease. Surgery is considered for refractory hypertension or worsening kidney function
Dr. Dua is a primary investigator and adviser for Chemocentryx and an adviser for Novartis and AbbVie.
REPORTING FROM ACR 2019
Methotrexate gives durable remission from idiopathic granulomatous mastitis
ATLANTA – Methotrexate, in combination with prednisone, might be emerging as the go-to option for idiopathic granulomatous mastitis, according to investigators from Oregon Health & Science University, Portland.
Idiopathic granulomatous mastitis (IGM) is an inflammatory disease in which granulomas form in breast tissue. It strikes mostly young to middle-aged women with painful, firm breast masses, sometimes with redness and drainage. Diagnosis is by biopsy with rule-out of known causes.
IGM does not respond to antibiotics. Prednisone and surgery have been the traditional approaches, but masses can recur after surgery, and a year or more of prednisone, with the weight gain and side effects, is problematic. As a result, cases are increasingly being referred to rheumatologists for other options, said lead investigator Sarah Ringsted, MD, a rheumatology fellow at the university.
A study she presented at the annual meeting of the American College of Rheumatology and previous work from others builds a case for methotrexate, which often seems to put the disease in remission and allows for shorter glucocorticoid courses. These days, “I offer this to patients as a great option. It’s really nice to have, instead of having women go on months and months of high-dose steroids, and I think we can save patients from unnecessary” surgery, Dr. Ringsted said.
Her usual regimen these days is methotrexate 15-20 mg/week for 12-18 months, with high-dose prednisone (greater than 20 mg/day) for the first 3 months, followed by a taper.
Dr. Ringsted and associates compared 23 women treated at the university during 2007-2018. Just 5 of the 12 women (42%) treated with high-dose prednisone alone went into remission and did not relapse over a mean follow-up of 27 months. Two out of three women who had both high-dose glucocorticoids and surgery achieved remission without relapse, as did all three women who received methotrexate and high-dose glucocorticoids (one also had surgery). Five other patients were treated with other options; just two had a durable remission.
The numbers are small, but they add to two previous reports. Among 19 women who had failed other treatments, 94% improved and 75% went into remission with 15 months of methotrexate in a review from Stanford (Calif.) University. An Iranian study of 17 patients treated with methotrexate, and also glucocorticoids in some, had a relapse rate of only 17.8%.
There were several cases of both inflammatory arthritis and erythema nodosum in the Oregon series, a higher incidence than what has been reported before for IGM. “It’s interesting because it makes me think of sarcoidosis. There have been cases of sarcoidosis causing mastitis, but mostly in patients with other features” of the disease. “It makes me wonder if any of these women will develop sarcoidosis later on; I think that’s an interesting question,” Dr. Ringsted said.
Women in the study were an average age of 32 years, and over half were Hispanic, which is associated with a higher risk for IGM. Almost all the women had been pregnant before and had breast fed in the previous 5 years. Cancer, tuberculosis, and fungal infections were among the things ruled out before mastitis was deemed idiopathic.
Women with IGM tend to be of childbearing age, and must be cautioned against the teratogenic effects of methotrexate, Dr. Ringsted noted.
There was no external funding, and the investigators didn’t report any disclosures.
SOURCE: Ringsted S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 386.
ATLANTA – Methotrexate, in combination with prednisone, might be emerging as the go-to option for idiopathic granulomatous mastitis, according to investigators from Oregon Health & Science University, Portland.
Idiopathic granulomatous mastitis (IGM) is an inflammatory disease in which granulomas form in breast tissue. It strikes mostly young to middle-aged women with painful, firm breast masses, sometimes with redness and drainage. Diagnosis is by biopsy with rule-out of known causes.
IGM does not respond to antibiotics. Prednisone and surgery have been the traditional approaches, but masses can recur after surgery, and a year or more of prednisone, with the weight gain and side effects, is problematic. As a result, cases are increasingly being referred to rheumatologists for other options, said lead investigator Sarah Ringsted, MD, a rheumatology fellow at the university.
A study she presented at the annual meeting of the American College of Rheumatology and previous work from others builds a case for methotrexate, which often seems to put the disease in remission and allows for shorter glucocorticoid courses. These days, “I offer this to patients as a great option. It’s really nice to have, instead of having women go on months and months of high-dose steroids, and I think we can save patients from unnecessary” surgery, Dr. Ringsted said.
Her usual regimen these days is methotrexate 15-20 mg/week for 12-18 months, with high-dose prednisone (greater than 20 mg/day) for the first 3 months, followed by a taper.
Dr. Ringsted and associates compared 23 women treated at the university during 2007-2018. Just 5 of the 12 women (42%) treated with high-dose prednisone alone went into remission and did not relapse over a mean follow-up of 27 months. Two out of three women who had both high-dose glucocorticoids and surgery achieved remission without relapse, as did all three women who received methotrexate and high-dose glucocorticoids (one also had surgery). Five other patients were treated with other options; just two had a durable remission.
The numbers are small, but they add to two previous reports. Among 19 women who had failed other treatments, 94% improved and 75% went into remission with 15 months of methotrexate in a review from Stanford (Calif.) University. An Iranian study of 17 patients treated with methotrexate, and also glucocorticoids in some, had a relapse rate of only 17.8%.
There were several cases of both inflammatory arthritis and erythema nodosum in the Oregon series, a higher incidence than what has been reported before for IGM. “It’s interesting because it makes me think of sarcoidosis. There have been cases of sarcoidosis causing mastitis, but mostly in patients with other features” of the disease. “It makes me wonder if any of these women will develop sarcoidosis later on; I think that’s an interesting question,” Dr. Ringsted said.
Women in the study were an average age of 32 years, and over half were Hispanic, which is associated with a higher risk for IGM. Almost all the women had been pregnant before and had breast fed in the previous 5 years. Cancer, tuberculosis, and fungal infections were among the things ruled out before mastitis was deemed idiopathic.
Women with IGM tend to be of childbearing age, and must be cautioned against the teratogenic effects of methotrexate, Dr. Ringsted noted.
There was no external funding, and the investigators didn’t report any disclosures.
SOURCE: Ringsted S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 386.
ATLANTA – Methotrexate, in combination with prednisone, might be emerging as the go-to option for idiopathic granulomatous mastitis, according to investigators from Oregon Health & Science University, Portland.
Idiopathic granulomatous mastitis (IGM) is an inflammatory disease in which granulomas form in breast tissue. It strikes mostly young to middle-aged women with painful, firm breast masses, sometimes with redness and drainage. Diagnosis is by biopsy with rule-out of known causes.
IGM does not respond to antibiotics. Prednisone and surgery have been the traditional approaches, but masses can recur after surgery, and a year or more of prednisone, with the weight gain and side effects, is problematic. As a result, cases are increasingly being referred to rheumatologists for other options, said lead investigator Sarah Ringsted, MD, a rheumatology fellow at the university.
A study she presented at the annual meeting of the American College of Rheumatology and previous work from others builds a case for methotrexate, which often seems to put the disease in remission and allows for shorter glucocorticoid courses. These days, “I offer this to patients as a great option. It’s really nice to have, instead of having women go on months and months of high-dose steroids, and I think we can save patients from unnecessary” surgery, Dr. Ringsted said.
Her usual regimen these days is methotrexate 15-20 mg/week for 12-18 months, with high-dose prednisone (greater than 20 mg/day) for the first 3 months, followed by a taper.
Dr. Ringsted and associates compared 23 women treated at the university during 2007-2018. Just 5 of the 12 women (42%) treated with high-dose prednisone alone went into remission and did not relapse over a mean follow-up of 27 months. Two out of three women who had both high-dose glucocorticoids and surgery achieved remission without relapse, as did all three women who received methotrexate and high-dose glucocorticoids (one also had surgery). Five other patients were treated with other options; just two had a durable remission.
The numbers are small, but they add to two previous reports. Among 19 women who had failed other treatments, 94% improved and 75% went into remission with 15 months of methotrexate in a review from Stanford (Calif.) University. An Iranian study of 17 patients treated with methotrexate, and also glucocorticoids in some, had a relapse rate of only 17.8%.
There were several cases of both inflammatory arthritis and erythema nodosum in the Oregon series, a higher incidence than what has been reported before for IGM. “It’s interesting because it makes me think of sarcoidosis. There have been cases of sarcoidosis causing mastitis, but mostly in patients with other features” of the disease. “It makes me wonder if any of these women will develop sarcoidosis later on; I think that’s an interesting question,” Dr. Ringsted said.
Women in the study were an average age of 32 years, and over half were Hispanic, which is associated with a higher risk for IGM. Almost all the women had been pregnant before and had breast fed in the previous 5 years. Cancer, tuberculosis, and fungal infections were among the things ruled out before mastitis was deemed idiopathic.
Women with IGM tend to be of childbearing age, and must be cautioned against the teratogenic effects of methotrexate, Dr. Ringsted noted.
There was no external funding, and the investigators didn’t report any disclosures.
SOURCE: Ringsted S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 386.
REPORTING FROM ACR 2019