American College of Rheumatology (ACR): State-of-the-Art Clinical Symposium

CHICAGO – The risk of active disease in pregnant women with systemic lupus erythematosus far outweighs the risks of most medications.

Indeed, the risk of pregnancy loss doubles if lupus is active during pregnancy and jumps fourfold if the autoimmune disease is active in the 3 months before conception.

"My general rule is that the inflammation of active lupus is more dangerous to a pregnancy than medications," said Dr. Megan Clowse, director of the Duke University Autoimmunity in Pregnancy Registry in Durham, N.C. "We don’t have a medication that will cause a 40% pregnancy loss. So I think it’s important to continue medications within this population, although some drugs are certainly better than others."

Patrice Wendling/IMNG Medical Media

She advocates the use of hydroxychloroquine (Plaquenil) as the best way to prevent a systemic lupus erythematosus (SLE) flare. It’s a pregnancy category C drug because of reports of hearing abnormalities in children exposed to high doses of chloroquine (Aralen), but there are no clear fetal risks with hydroxychloroquine itself, particularly at the doses used by rheumatologists, she said. Moreover, several reports have suggested that hydroxychloroquine discontinuation during pregnancy may precipitate SLE flares, thereby worsening pregnancy prognosis.

The one exception to hydroxychloroquine use in SLE is the patient who’s been off the drug for years and is no longer symptomatic but becomes pregnant. "I don’t force those women back on their hydroxychloroquine, but basically everybody else should be on it," Dr. Clowse said at a symposium sponsored by the American College of Rheumatology.

For women with more active SLE, consider the use of azathioprine (Azasan, Imuran). It is a pregnancy category D drug due to the risk for fetal immunosuppression at delivery, but its use in SLE pregnancy is supported by extensive data among renal transplant patients, who have a higher rate of prematurity than SLE patients.

Azathioprine is most effective in preventing SLE flare in pregnancy, but Dr. Clowse said she has not been as impressed with its ability to treat flares during pregnancy. In her own recent study, azathioprine did not prevent pregnancy loss, and was actually associated with higher rates of loss among women with high-activity SLE.

When SLE flares occur, they need to be treated promptly, she stressed. Prednisone is probably the most effective treatment, although intravenous immunoglobulin may be a reasonable option. Prednisone is metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. In contrast, the fluorinated corticosteroid betamethasone (Betnesol injection) is not metabolized and is transferred to the fetus, so it should not be used during pregnancy. Prednisone may decrease birth weight and is associated with a modest, threefold increased risk for cleft lip and palate, but this is really a first-trimester risk, she noted.

Drugs to avoid in pregnancy include cyclophosphamide (Cytoxan), mycophenolate mofetil (CellCept), and belimumab (Benlysta). A review of 26 pregnancies in 18 renal transplant patients receiving mycophenolate reported that 11 ended in spontaneous abortions and 10 in preterm births, and there were 4 cases of congenital anomalies (Transplantation 2006;82:1698-702). Not only was the 26% birth defect rate staggering compared with the 3% seen in the general population, but three of the infants had microtia. This was not simply underdeveloped pinnae, but the ears were located in the wrong place on the head, resulting in the babies being deaf, Dr. Clowse warned.

Although teratogenicity has not been observed in animals on belimumab, GlaxoSmithKline recently launched a global Benlysta Pregnancy Registry to prospectively collect data on birth defects and other pregnancy outcomes from women receiving belimumab within the 4 months prior to and/or during pregnancy (telephone: 1-877-681-6296).

Dr. Clowse said she recently began putting most of her pregnant SLE patients on aspirin 81 mg/day to prevent preeclampsia. Data from high-risk, nonlupus patients suggest aspirin may decrease the risk of preterm birth, preeclampsia, maternal hypertension, and low-birth weight without increasing the risk of congenital anomalies or ductus arteriosus closure observed with regular aspirin.

"It also, to be honest, takes away that whole discussion of low anticardiolipin antibodies and what do you do," she added.

Pregnant women with SLE should be closely monitored by a rheumatologist and an obstetrician skilled in high-risk pregnancies. Key parameters to monitor are hypertension, particularly in the first trimester, as this can increase the risk of pregnancy loss, preterm birth, and preeclampsia by up to 40%; and proteinuria, which may rise modestly during pregnancy due to increased renal function. More than a doubling or a 1-g increase of proteinuria, however, should raise the alarm, Dr. Clowse said.

To achieve the best possible pregnancy outcome, women with SLE should be advised to avoid pregnancy when SLE is active. Dr. Clowse said it’s recently come to her attention that in North Carolina and other parts of the United States where abstinence-only education has been the law of the land for the past dozen years, this may mean having that first conversation about contraception with a patient already in her 20s.

"I think it’s really important that we address this with our rheumatology patients," she said.

Dr. Clowse said progesterone-only contraceptives are probably the safest method in SLE patients, with medroxyprogesterone injection (Depo-Provera) generally well tolerated, and the 3-year etonogestrel implant (Implanon) is better tolerated than the levonorgestrel implant (Norplant). She also advises her SLE patients to use barrier methods and to pick up levonorgestrel (Plan B One-Step) on the way home from the clinic to have on hand for emergencies.

Dr. Clowse reported consulting for UCB and receiving grant support from the Arthritis Foundation.

CHICAGO – The risk of active disease in pregnant women with systemic lupus erythematosus far outweighs the risks of most medications.

Indeed, the risk of pregnancy loss doubles if lupus is active during pregnancy and jumps fourfold if the autoimmune disease is active in the 3 months before conception.

"My general rule is that the inflammation of active lupus is more dangerous to a pregnancy than medications," said Dr. Megan Clowse, director of the Duke University Autoimmunity in Pregnancy Registry in Durham, N.C. "We don’t have a medication that will cause a 40% pregnancy loss. So I think it’s important to continue medications within this population, although some drugs are certainly better than others."

Patrice Wendling/IMNG Medical Media

She advocates the use of hydroxychloroquine (Plaquenil) as the best way to prevent a systemic lupus erythematosus (SLE) flare. It’s a pregnancy category C drug because of reports of hearing abnormalities in children exposed to high doses of chloroquine (Aralen), but there are no clear fetal risks with hydroxychloroquine itself, particularly at the doses used by rheumatologists, she said. Moreover, several reports have suggested that hydroxychloroquine discontinuation during pregnancy may precipitate SLE flares, thereby worsening pregnancy prognosis.

The one exception to hydroxychloroquine use in SLE is the patient who’s been off the drug for years and is no longer symptomatic but becomes pregnant. "I don’t force those women back on their hydroxychloroquine, but basically everybody else should be on it," Dr. Clowse said at a symposium sponsored by the American College of Rheumatology.

For women with more active SLE, consider the use of azathioprine (Azasan, Imuran). It is a pregnancy category D drug due to the risk for fetal immunosuppression at delivery, but its use in SLE pregnancy is supported by extensive data among renal transplant patients, who have a higher rate of prematurity than SLE patients.

Azathioprine is most effective in preventing SLE flare in pregnancy, but Dr. Clowse said she has not been as impressed with its ability to treat flares during pregnancy. In her own recent study, azathioprine did not prevent pregnancy loss, and was actually associated with higher rates of loss among women with high-activity SLE.

When SLE flares occur, they need to be treated promptly, she stressed. Prednisone is probably the most effective treatment, although intravenous immunoglobulin may be a reasonable option. Prednisone is metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. In contrast, the fluorinated corticosteroid betamethasone (Betnesol injection) is not metabolized and is transferred to the fetus, so it should not be used during pregnancy. Prednisone may decrease birth weight and is associated with a modest, threefold increased risk for cleft lip and palate, but this is really a first-trimester risk, she noted.

Drugs to avoid in pregnancy include cyclophosphamide (Cytoxan), mycophenolate mofetil (CellCept), and belimumab (Benlysta). A review of 26 pregnancies in 18 renal transplant patients receiving mycophenolate reported that 11 ended in spontaneous abortions and 10 in preterm births, and there were 4 cases of congenital anomalies (Transplantation 2006;82:1698-702). Not only was the 26% birth defect rate staggering compared with the 3% seen in the general population, but three of the infants had microtia. This was not simply underdeveloped pinnae, but the ears were located in the wrong place on the head, resulting in the babies being deaf, Dr. Clowse warned.

Although teratogenicity has not been observed in animals on belimumab, GlaxoSmithKline recently launched a global Benlysta Pregnancy Registry to prospectively collect data on birth defects and other pregnancy outcomes from women receiving belimumab within the 4 months prior to and/or during pregnancy (telephone: 1-877-681-6296).

Dr. Clowse said she recently began putting most of her pregnant SLE patients on aspirin 81 mg/day to prevent preeclampsia. Data from high-risk, nonlupus patients suggest aspirin may decrease the risk of preterm birth, preeclampsia, maternal hypertension, and low-birth weight without increasing the risk of congenital anomalies or ductus arteriosus closure observed with regular aspirin.

"It also, to be honest, takes away that whole discussion of low anticardiolipin antibodies and what do you do," she added.

Pregnant women with SLE should be closely monitored by a rheumatologist and an obstetrician skilled in high-risk pregnancies. Key parameters to monitor are hypertension, particularly in the first trimester, as this can increase the risk of pregnancy loss, preterm birth, and preeclampsia by up to 40%; and proteinuria, which may rise modestly during pregnancy due to increased renal function. More than a doubling or a 1-g increase of proteinuria, however, should raise the alarm, Dr. Clowse said.

To achieve the best possible pregnancy outcome, women with SLE should be advised to avoid pregnancy when SLE is active. Dr. Clowse said it’s recently come to her attention that in North Carolina and other parts of the United States where abstinence-only education has been the law of the land for the past dozen years, this may mean having that first conversation about contraception with a patient already in her 20s.

"I think it’s really important that we address this with our rheumatology patients," she said.

Dr. Clowse said progesterone-only contraceptives are probably the safest method in SLE patients, with medroxyprogesterone injection (Depo-Provera) generally well tolerated, and the 3-year etonogestrel implant (Implanon) is better tolerated than the levonorgestrel implant (Norplant). She also advises her SLE patients to use barrier methods and to pick up levonorgestrel (Plan B One-Step) on the way home from the clinic to have on hand for emergencies.

Dr. Clowse reported consulting for UCB and receiving grant support from the Arthritis Foundation.

CHICAGO – The risk of active disease in pregnant women with systemic lupus erythematosus far outweighs the risks of most medications.

Indeed, the risk of pregnancy loss doubles if lupus is active during pregnancy and jumps fourfold if the autoimmune disease is active in the 3 months before conception.

"My general rule is that the inflammation of active lupus is more dangerous to a pregnancy than medications," said Dr. Megan Clowse, director of the Duke University Autoimmunity in Pregnancy Registry in Durham, N.C. "We don’t have a medication that will cause a 40% pregnancy loss. So I think it’s important to continue medications within this population, although some drugs are certainly better than others."

Patrice Wendling/IMNG Medical Media

She advocates the use of hydroxychloroquine (Plaquenil) as the best way to prevent a systemic lupus erythematosus (SLE) flare. It’s a pregnancy category C drug because of reports of hearing abnormalities in children exposed to high doses of chloroquine (Aralen), but there are no clear fetal risks with hydroxychloroquine itself, particularly at the doses used by rheumatologists, she said. Moreover, several reports have suggested that hydroxychloroquine discontinuation during pregnancy may precipitate SLE flares, thereby worsening pregnancy prognosis.

The one exception to hydroxychloroquine use in SLE is the patient who’s been off the drug for years and is no longer symptomatic but becomes pregnant. "I don’t force those women back on their hydroxychloroquine, but basically everybody else should be on it," Dr. Clowse said at a symposium sponsored by the American College of Rheumatology.

For women with more active SLE, consider the use of azathioprine (Azasan, Imuran). It is a pregnancy category D drug due to the risk for fetal immunosuppression at delivery, but its use in SLE pregnancy is supported by extensive data among renal transplant patients, who have a higher rate of prematurity than SLE patients.

Azathioprine is most effective in preventing SLE flare in pregnancy, but Dr. Clowse said she has not been as impressed with its ability to treat flares during pregnancy. In her own recent study, azathioprine did not prevent pregnancy loss, and was actually associated with higher rates of loss among women with high-activity SLE.

When SLE flares occur, they need to be treated promptly, she stressed. Prednisone is probably the most effective treatment, although intravenous immunoglobulin may be a reasonable option. Prednisone is metabolized by the placenta, allowing only 10% of the maternal dose to reach the fetus. In contrast, the fluorinated corticosteroid betamethasone (Betnesol injection) is not metabolized and is transferred to the fetus, so it should not be used during pregnancy. Prednisone may decrease birth weight and is associated with a modest, threefold increased risk for cleft lip and palate, but this is really a first-trimester risk, she noted.

Drugs to avoid in pregnancy include cyclophosphamide (Cytoxan), mycophenolate mofetil (CellCept), and belimumab (Benlysta). A review of 26 pregnancies in 18 renal transplant patients receiving mycophenolate reported that 11 ended in spontaneous abortions and 10 in preterm births, and there were 4 cases of congenital anomalies (Transplantation 2006;82:1698-702). Not only was the 26% birth defect rate staggering compared with the 3% seen in the general population, but three of the infants had microtia. This was not simply underdeveloped pinnae, but the ears were located in the wrong place on the head, resulting in the babies being deaf, Dr. Clowse warned.

Although teratogenicity has not been observed in animals on belimumab, GlaxoSmithKline recently launched a global Benlysta Pregnancy Registry to prospectively collect data on birth defects and other pregnancy outcomes from women receiving belimumab within the 4 months prior to and/or during pregnancy (telephone: 1-877-681-6296).

Dr. Clowse said she recently began putting most of her pregnant SLE patients on aspirin 81 mg/day to prevent preeclampsia. Data from high-risk, nonlupus patients suggest aspirin may decrease the risk of preterm birth, preeclampsia, maternal hypertension, and low-birth weight without increasing the risk of congenital anomalies or ductus arteriosus closure observed with regular aspirin.

"It also, to be honest, takes away that whole discussion of low anticardiolipin antibodies and what do you do," she added.

Pregnant women with SLE should be closely monitored by a rheumatologist and an obstetrician skilled in high-risk pregnancies. Key parameters to monitor are hypertension, particularly in the first trimester, as this can increase the risk of pregnancy loss, preterm birth, and preeclampsia by up to 40%; and proteinuria, which may rise modestly during pregnancy due to increased renal function. More than a doubling or a 1-g increase of proteinuria, however, should raise the alarm, Dr. Clowse said.

To achieve the best possible pregnancy outcome, women with SLE should be advised to avoid pregnancy when SLE is active. Dr. Clowse said it’s recently come to her attention that in North Carolina and other parts of the United States where abstinence-only education has been the law of the land for the past dozen years, this may mean having that first conversation about contraception with a patient already in her 20s.

"I think it’s really important that we address this with our rheumatology patients," she said.

Dr. Clowse said progesterone-only contraceptives are probably the safest method in SLE patients, with medroxyprogesterone injection (Depo-Provera) generally well tolerated, and the 3-year etonogestrel implant (Implanon) is better tolerated than the levonorgestrel implant (Norplant). She also advises her SLE patients to use barrier methods and to pick up levonorgestrel (Plan B One-Step) on the way home from the clinic to have on hand for emergencies.

Dr. Clowse reported consulting for UCB and receiving grant support from the Arthritis Foundation.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Although clinical trials in rheumatoid arthritis have shown that treating to a target improves outcomes, uptake of the strategy in clinical practice continues to lag.

One of the greatest challenges is that although the treat-to-target recommendations say clinicians should change treatment based on objective outcome measures, no one has proved that doing so makes a difference in daily practice. Instead, the data on the strategy comes from prospective clinical trials, Dr. Sergio Schwartzman said at a symposium sponsored by the American College of Rheumatology (ACR).

Patrice Wendling/IMNG Medical Media

The treat-to-target strategy requires that clinicians choose a disease activity measure and measure consistently. But there are a myriad of outcome measures that clinicians can measure and a lack of consensus on which instrument to use. The American College of Rheumatology just published six recommended outcome measures for use in clinical practice based on systematic literature review (Arthritis Care Res. 2012;64:640-7). They are: the Clinical Disease Activity Index (CDAI); Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein) (DAS28); Patient Activity Scale (PAS); PAS-II; Routine Assessment of Patient Index Data with three measures (RAPID-3); and the Simplified Disease Activity Index (SDAI).

Dr. Schwartzman, an associate attending rheumatologist from the Hospital for Special Surgery in New York City said the he uses the CDAI in his practice because it’s fast and immediate. Also, both the CDAI and SDAI are highly correlated with the DAS28 and ACR 20/50/70 response – two composite measures frequently used as outcomes in rheumatoid arthritis (RA) clinical trials.

"To do a 28-joint count takes about 90 seconds, and this has been published," he noted.

One limitation of composite measurement tools is that a tender joint count may be abnormal during a joint assessment but not necessarily reflective of active RA. The perfect example of this is the patient with inflammatory osteoarthritis and those with RA and fibromyalgia, Dr. Schwartzman said. Differentiating bony or fibrous swelling from joints truly swollen from synovitis can also be tricky. Composite measurement tools also frequently include comorbid symptoms such as back pain that have nothing to do with arthritis and have a floor effect once the patient has a disability, he added.

Ultrasound is increasingly being used in practice, with some evidence to suggest that the new German US 7 (G7) score is a viable option for following patients over time. The G7 uses a 3-point scale to score synovitis, peritendinitis /tenosynovitis, and erosions in seven joints in the clinically dominant hand and foot. A pilot study involving 120 RA patients in a daily rheumatology practice found that the G7 score significantly reflected response to disease-modifying antirheumatic drug and/or tumor necrosis factor (TNF)-alpha therapy at 6 months when compared with the DAS28 (Arthritis Rheum. 2009;61:1194-201).

The main drawback is that the G7 is relatively time consuming to perform at about 20-30 minutes in the hands of an experienced ultrasonographer, Dr. Schwartzman said. As with any outcome measure, there is also the time needed to review and document the outcome measures.

Inroads are being made with the use of biomarkers, but he argued that this approach is still in development. Crescendo Bioscience’s multi-protein Vectra DA biomarker blood test is approved in the United States to monitor disease activity, but reimbursement is by no means universal.

Dr. Schwartzman said that while many rheumatologists are measuring disease activity, they often fail to identify a therapeutic target and to utilize the measurement in a defined time frame.

"The weakness in the concept of treat-to-target is that many of us do the first, but don’t necessarily do the second and third pieces," he said.

Session moderator Dr. John Cush, medical director of Baylor Research Institute in Dallas, said: "I don’t think there is any evidence that anyone actually uses treat-to-target in practice other than a few crazies like myself."

He said most clinicians remain adverse to the treat-to-target strategy despite strong evidence from trials such as TICORA (Tight Control for Rheumatoid Arthritis) that it works (Lancet 2004;364:263-69), and asked Dr. Schwartman, "What is it going to take for people to do it, besides third-party payers mandating it?"

Dr. Schwartzman responded that third-party payers will indeed ultimately mandate outcome measures, and asked Dr. Cush whether he personalizes therapy or uses a protocol once an outcome is reached. Dr. Cush said he is "answerable to the numbers," but personalizes therapy for his patients. Just because he recommends a change in therapy, however, doesn’t mean patients will accept it, he added.

Dr. Schwartzman disclosed having financial relationships with Amgen, Abbott, Genentech, Janssen, Pfizer, Roche, and UCB. Dr. Cush reported financial relationships with Abbott, Celgene, Centocor, Genentech, Pfizer, Roche, UCB, and Wyeth/Amgen.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – Rheumatic conditions associated with HIV infection have declined since the introduction of highly active antiretroviral therapy, but they remain common in patients with HIV infection.

Rheumatic conditions have been described in HIV infection since the 1980s, with a recent review suggesting an overall prevalence today of about 9% (Curr. Opin. Rheumatol. 2009;21:404-10).

In the era before widespread use of highly active antiretroviral therapy (HAART), the presentation of many individuals with HIV involved arthralgias, psoriatic arthritis, reactive arthritis, and diffuse infiltrative lymphocytosis syndrome (DILS). The prevalence of these syndromes decreased dramatically after the introduction of HAART in 1997. Findings from a recent chart review showed that 34% of 306 new HIV referrals to a Houston rheumatology clinic between 1994 and 1997 had DILS, compared with only 7.5% of 346 new referrals between 1998 and 2003 (odds ratio, 4.8; P less than .000001) (Arthritis Rheum. 2006;55:466-72).

In the HAART era, however, there has been an increase in osteoporosis and osteonecrosis in patients with HIV infection, which is actually thought to be secondary to some of the medications they take, said Dr. Michael P. Angarone, a clinical instructor in medicine–infectious diseases at Northwestern University in Chicago.

"Antiretroviral therapy has had a substantial impact on the development of rheumatologic conditions," he said at a symposium sponsored by the American College of Rheumatology.

The use of immunomodulating therapy can be challenging in patients with compromised immunity due to chronic HIV infection. Immunomodulatory therapy may decrease further their already lowered CD4 T-cell count, thereby increasing their risk for infection and the consequences of immunodeficiency. In addition, the therapy may actually promote viral replication.

There is a paucity of data in the rheumatology setting, but successful immunomodulatory therapy has been reported among HIV-infected patients in the transplant literature. CD4 counts and HIV viral loads remained stable, and there was no evidence of worsening HIV in 150 patients on a stable antiretroviral regimen who underwent kidney transplantation and received antithymocyte antibodies, calcineurin inhibitors, or high-dose corticosteroids (N. Engl. J. Med. 2010;363:2004-14). The one caveat to the prospective data is that those receiving antithymocyte antibodies initially experienced a decrease in CD4 T cells, but over time antibody levels slowly increased, said Dr. Angarone, who pointed out that this pattern is also seen in HIV-negative individuals who undergo antithymocyte antibody therapy.

"So the lesson we’ve learned from the transplant population is that we can indeed immunosuppress our HIV-infected individuals," he added.

Although anti–tumor necrosis factor (anti-TNF) therapies are being used to treat rheumatologic conditions, there have been no prospective trials of anti-TNF agents in HIV-infected patients and little in the way of adverse event reporting in patients with chronic viral infections. Initial thinking was that HIV utilizes TNF to replicate, and subsequently causes a decrease in CD-4 T cells, Dr. Angarone explained. A study involving an early TNF-alpha inhibitor, however, demonstrated no changes in CD4 cell counts or plasma HIV RNA levels, as feared, among six HIV-infected patients (J. Infect. Dis. 1996;174:63-8).

In addition, a recent case series reported excellent clinical responses in five of eight HIV-positive patients who received etanercept, infliximab, or adalimumab for a variety of rheumatologic diseases, including rheumatoid, psoriatic, and reactive arthritis; ankylosing spondylitis; and undifferentiated spondyloarthritis that was refractory to standard therapy (Ann. Rheum. Dis. 2008;67:710-2). CD4 counts reached a low of 240-923 cells/mm³ during treatment versus 268-974 cells/mm³ at baseline, while HIV viral loads remained undetectable in 50% versus 63% at baseline. No significant clinical adverse effects were reported. One patient had a substantial increase in HIV viral load, but this patient was not on antivirals, and the viral load decreased with anti-TNF discontinuation, Dr. Angarone pointed out.

"Immunomodulatory therapy appears to be safe in individuals with HIV infection. However, I think careful selection of patients needs to be undertaken, and you have to monitor these patients very closely," he said. "Ideally, you want an individual with a CD4 count greater than 200 [cells/mm³] and an HIV viral load that is undetectable [greater than 50 copies/mL] and you want that individual on antiretroviral therapy."

Given the variety of rheumatologic presentations of HIV, Dr. Angarone suggested that screening for HIV infection should be considered for all patients. Routine testing for HIV has been shown to be as cost effective as breast and colon cancer screening, and is recommended by the Centers for Disease Control and Prevention as part of routine screening in all health care settings for those ages 13 to 64, regardless of risk, he noted.

Dr. Angarone reported no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.