When Robin Orr was admitted to the ED of Santa Barbara Cottage Hospital (Calif.), she brought a long history of experience with hospitals, both as a patient and in her professional life. Orr is a cancer survivor who had undergone back surgery several months earlier and had suffered from increasing back pain since the surgery. Late one Friday night in June 24, 2005, the pain was so intense that Orr’s care partner, Sue Cook, brought her to the ED. Orr was given morphine and taken to a room for the remainder of the night.

Who Is Robin Orr?

Orr was no ordinary hospital patient. With nearly three decades of experience as a healthcare professional working with hospitals, she was well aware of how hospitals should work—and how they often don’t work. After seven years as a hospital administrator, she went to graduate school for a master’s degree in public health, then spent 12 years as executive director for Planetree Health Resource Center, San Francisco, a nonprofit consumer healthcare organization that focuses on patient-centered care. While Orr was with Planetree the organization created a revolutionary demonstration project that brought patient-centered care to three model sites. The project centered on changing the hospitals’ physical environments as well as providing patients access to their own medical records.

Approximately 12 years ago, Orr left Planetree to start her own consulting practice. The Robin Orr Group (Santa Barbara, Calif.) works with healthcare organizations to effect patient-centered care. At the time she was admitted to the ED at Cottage Hospital, Orr’s consulting work was tapering off as she struggled with constant pain.

From the perspective of a health professional, I could see that a hospitalist helps eliminate waste. I know that hospital resources are so precious, and when someone can help expedite a procedure or test, it’s extremely valuable.

—Robin Orr

Enter the Hospitalist

At 7 a.m. on the Saturday the morning after Orr was admitted, Eric Trautwein, MD, checked on her. Dr. Trautwein is a hospitalist with the Samsun Santa Barbara Medical Foundation, which employs approximately 200 physicians in multiple specialties.

“Eric was a breathe of fresh air,” says Cook. “He … had read all her charts and immediately asked about the pain and got it under control.” Throughout the ordeal, Cook says “everyone would ask Robin what the pain level was, and she’d say ‘11,’ and they’d write it down. Eric did something about it.”

The next step, as Cook recalls, was a thorough examination. “I’ll never forget—he noticed that one knee reflex had a very subtle difference,” she says. “He wanted to double check that, saying he never made assumptions. He immediately got tests scheduled for that day, which was a Saturday. That never happens.”

Orr was scheduled for an immediate CAT scan, PET scan, and MRI. The results were available by Monday: The tests showed a mass of 4.5 x 3 cm to the left retroperitoneum adjacent to the aorta, consistent with metastatic disease.

After months of dealing with healthcare professionals who focused on and treated Orr’s pain, both Orr and Cook believe that the hospitalist’s diligence in performing a thorough exam and insistence on immediate tests were remarkable.

“A hospitalist saved my life,” Orr says confidently.

Dr. Trautwein doesn’t feel his exam and diagnosis were unusual.

“I’m not sure I did anything special,” he says. “I know for sure that my partners would have done the same things I did, and so would most hospitalists.”

After the Test Results

At the end of the weekend during Orr’s stay, Dr. Trautwein’s shift ended and his partner, Jeffrey Yim, MD, took over. Before the change, Dr. Trautwein assured the women that he’d go over Orr’s case with his partner, and that he would stay in touch. This is standard procedure among the hospitalists in their practice.

“We’ll ask if there’s anything they want us to convey to the new doctor” before we go off shift, says Dr. Yim.

The hospitalists at Samsun Santa Barbara Medical Foundation take great care with transitions during shift changes because they are aware that mistakes can happen if communication is incomplete.

“Hand-offs are one of our biggest challenges,” says Dr. Yim. “Ours aren’t formalized, but we follow a standard practice of leaving what we call an ‘off-service note.’ This is very comprehensive, almost like a discharge note, and includes all important details. In addition, the outgoing and incoming hospitalists have a sign-off conversation, either in person or over the phone, to cover any social issues or dynamics. With Robin, for example, pain control was an issue.”

Dr. Yim told Orr and Cook the results of the tests.

“Dr. Yim came in on Tuesday, and it was like passing a baton in an Olympic race,” recalls Cook, who is an expert and author on customer service. “Both [of the hospitalists] have empathy, [a skill that is] relevant and timely, and a sense of urgency.”

Orr agrees that Dr. Yim’s care was as helpful as Dr. Trautwein’s.

“Both hospitalists made sure I was treated as a human being; they weren’t just treating my pain,” she says. “Dr. Yim made sure I got what I needed at discharge, which was very necessary. He was on top of it and made sure it included follow-up.”

In Praise of Hospitalists

Despite her profession, Orr says she had never heard of hospitalists before meeting Dr. Trautwein. In addition to her gratitude to him for diagnosing her cancer, she was very impressed with how the role of hospitalist affected her care.

“I felt that having a hospitalist helped streamline the process,” she says. “I was admitted through the ED in the middle of a weekend night, when labs were closed and I had no access to my primary care physician. Despite the timing, there was continuity and follow-through, and there was speed of action.”

Orr was particularly impressed at how the various departments of the hospital worked together, with a hospitalist acting as her champion with all of them.

“[Eric] has a familiarity with hospital resources and knew who to call and when to call,” she says. “He passed the baton between people in such a way that I felt I would not be dropped between departments. There were great communications, and it helped with the ease of streamlining and continuity, and it certainly helped my peace of mind.

“From the perspective of a health professional, I could see that a hospitalist helps eliminate waste,” Orr continues. “I know that hospital resources are so precious, and when someone can help expedite a procedure or test, it’s extremely valuable.”

Orr had a first-hand view of how hospitalists streamline processes and influence care for individual patients. Her experience as a patient was an educational time for her, even with her substantial background working with hospitals.

The Hospitalist’s View

While Dr. Trautwein is pleased with the outcome of his assessment of Orr, he insists that he was doing his job. In fact, he believes the toughest part of being a hospitalist is not detecting hidden illnesses, but building trust.

“The biggest part of my day is communicating. I feel like I don’t have much time to establish trust with patients,” he admits. “That’s by far the hardest thing about the job. You only get one pass to go over their medical history, but you also have to build a rapport with them. It’s not easy.”

With each new patient he sees, Dr. Trautwein is aware that that person is wary of seeing a new doctor rather than their own primary care physician.

“A lot of people are skeptical when they see a new [doctor]—especially a young doctor,” he explains. “Sometimes, I’ll start by trying to talk about something unconnected with their condition, to try to connect with them as a person. Getting patients to trust you is one of the more difficult parts of the job, but it can lead to one of the greatest satisfactions.”

As a hospitalist, Dr. Trautwein has a clear view of his role versus that of a primary care physician, and sees the value in being available to hospitalized patients.

“Primary care physicians are squeezed from every direction and can’t be around their patients in the hospital all the time,” he says. “Hospitalists get the patients’ attention; it’s not hard to drop back into someone’s room. For the patient, that’s important. They see that we care about them, and we can make the face-to-face contact with them that used to be impossible.”

Dr. Trautwein makes a special effort to see each patient as often as he can, and to share information with them.

“I try to think about it from the patient’s perspective,” he says. “The major thing that patients are hungry for in a hospital is communication.”

As for his ability to get tests scheduled on a weekend, he says that Cottage Hospital “is a pretty responsive hospital in general. I don’t spend a lot of time banging my head against the wall with them. If I talk to a person directly, in person or on the phone, they’ll respond. It is unusual to have tests done on the weekend, but it was also unusual to have a patient who needs them so much.”

Dr. Trautwein understands that a normal day’s work for a physician can mean a life-changing diagnosis for a patient. Orr and Cook understand it, too, but from their perspective, a hospitalist doing his job can lead to a miracle.

Orr’s Recovery

At the time this article was written, Orr had completed a round of radiation and was recuperating as she awaits further test results. Despite her ordeal and her pain, her outlook is as positive as her praise of hospitalists. Looking back on her experience at Cottage Hospital Santa Barbara and Dr. Trautwein’s role, she says, “The outcome of all this was my peace of mind as a patient. You can’t buy that in a hospital anywhere in America today.” TH

Contributor Jane Jerrard writes the “Hospital of the Future” series for The Hospitalist.

When Robin Orr was admitted to the ED of Santa Barbara Cottage Hospital (Calif.), she brought a long history of experience with hospitals, both as a patient and in her professional life. Orr is a cancer survivor who had undergone back surgery several months earlier and had suffered from increasing back pain since the surgery. Late one Friday night in June 24, 2005, the pain was so intense that Orr’s care partner, Sue Cook, brought her to the ED. Orr was given morphine and taken to a room for the remainder of the night.

Who Is Robin Orr?

Orr was no ordinary hospital patient. With nearly three decades of experience as a healthcare professional working with hospitals, she was well aware of how hospitals should work—and how they often don’t work. After seven years as a hospital administrator, she went to graduate school for a master’s degree in public health, then spent 12 years as executive director for Planetree Health Resource Center, San Francisco, a nonprofit consumer healthcare organization that focuses on patient-centered care. While Orr was with Planetree the organization created a revolutionary demonstration project that brought patient-centered care to three model sites. The project centered on changing the hospitals’ physical environments as well as providing patients access to their own medical records.

Approximately 12 years ago, Orr left Planetree to start her own consulting practice. The Robin Orr Group (Santa Barbara, Calif.) works with healthcare organizations to effect patient-centered care. At the time she was admitted to the ED at Cottage Hospital, Orr’s consulting work was tapering off as she struggled with constant pain.

From the perspective of a health professional, I could see that a hospitalist helps eliminate waste. I know that hospital resources are so precious, and when someone can help expedite a procedure or test, it’s extremely valuable.

—Robin Orr

Enter the Hospitalist

At 7 a.m. on the Saturday the morning after Orr was admitted, Eric Trautwein, MD, checked on her. Dr. Trautwein is a hospitalist with the Samsun Santa Barbara Medical Foundation, which employs approximately 200 physicians in multiple specialties.

“Eric was a breathe of fresh air,” says Cook. “He … had read all her charts and immediately asked about the pain and got it under control.” Throughout the ordeal, Cook says “everyone would ask Robin what the pain level was, and she’d say ‘11,’ and they’d write it down. Eric did something about it.”

The next step, as Cook recalls, was a thorough examination. “I’ll never forget—he noticed that one knee reflex had a very subtle difference,” she says. “He wanted to double check that, saying he never made assumptions. He immediately got tests scheduled for that day, which was a Saturday. That never happens.”

Orr was scheduled for an immediate CAT scan, PET scan, and MRI. The results were available by Monday: The tests showed a mass of 4.5 x 3 cm to the left retroperitoneum adjacent to the aorta, consistent with metastatic disease.

After months of dealing with healthcare professionals who focused on and treated Orr’s pain, both Orr and Cook believe that the hospitalist’s diligence in performing a thorough exam and insistence on immediate tests were remarkable.

“A hospitalist saved my life,” Orr says confidently.

Dr. Trautwein doesn’t feel his exam and diagnosis were unusual.

“I’m not sure I did anything special,” he says. “I know for sure that my partners would have done the same things I did, and so would most hospitalists.”

After the Test Results

At the end of the weekend during Orr’s stay, Dr. Trautwein’s shift ended and his partner, Jeffrey Yim, MD, took over. Before the change, Dr. Trautwein assured the women that he’d go over Orr’s case with his partner, and that he would stay in touch. This is standard procedure among the hospitalists in their practice.

“We’ll ask if there’s anything they want us to convey to the new doctor” before we go off shift, says Dr. Yim.

The hospitalists at Samsun Santa Barbara Medical Foundation take great care with transitions during shift changes because they are aware that mistakes can happen if communication is incomplete.

“Hand-offs are one of our biggest challenges,” says Dr. Yim. “Ours aren’t formalized, but we follow a standard practice of leaving what we call an ‘off-service note.’ This is very comprehensive, almost like a discharge note, and includes all important details. In addition, the outgoing and incoming hospitalists have a sign-off conversation, either in person or over the phone, to cover any social issues or dynamics. With Robin, for example, pain control was an issue.”

Dr. Yim told Orr and Cook the results of the tests.

“Dr. Yim came in on Tuesday, and it was like passing a baton in an Olympic race,” recalls Cook, who is an expert and author on customer service. “Both [of the hospitalists] have empathy, [a skill that is] relevant and timely, and a sense of urgency.”

Orr agrees that Dr. Yim’s care was as helpful as Dr. Trautwein’s.

“Both hospitalists made sure I was treated as a human being; they weren’t just treating my pain,” she says. “Dr. Yim made sure I got what I needed at discharge, which was very necessary. He was on top of it and made sure it included follow-up.”

In Praise of Hospitalists

Despite her profession, Orr says she had never heard of hospitalists before meeting Dr. Trautwein. In addition to her gratitude to him for diagnosing her cancer, she was very impressed with how the role of hospitalist affected her care.

“I felt that having a hospitalist helped streamline the process,” she says. “I was admitted through the ED in the middle of a weekend night, when labs were closed and I had no access to my primary care physician. Despite the timing, there was continuity and follow-through, and there was speed of action.”

Orr was particularly impressed at how the various departments of the hospital worked together, with a hospitalist acting as her champion with all of them.

“[Eric] has a familiarity with hospital resources and knew who to call and when to call,” she says. “He passed the baton between people in such a way that I felt I would not be dropped between departments. There were great communications, and it helped with the ease of streamlining and continuity, and it certainly helped my peace of mind.

“From the perspective of a health professional, I could see that a hospitalist helps eliminate waste,” Orr continues. “I know that hospital resources are so precious, and when someone can help expedite a procedure or test, it’s extremely valuable.”

Orr had a first-hand view of how hospitalists streamline processes and influence care for individual patients. Her experience as a patient was an educational time for her, even with her substantial background working with hospitals.

The Hospitalist’s View

While Dr. Trautwein is pleased with the outcome of his assessment of Orr, he insists that he was doing his job. In fact, he believes the toughest part of being a hospitalist is not detecting hidden illnesses, but building trust.

“The biggest part of my day is communicating. I feel like I don’t have much time to establish trust with patients,” he admits. “That’s by far the hardest thing about the job. You only get one pass to go over their medical history, but you also have to build a rapport with them. It’s not easy.”

With each new patient he sees, Dr. Trautwein is aware that that person is wary of seeing a new doctor rather than their own primary care physician.

“A lot of people are skeptical when they see a new [doctor]—especially a young doctor,” he explains. “Sometimes, I’ll start by trying to talk about something unconnected with their condition, to try to connect with them as a person. Getting patients to trust you is one of the more difficult parts of the job, but it can lead to one of the greatest satisfactions.”

As a hospitalist, Dr. Trautwein has a clear view of his role versus that of a primary care physician, and sees the value in being available to hospitalized patients.

“Primary care physicians are squeezed from every direction and can’t be around their patients in the hospital all the time,” he says. “Hospitalists get the patients’ attention; it’s not hard to drop back into someone’s room. For the patient, that’s important. They see that we care about them, and we can make the face-to-face contact with them that used to be impossible.”

Dr. Trautwein makes a special effort to see each patient as often as he can, and to share information with them.

“I try to think about it from the patient’s perspective,” he says. “The major thing that patients are hungry for in a hospital is communication.”

As for his ability to get tests scheduled on a weekend, he says that Cottage Hospital “is a pretty responsive hospital in general. I don’t spend a lot of time banging my head against the wall with them. If I talk to a person directly, in person or on the phone, they’ll respond. It is unusual to have tests done on the weekend, but it was also unusual to have a patient who needs them so much.”

Dr. Trautwein understands that a normal day’s work for a physician can mean a life-changing diagnosis for a patient. Orr and Cook understand it, too, but from their perspective, a hospitalist doing his job can lead to a miracle.

Orr’s Recovery

At the time this article was written, Orr had completed a round of radiation and was recuperating as she awaits further test results. Despite her ordeal and her pain, her outlook is as positive as her praise of hospitalists. Looking back on her experience at Cottage Hospital Santa Barbara and Dr. Trautwein’s role, she says, “The outcome of all this was my peace of mind as a patient. You can’t buy that in a hospital anywhere in America today.” TH

Contributor Jane Jerrard writes the “Hospital of the Future” series for The Hospitalist.

When Robin Orr was admitted to the ED of Santa Barbara Cottage Hospital (Calif.), she brought a long history of experience with hospitals, both as a patient and in her professional life. Orr is a cancer survivor who had undergone back surgery several months earlier and had suffered from increasing back pain since the surgery. Late one Friday night in June 24, 2005, the pain was so intense that Orr’s care partner, Sue Cook, brought her to the ED. Orr was given morphine and taken to a room for the remainder of the night.

Who Is Robin Orr?

Orr was no ordinary hospital patient. With nearly three decades of experience as a healthcare professional working with hospitals, she was well aware of how hospitals should work—and how they often don’t work. After seven years as a hospital administrator, she went to graduate school for a master’s degree in public health, then spent 12 years as executive director for Planetree Health Resource Center, San Francisco, a nonprofit consumer healthcare organization that focuses on patient-centered care. While Orr was with Planetree the organization created a revolutionary demonstration project that brought patient-centered care to three model sites. The project centered on changing the hospitals’ physical environments as well as providing patients access to their own medical records.

Approximately 12 years ago, Orr left Planetree to start her own consulting practice. The Robin Orr Group (Santa Barbara, Calif.) works with healthcare organizations to effect patient-centered care. At the time she was admitted to the ED at Cottage Hospital, Orr’s consulting work was tapering off as she struggled with constant pain.

From the perspective of a health professional, I could see that a hospitalist helps eliminate waste. I know that hospital resources are so precious, and when someone can help expedite a procedure or test, it’s extremely valuable.

—Robin Orr

Enter the Hospitalist

At 7 a.m. on the Saturday the morning after Orr was admitted, Eric Trautwein, MD, checked on her. Dr. Trautwein is a hospitalist with the Samsun Santa Barbara Medical Foundation, which employs approximately 200 physicians in multiple specialties.

“Eric was a breathe of fresh air,” says Cook. “He … had read all her charts and immediately asked about the pain and got it under control.” Throughout the ordeal, Cook says “everyone would ask Robin what the pain level was, and she’d say ‘11,’ and they’d write it down. Eric did something about it.”

The next step, as Cook recalls, was a thorough examination. “I’ll never forget—he noticed that one knee reflex had a very subtle difference,” she says. “He wanted to double check that, saying he never made assumptions. He immediately got tests scheduled for that day, which was a Saturday. That never happens.”

Orr was scheduled for an immediate CAT scan, PET scan, and MRI. The results were available by Monday: The tests showed a mass of 4.5 x 3 cm to the left retroperitoneum adjacent to the aorta, consistent with metastatic disease.

After months of dealing with healthcare professionals who focused on and treated Orr’s pain, both Orr and Cook believe that the hospitalist’s diligence in performing a thorough exam and insistence on immediate tests were remarkable.

“A hospitalist saved my life,” Orr says confidently.

Dr. Trautwein doesn’t feel his exam and diagnosis were unusual.

“I’m not sure I did anything special,” he says. “I know for sure that my partners would have done the same things I did, and so would most hospitalists.”

After the Test Results

At the end of the weekend during Orr’s stay, Dr. Trautwein’s shift ended and his partner, Jeffrey Yim, MD, took over. Before the change, Dr. Trautwein assured the women that he’d go over Orr’s case with his partner, and that he would stay in touch. This is standard procedure among the hospitalists in their practice.

“We’ll ask if there’s anything they want us to convey to the new doctor” before we go off shift, says Dr. Yim.

The hospitalists at Samsun Santa Barbara Medical Foundation take great care with transitions during shift changes because they are aware that mistakes can happen if communication is incomplete.

“Hand-offs are one of our biggest challenges,” says Dr. Yim. “Ours aren’t formalized, but we follow a standard practice of leaving what we call an ‘off-service note.’ This is very comprehensive, almost like a discharge note, and includes all important details. In addition, the outgoing and incoming hospitalists have a sign-off conversation, either in person or over the phone, to cover any social issues or dynamics. With Robin, for example, pain control was an issue.”

Dr. Yim told Orr and Cook the results of the tests.

“Dr. Yim came in on Tuesday, and it was like passing a baton in an Olympic race,” recalls Cook, who is an expert and author on customer service. “Both [of the hospitalists] have empathy, [a skill that is] relevant and timely, and a sense of urgency.”

Orr agrees that Dr. Yim’s care was as helpful as Dr. Trautwein’s.

“Both hospitalists made sure I was treated as a human being; they weren’t just treating my pain,” she says. “Dr. Yim made sure I got what I needed at discharge, which was very necessary. He was on top of it and made sure it included follow-up.”

In Praise of Hospitalists

Despite her profession, Orr says she had never heard of hospitalists before meeting Dr. Trautwein. In addition to her gratitude to him for diagnosing her cancer, she was very impressed with how the role of hospitalist affected her care.

“I felt that having a hospitalist helped streamline the process,” she says. “I was admitted through the ED in the middle of a weekend night, when labs were closed and I had no access to my primary care physician. Despite the timing, there was continuity and follow-through, and there was speed of action.”

Orr was particularly impressed at how the various departments of the hospital worked together, with a hospitalist acting as her champion with all of them.

“[Eric] has a familiarity with hospital resources and knew who to call and when to call,” she says. “He passed the baton between people in such a way that I felt I would not be dropped between departments. There were great communications, and it helped with the ease of streamlining and continuity, and it certainly helped my peace of mind.

“From the perspective of a health professional, I could see that a hospitalist helps eliminate waste,” Orr continues. “I know that hospital resources are so precious, and when someone can help expedite a procedure or test, it’s extremely valuable.”

Orr had a first-hand view of how hospitalists streamline processes and influence care for individual patients. Her experience as a patient was an educational time for her, even with her substantial background working with hospitals.

The Hospitalist’s View

While Dr. Trautwein is pleased with the outcome of his assessment of Orr, he insists that he was doing his job. In fact, he believes the toughest part of being a hospitalist is not detecting hidden illnesses, but building trust.

“The biggest part of my day is communicating. I feel like I don’t have much time to establish trust with patients,” he admits. “That’s by far the hardest thing about the job. You only get one pass to go over their medical history, but you also have to build a rapport with them. It’s not easy.”

With each new patient he sees, Dr. Trautwein is aware that that person is wary of seeing a new doctor rather than their own primary care physician.

“A lot of people are skeptical when they see a new [doctor]—especially a young doctor,” he explains. “Sometimes, I’ll start by trying to talk about something unconnected with their condition, to try to connect with them as a person. Getting patients to trust you is one of the more difficult parts of the job, but it can lead to one of the greatest satisfactions.”

As a hospitalist, Dr. Trautwein has a clear view of his role versus that of a primary care physician, and sees the value in being available to hospitalized patients.

“Primary care physicians are squeezed from every direction and can’t be around their patients in the hospital all the time,” he says. “Hospitalists get the patients’ attention; it’s not hard to drop back into someone’s room. For the patient, that’s important. They see that we care about them, and we can make the face-to-face contact with them that used to be impossible.”

Dr. Trautwein makes a special effort to see each patient as often as he can, and to share information with them.

“I try to think about it from the patient’s perspective,” he says. “The major thing that patients are hungry for in a hospital is communication.”

As for his ability to get tests scheduled on a weekend, he says that Cottage Hospital “is a pretty responsive hospital in general. I don’t spend a lot of time banging my head against the wall with them. If I talk to a person directly, in person or on the phone, they’ll respond. It is unusual to have tests done on the weekend, but it was also unusual to have a patient who needs them so much.”

Dr. Trautwein understands that a normal day’s work for a physician can mean a life-changing diagnosis for a patient. Orr and Cook understand it, too, but from their perspective, a hospitalist doing his job can lead to a miracle.

Orr’s Recovery

At the time this article was written, Orr had completed a round of radiation and was recuperating as she awaits further test results. Despite her ordeal and her pain, her outlook is as positive as her praise of hospitalists. Looking back on her experience at Cottage Hospital Santa Barbara and Dr. Trautwein’s role, she says, “The outcome of all this was my peace of mind as a patient. You can’t buy that in a hospital anywhere in America today.” TH

Contributor Jane Jerrard writes the “Hospital of the Future” series for The Hospitalist.

CHICAGO — An apparent defect in Ras signaling in lupus patients' T cells contributes to sustained expression of CD40 ligand and may provide a target to suppress disease activity, Dilrukshie Cooray, M.D., reported at the combined annual meeting of the Central Society for Clinical Research and the Midwestern section of the American Federation for Medical Research.

Previous evidence suggested that a defect in the downregulation of the Ras pathway in lupus T cells led to the failure to develop anergy and to an abnormally prolonged expression of CD40 ligand (CD40L) (Arthritis Rheum. 2001;44:397–407).

Working on that hypothesis, Dr. Cooray and colleagues performed immunocytochemistry to test freshly isolated lymphocytes from patients with SLE and healthy controls before and after inactivation of Ras with the Ras inhibitor S-farnesylthiosalicylic acid.

They found that Ras inactivation markedly decreased the level of CD40L in T cells obtained from patients with lupus but not from healthy subjects.

“Our preliminary results support the hypothesis that there is an intrinsic defect in Ras signaling in lupus patients' T cells that contributes to sustained expression of CD40L,” reported Dr. Cooray of the rheumatology department at Loma Linda (Calif.) University. “By suppressing levels of CD40L, we think we are able to suppress disease activity.”

Because the researchers tested only six patients, it's not clear what level of CD40L is necessary for suppression of disease activity.

CHICAGO — An apparent defect in Ras signaling in lupus patients' T cells contributes to sustained expression of CD40 ligand and may provide a target to suppress disease activity, Dilrukshie Cooray, M.D., reported at the combined annual meeting of the Central Society for Clinical Research and the Midwestern section of the American Federation for Medical Research.

Previous evidence suggested that a defect in the downregulation of the Ras pathway in lupus T cells led to the failure to develop anergy and to an abnormally prolonged expression of CD40 ligand (CD40L) (Arthritis Rheum. 2001;44:397–407).

Working on that hypothesis, Dr. Cooray and colleagues performed immunocytochemistry to test freshly isolated lymphocytes from patients with SLE and healthy controls before and after inactivation of Ras with the Ras inhibitor S-farnesylthiosalicylic acid.

They found that Ras inactivation markedly decreased the level of CD40L in T cells obtained from patients with lupus but not from healthy subjects.

“Our preliminary results support the hypothesis that there is an intrinsic defect in Ras signaling in lupus patients' T cells that contributes to sustained expression of CD40L,” reported Dr. Cooray of the rheumatology department at Loma Linda (Calif.) University. “By suppressing levels of CD40L, we think we are able to suppress disease activity.”

Because the researchers tested only six patients, it's not clear what level of CD40L is necessary for suppression of disease activity.

CHICAGO — An apparent defect in Ras signaling in lupus patients' T cells contributes to sustained expression of CD40 ligand and may provide a target to suppress disease activity, Dilrukshie Cooray, M.D., reported at the combined annual meeting of the Central Society for Clinical Research and the Midwestern section of the American Federation for Medical Research.

Previous evidence suggested that a defect in the downregulation of the Ras pathway in lupus T cells led to the failure to develop anergy and to an abnormally prolonged expression of CD40 ligand (CD40L) (Arthritis Rheum. 2001;44:397–407).

Working on that hypothesis, Dr. Cooray and colleagues performed immunocytochemistry to test freshly isolated lymphocytes from patients with SLE and healthy controls before and after inactivation of Ras with the Ras inhibitor S-farnesylthiosalicylic acid.

They found that Ras inactivation markedly decreased the level of CD40L in T cells obtained from patients with lupus but not from healthy subjects.

“Our preliminary results support the hypothesis that there is an intrinsic defect in Ras signaling in lupus patients' T cells that contributes to sustained expression of CD40L,” reported Dr. Cooray of the rheumatology department at Loma Linda (Calif.) University. “By suppressing levels of CD40L, we think we are able to suppress disease activity.”

Because the researchers tested only six patients, it's not clear what level of CD40L is necessary for suppression of disease activity.

BIRMINGHAM, ENGLAND — Increased understanding of the molecular mechanisms of glucocorticoids may eventually lead to the development of new agents that provide the clinical benefits without the attendant side effects that currently hamper the use of these drugs in rheumatic diseases.

It is now known that the anti-inflammatory and immunosuppressive effects of glucocorticoids primarily function via a process of negative regulation of gene expression, or transrepression, Frank Buttgereit, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

“Glucocorticoids are very lipophilic molecules and are able to penetrate the cell membrane and bind to the cytosolic glucocorticoid receptor complex, which becomes activated and moves into the nucleus where it binds to specific DNA sites,” he explained. The result is upregulation of anti-inflammatory proteins and downregulation of inflammatory molecules such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α, he said.

An example of glucocorticoid transrepression is the effect on bone metabolism. “We currently think that TNF-α and IL-1 are able to induce osteoclasts and T cells to produce RANK ligand, which binds to the RANK receptor on osteoclast precursor cells and to the RANK receptor of the osteoclast,” he said. This results in an induced maturation of precursor cells into mature, very aggressive osteoclasts responsible for bone erosion and progression of osteoporosis. Downregulation of the TNF-α and IL-1 through transrepression retards these effects, he said.

While the benefits of these drugs stem from the genomic effects of transrepression, many of the unwanted cardiovascular, endocrine, and metabolic effects are mediated by a separate genomic process known as transactivation, said Dr. Buttgereit of the department of rheumatology and clinical immunology, University Hospital of Humboldt University, Berlin. Certain enzymes involved in the development of diabetes, for example, are activated at the genomic level by glucocorticoids, and an ongoing research effort is intended to create designer glucocorticoids that preferentially induce transrepression and have little or no transactivating activity—obtaining the benefit without the adverse effects.

These agents, several of which have been developed, are known as selective glucocorticoid receptor agonists (SEGRAs). One of these compounds, AK 216348, has been shown in animal studies to have anti-inflammatory effects equivalent to those of prednisone but with fewer transactivating effects, Dr. Buttgereit said.

Drugs of a second type of compound that has been developed are known as nitric oxide glucocorticoids or nitrosteroids. These not only bind to the glucocorticoid receptor but also slowly release nitric oxide, resulting in synergistic anti-inflammatory effects. In vitro studies of a prototype nitrosteroid, NCX-1015, have suggested that, unlike prednisone, it does not activate unwanted osteoclast activity (Rheum. Dis. Clin. North. Am. 2005;31:1–17).

Further preclinical work and then clinical trials will be needed to determine if these preliminary findings hold up, Dr. Buttgereit said.

BIRMINGHAM, ENGLAND — Increased understanding of the molecular mechanisms of glucocorticoids may eventually lead to the development of new agents that provide the clinical benefits without the attendant side effects that currently hamper the use of these drugs in rheumatic diseases.

It is now known that the anti-inflammatory and immunosuppressive effects of glucocorticoids primarily function via a process of negative regulation of gene expression, or transrepression, Frank Buttgereit, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

“Glucocorticoids are very lipophilic molecules and are able to penetrate the cell membrane and bind to the cytosolic glucocorticoid receptor complex, which becomes activated and moves into the nucleus where it binds to specific DNA sites,” he explained. The result is upregulation of anti-inflammatory proteins and downregulation of inflammatory molecules such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α, he said.

An example of glucocorticoid transrepression is the effect on bone metabolism. “We currently think that TNF-α and IL-1 are able to induce osteoclasts and T cells to produce RANK ligand, which binds to the RANK receptor on osteoclast precursor cells and to the RANK receptor of the osteoclast,” he said. This results in an induced maturation of precursor cells into mature, very aggressive osteoclasts responsible for bone erosion and progression of osteoporosis. Downregulation of the TNF-α and IL-1 through transrepression retards these effects, he said.

While the benefits of these drugs stem from the genomic effects of transrepression, many of the unwanted cardiovascular, endocrine, and metabolic effects are mediated by a separate genomic process known as transactivation, said Dr. Buttgereit of the department of rheumatology and clinical immunology, University Hospital of Humboldt University, Berlin. Certain enzymes involved in the development of diabetes, for example, are activated at the genomic level by glucocorticoids, and an ongoing research effort is intended to create designer glucocorticoids that preferentially induce transrepression and have little or no transactivating activity—obtaining the benefit without the adverse effects.

These agents, several of which have been developed, are known as selective glucocorticoid receptor agonists (SEGRAs). One of these compounds, AK 216348, has been shown in animal studies to have anti-inflammatory effects equivalent to those of prednisone but with fewer transactivating effects, Dr. Buttgereit said.

Drugs of a second type of compound that has been developed are known as nitric oxide glucocorticoids or nitrosteroids. These not only bind to the glucocorticoid receptor but also slowly release nitric oxide, resulting in synergistic anti-inflammatory effects. In vitro studies of a prototype nitrosteroid, NCX-1015, have suggested that, unlike prednisone, it does not activate unwanted osteoclast activity (Rheum. Dis. Clin. North. Am. 2005;31:1–17).

Further preclinical work and then clinical trials will be needed to determine if these preliminary findings hold up, Dr. Buttgereit said.

BIRMINGHAM, ENGLAND — Increased understanding of the molecular mechanisms of glucocorticoids may eventually lead to the development of new agents that provide the clinical benefits without the attendant side effects that currently hamper the use of these drugs in rheumatic diseases.

It is now known that the anti-inflammatory and immunosuppressive effects of glucocorticoids primarily function via a process of negative regulation of gene expression, or transrepression, Frank Buttgereit, M.D., said at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

“Glucocorticoids are very lipophilic molecules and are able to penetrate the cell membrane and bind to the cytosolic glucocorticoid receptor complex, which becomes activated and moves into the nucleus where it binds to specific DNA sites,” he explained. The result is upregulation of anti-inflammatory proteins and downregulation of inflammatory molecules such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α, he said.

An example of glucocorticoid transrepression is the effect on bone metabolism. “We currently think that TNF-α and IL-1 are able to induce osteoclasts and T cells to produce RANK ligand, which binds to the RANK receptor on osteoclast precursor cells and to the RANK receptor of the osteoclast,” he said. This results in an induced maturation of precursor cells into mature, very aggressive osteoclasts responsible for bone erosion and progression of osteoporosis. Downregulation of the TNF-α and IL-1 through transrepression retards these effects, he said.

While the benefits of these drugs stem from the genomic effects of transrepression, many of the unwanted cardiovascular, endocrine, and metabolic effects are mediated by a separate genomic process known as transactivation, said Dr. Buttgereit of the department of rheumatology and clinical immunology, University Hospital of Humboldt University, Berlin. Certain enzymes involved in the development of diabetes, for example, are activated at the genomic level by glucocorticoids, and an ongoing research effort is intended to create designer glucocorticoids that preferentially induce transrepression and have little or no transactivating activity—obtaining the benefit without the adverse effects.

These agents, several of which have been developed, are known as selective glucocorticoid receptor agonists (SEGRAs). One of these compounds, AK 216348, has been shown in animal studies to have anti-inflammatory effects equivalent to those of prednisone but with fewer transactivating effects, Dr. Buttgereit said.

Drugs of a second type of compound that has been developed are known as nitric oxide glucocorticoids or nitrosteroids. These not only bind to the glucocorticoid receptor but also slowly release nitric oxide, resulting in synergistic anti-inflammatory effects. In vitro studies of a prototype nitrosteroid, NCX-1015, have suggested that, unlike prednisone, it does not activate unwanted osteoclast activity (Rheum. Dis. Clin. North. Am. 2005;31:1–17).

Further preclinical work and then clinical trials will be needed to determine if these preliminary findings hold up, Dr. Buttgereit said.

MIAMI BEACH — The off-label use of immunosuppressive agents for myasthenia gravis can significantly decrease the need for steroids, while improving symptoms.

However, compared with prednisone, other immunosuppressants are much more expensive and carry their own risks of adverse events, so their use should be carefully evaluated on a case-by-case basis, Gil Wolfe, M.D., said at the annual meeting of the American Academy of Neurology.

Since acetylcholinesterase inhibitor monotherapy controls the symptoms of no more than 40% of myasthenia gravis (MG) patients, most patients will end up taking prednisone or other immunosuppressive agents, either alone or in combination, said Dr. Wolfe, a neurologist and codirector of the Muscular Dystrophy Association clinic at the University of Texas Southwestern Medical Center in Dallas.

▸ Prednisone—started low and slowly titrated, and tapered down very slowly after symptom improvement—is the most commonly used regimen. But few patients will be able to taper off prednisone completely; the rest will require long-term, low-dose therapy. Other immunosuppressants may be added to prednisone to act as steroid-sparing agents and to assist in successful prednisone discontinuation, Dr. Wolfe said.

▸ Azathioprine is used as a steroid-sparing agent for patients who relapse during a prednisone taper and for those who have adverse events during long-term steroid use. “Up to 90% of patients respond well to [azathioprine], if they can tolerate it,” he said. “In those who can, it can reduce steroid consumption by up to 80% by 2 years.” One small study concluded that 63% of those who took azathioprine for 36 months had completely tapered off prednisone, compared with 20% of those who took prednisone alone.

The major cause for discontinuation is a flulike reaction, seen in 10%–20% of patients. The drug also has a long onset of action—maximum benefit may not be seen for up to 2 years.

▸ Cyclosporine works more rapidly, with maximum benefit seen by 3 months. Patients who are refractory to other agents may respond to cyclosporine; this drug is as effective as azathioprine in symptom improvement, judging from the findings of a recent study. However, cyclosporine is less well tolerated than azathioprine, and some studies suggest that about half of patients discontinue the medication because of adverse events.

“It's important not to mix different cyclosporine preparations, because the different brands are not bioequivalent,” Dr. Wolfe added.

▸ Mycophenolate mofetil has shown promise as the newest immunosuppressive agent commonly used for MG, he said. A recent open-label study showed that 73% of patients achieved pharmacologic remission, minimal manifestation status, or symptom improvement with mycophenolate. The drug has a rapid onset of action, with improvement seen in 9–11 weeks and maximum effect by 6 months. “You may be able to decrease steroids by up to 50% in most patients with this drug,” Dr. Wolfe said.

Mycophenolate is well tolerated. Its main adverse events are diarrhea, vomiting, increased risk of infection, and rarely, leukopenia; only about 6% of patients discontinue the drug because of an adverse event. Switching to dosing three times daily may decrease the incidence of diarrhea.

▸ Cyclophosphamide is used mainly for refractory MG patients. “This drug has a lot of potential for adverse events,” Dr. Wolfe said. “But IV pulse therapy looks like it could be safer than daily oral therapy, because there is a lower cumulative dose.” However, cyclophosphamide should be considered a third-line therapy.

▸ Intravenous gamma globulin is employed as a lower-risk alternative to plasma exchange. An analysis of eight retrospective studies indicated that 73% of patients responded well to intravenous gamma globulin, and did so very quickly—in about 4–5 days. The beneficial effects can last up to several months. “IV gamma globulin is a particularly attractive alternative to plasma exchange for patients with poor venous access, hemodynamic instability, or other contraindications to plasmapheresis,” he said.

▸ Investigational agents include tacrolimus, rituximab, and monarsen. Tacrolimus has demonstrated efficacy as a monotherapy or in combination with corticosteroids, in a few recent open trials. It has a similar mechanism of action to cyclosporine but appears less nephrotoxic. However, hyperglycemia may occur. Rituximab has been reported in just a few MG cases and was associated with substantial clinical improvement at 4 weeks and with no complications or adverse events. Monarsen is being investigated in preliminary MG studies. In an open trial of 16 patients, 15 who discontinued the antiacetylcholinesterase pyridostigmine demonstrated improvement while using monarsen.

MIAMI BEACH — The off-label use of immunosuppressive agents for myasthenia gravis can significantly decrease the need for steroids, while improving symptoms.

However, compared with prednisone, other immunosuppressants are much more expensive and carry their own risks of adverse events, so their use should be carefully evaluated on a case-by-case basis, Gil Wolfe, M.D., said at the annual meeting of the American Academy of Neurology.

Since acetylcholinesterase inhibitor monotherapy controls the symptoms of no more than 40% of myasthenia gravis (MG) patients, most patients will end up taking prednisone or other immunosuppressive agents, either alone or in combination, said Dr. Wolfe, a neurologist and codirector of the Muscular Dystrophy Association clinic at the University of Texas Southwestern Medical Center in Dallas.

▸ Prednisone—started low and slowly titrated, and tapered down very slowly after symptom improvement—is the most commonly used regimen. But few patients will be able to taper off prednisone completely; the rest will require long-term, low-dose therapy. Other immunosuppressants may be added to prednisone to act as steroid-sparing agents and to assist in successful prednisone discontinuation, Dr. Wolfe said.

▸ Azathioprine is used as a steroid-sparing agent for patients who relapse during a prednisone taper and for those who have adverse events during long-term steroid use. “Up to 90% of patients respond well to [azathioprine], if they can tolerate it,” he said. “In those who can, it can reduce steroid consumption by up to 80% by 2 years.” One small study concluded that 63% of those who took azathioprine for 36 months had completely tapered off prednisone, compared with 20% of those who took prednisone alone.

The major cause for discontinuation is a flulike reaction, seen in 10%–20% of patients. The drug also has a long onset of action—maximum benefit may not be seen for up to 2 years.

▸ Cyclosporine works more rapidly, with maximum benefit seen by 3 months. Patients who are refractory to other agents may respond to cyclosporine; this drug is as effective as azathioprine in symptom improvement, judging from the findings of a recent study. However, cyclosporine is less well tolerated than azathioprine, and some studies suggest that about half of patients discontinue the medication because of adverse events.

“It's important not to mix different cyclosporine preparations, because the different brands are not bioequivalent,” Dr. Wolfe added.

▸ Mycophenolate mofetil has shown promise as the newest immunosuppressive agent commonly used for MG, he said. A recent open-label study showed that 73% of patients achieved pharmacologic remission, minimal manifestation status, or symptom improvement with mycophenolate. The drug has a rapid onset of action, with improvement seen in 9–11 weeks and maximum effect by 6 months. “You may be able to decrease steroids by up to 50% in most patients with this drug,” Dr. Wolfe said.

Mycophenolate is well tolerated. Its main adverse events are diarrhea, vomiting, increased risk of infection, and rarely, leukopenia; only about 6% of patients discontinue the drug because of an adverse event. Switching to dosing three times daily may decrease the incidence of diarrhea.

▸ Cyclophosphamide is used mainly for refractory MG patients. “This drug has a lot of potential for adverse events,” Dr. Wolfe said. “But IV pulse therapy looks like it could be safer than daily oral therapy, because there is a lower cumulative dose.” However, cyclophosphamide should be considered a third-line therapy.

▸ Intravenous gamma globulin is employed as a lower-risk alternative to plasma exchange. An analysis of eight retrospective studies indicated that 73% of patients responded well to intravenous gamma globulin, and did so very quickly—in about 4–5 days. The beneficial effects can last up to several months. “IV gamma globulin is a particularly attractive alternative to plasma exchange for patients with poor venous access, hemodynamic instability, or other contraindications to plasmapheresis,” he said.

▸ Investigational agents include tacrolimus, rituximab, and monarsen. Tacrolimus has demonstrated efficacy as a monotherapy or in combination with corticosteroids, in a few recent open trials. It has a similar mechanism of action to cyclosporine but appears less nephrotoxic. However, hyperglycemia may occur. Rituximab has been reported in just a few MG cases and was associated with substantial clinical improvement at 4 weeks and with no complications or adverse events. Monarsen is being investigated in preliminary MG studies. In an open trial of 16 patients, 15 who discontinued the antiacetylcholinesterase pyridostigmine demonstrated improvement while using monarsen.

MIAMI BEACH — The off-label use of immunosuppressive agents for myasthenia gravis can significantly decrease the need for steroids, while improving symptoms.

However, compared with prednisone, other immunosuppressants are much more expensive and carry their own risks of adverse events, so their use should be carefully evaluated on a case-by-case basis, Gil Wolfe, M.D., said at the annual meeting of the American Academy of Neurology.

Since acetylcholinesterase inhibitor monotherapy controls the symptoms of no more than 40% of myasthenia gravis (MG) patients, most patients will end up taking prednisone or other immunosuppressive agents, either alone or in combination, said Dr. Wolfe, a neurologist and codirector of the Muscular Dystrophy Association clinic at the University of Texas Southwestern Medical Center in Dallas.

▸ Prednisone—started low and slowly titrated, and tapered down very slowly after symptom improvement—is the most commonly used regimen. But few patients will be able to taper off prednisone completely; the rest will require long-term, low-dose therapy. Other immunosuppressants may be added to prednisone to act as steroid-sparing agents and to assist in successful prednisone discontinuation, Dr. Wolfe said.

▸ Azathioprine is used as a steroid-sparing agent for patients who relapse during a prednisone taper and for those who have adverse events during long-term steroid use. “Up to 90% of patients respond well to [azathioprine], if they can tolerate it,” he said. “In those who can, it can reduce steroid consumption by up to 80% by 2 years.” One small study concluded that 63% of those who took azathioprine for 36 months had completely tapered off prednisone, compared with 20% of those who took prednisone alone.

The major cause for discontinuation is a flulike reaction, seen in 10%–20% of patients. The drug also has a long onset of action—maximum benefit may not be seen for up to 2 years.

▸ Cyclosporine works more rapidly, with maximum benefit seen by 3 months. Patients who are refractory to other agents may respond to cyclosporine; this drug is as effective as azathioprine in symptom improvement, judging from the findings of a recent study. However, cyclosporine is less well tolerated than azathioprine, and some studies suggest that about half of patients discontinue the medication because of adverse events.

“It's important not to mix different cyclosporine preparations, because the different brands are not bioequivalent,” Dr. Wolfe added.

▸ Mycophenolate mofetil has shown promise as the newest immunosuppressive agent commonly used for MG, he said. A recent open-label study showed that 73% of patients achieved pharmacologic remission, minimal manifestation status, or symptom improvement with mycophenolate. The drug has a rapid onset of action, with improvement seen in 9–11 weeks and maximum effect by 6 months. “You may be able to decrease steroids by up to 50% in most patients with this drug,” Dr. Wolfe said.

Mycophenolate is well tolerated. Its main adverse events are diarrhea, vomiting, increased risk of infection, and rarely, leukopenia; only about 6% of patients discontinue the drug because of an adverse event. Switching to dosing three times daily may decrease the incidence of diarrhea.

▸ Cyclophosphamide is used mainly for refractory MG patients. “This drug has a lot of potential for adverse events,” Dr. Wolfe said. “But IV pulse therapy looks like it could be safer than daily oral therapy, because there is a lower cumulative dose.” However, cyclophosphamide should be considered a third-line therapy.

▸ Intravenous gamma globulin is employed as a lower-risk alternative to plasma exchange. An analysis of eight retrospective studies indicated that 73% of patients responded well to intravenous gamma globulin, and did so very quickly—in about 4–5 days. The beneficial effects can last up to several months. “IV gamma globulin is a particularly attractive alternative to plasma exchange for patients with poor venous access, hemodynamic instability, or other contraindications to plasmapheresis,” he said.

▸ Investigational agents include tacrolimus, rituximab, and monarsen. Tacrolimus has demonstrated efficacy as a monotherapy or in combination with corticosteroids, in a few recent open trials. It has a similar mechanism of action to cyclosporine but appears less nephrotoxic. However, hyperglycemia may occur. Rituximab has been reported in just a few MG cases and was associated with substantial clinical improvement at 4 weeks and with no complications or adverse events. Monarsen is being investigated in preliminary MG studies. In an open trial of 16 patients, 15 who discontinued the antiacetylcholinesterase pyridostigmine demonstrated improvement while using monarsen.

KEY BISCAYNE, FLA. — Although antimalarial agents are first-line treatment for cutaneous sarcoidosis, infliximab and leflunomide are showing promise and may be appropriate for refractory patients, Theodore Rosen, M.D., said at the annual meeting of the Noah Worcester Dermatological Society.

Corticosteroids and/or methotrexate are generally second-line therapy for patients who fail to respond to chloroquine or hydroxychloroquine. There are few data, however, to support the use of other drugs that researchers have considered—pentoxifylline, tetracyclines, or isotretinoin, “which we can barely give right now,” Dr. Rosen said.

Sarcoidosis occurs 10–20 times more often in black patients, particularly women, and is associated with a mortality rate 15 times greater in blacks than in whites. The condition is rare in patients younger than 4 years, and the peak incidence is between age 20 and 40 years. When there is skin involvement, it suggests a chronic condition with lung and bone involvement. Sarcoidosis is fatal in 5%–10% of cases.

Diagnosis can be challenging. Skin presentations are polymorphic, and include lesions that are lupus pernio, annular, psoriasiform, ichthyosis-like, verrucous, ulcerative, hypopigmented, nodular, or micropapular. “Any skin lesion not otherwise diagnosed should suggest sarcoidosis,” said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

Treatments are aimed at interrupting the immunopathogenesis at various stages. For example, 4 mg/kg per day of chloroquine or 6.5 mg/kg per day of hydroxychloroquine can inhibit antigen presentation. Topical or oral corticosteroids, including 40–80 mg/day of oral prednisone, can suppress granuloma formation. An immunosuppressive agent, such as methotrexate, 30 mg weekly, is another option.

Tumor necrosis factor α (TNF-α) agents also suppress granuloma formation. Infliximab [Remicade] is “where I'm putting my money,” Dr. Rosen said. Infliximab appears to offer excellent control, but there are risk and cost considerations, he said. The Food and Drug Administration approved the TNF-α antibody for Crohn's disease and rheumatoid arthritis. For sarcoidosis, Dr. Rosen suggested a dosing regimen of 3–10 mg/kg per dose delivered by intravenous infusion at 0, 2, and 6 weeks, and then as dictated.

Several studies have shown that infliximab provides a “dramatic and rapid response” for cutaneous lesions, Dr. Rosen said (J. Am. Acad. Dermatol. 2003;48:290–3; J. Drugs Dermatol. 2003;2:413–4; Chest 2003;124:2028–31; and Arthritis Rheum. 2003;48:3542–3).

He also cited a woman he treated for cutaneous sarcoidosis. She failed treatment with chloroquine and hydroxychloroquine at maximal doses. She also failed treatment with prednisone as well as methotrexate; nor did she show any response to potent topical steroids. Intralesional steroids provided minimal improvement. She tried pentoxifylline and tetracycline regimens, again with no clinical improvement. However, after receiving infliximab 5 mg/kg IV at 0, 2, and 6 weeks, the prominent lesions on her face disappeared.

Long-term safety, possible induction of lymphoma, and risk of infection are concerns with infliximab. Dr. Rosen stressed that physicians must ensure the diagnosis is sarcoidosis and not TB. Cost is another factor with infliximab. He estimated the cost per infusion is $4,500–$9,000.

Leflunomide (Arava) appears promising for sarcoidosis, Dr. Rosen said. The FDA approved the agent for RA. The drug may work for this condition because it inhibits pyrimidine synthesis, decreases TNF-α response, and inhibits monocyte activation by proliferating T cells. A case series of 32 patients with skin, eye, and/or lung involvement showed 80% responded to leflunomide (Sarcoidosis Vasc. Diffuse Lung Dis. 2004;21:43–8). Nausea, headache, hypersensitivity reactions, and hepatic injury are concerns with leflunomide (Dermatology 2003;207:386–9).

KEY BISCAYNE, FLA. — Although antimalarial agents are first-line treatment for cutaneous sarcoidosis, infliximab and leflunomide are showing promise and may be appropriate for refractory patients, Theodore Rosen, M.D., said at the annual meeting of the Noah Worcester Dermatological Society.

Corticosteroids and/or methotrexate are generally second-line therapy for patients who fail to respond to chloroquine or hydroxychloroquine. There are few data, however, to support the use of other drugs that researchers have considered—pentoxifylline, tetracyclines, or isotretinoin, “which we can barely give right now,” Dr. Rosen said.

Sarcoidosis occurs 10–20 times more often in black patients, particularly women, and is associated with a mortality rate 15 times greater in blacks than in whites. The condition is rare in patients younger than 4 years, and the peak incidence is between age 20 and 40 years. When there is skin involvement, it suggests a chronic condition with lung and bone involvement. Sarcoidosis is fatal in 5%–10% of cases.

Diagnosis can be challenging. Skin presentations are polymorphic, and include lesions that are lupus pernio, annular, psoriasiform, ichthyosis-like, verrucous, ulcerative, hypopigmented, nodular, or micropapular. “Any skin lesion not otherwise diagnosed should suggest sarcoidosis,” said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

Treatments are aimed at interrupting the immunopathogenesis at various stages. For example, 4 mg/kg per day of chloroquine or 6.5 mg/kg per day of hydroxychloroquine can inhibit antigen presentation. Topical or oral corticosteroids, including 40–80 mg/day of oral prednisone, can suppress granuloma formation. An immunosuppressive agent, such as methotrexate, 30 mg weekly, is another option.

Tumor necrosis factor α (TNF-α) agents also suppress granuloma formation. Infliximab [Remicade] is “where I'm putting my money,” Dr. Rosen said. Infliximab appears to offer excellent control, but there are risk and cost considerations, he said. The Food and Drug Administration approved the TNF-α antibody for Crohn's disease and rheumatoid arthritis. For sarcoidosis, Dr. Rosen suggested a dosing regimen of 3–10 mg/kg per dose delivered by intravenous infusion at 0, 2, and 6 weeks, and then as dictated.

Several studies have shown that infliximab provides a “dramatic and rapid response” for cutaneous lesions, Dr. Rosen said (J. Am. Acad. Dermatol. 2003;48:290–3; J. Drugs Dermatol. 2003;2:413–4; Chest 2003;124:2028–31; and Arthritis Rheum. 2003;48:3542–3).

He also cited a woman he treated for cutaneous sarcoidosis. She failed treatment with chloroquine and hydroxychloroquine at maximal doses. She also failed treatment with prednisone as well as methotrexate; nor did she show any response to potent topical steroids. Intralesional steroids provided minimal improvement. She tried pentoxifylline and tetracycline regimens, again with no clinical improvement. However, after receiving infliximab 5 mg/kg IV at 0, 2, and 6 weeks, the prominent lesions on her face disappeared.

Long-term safety, possible induction of lymphoma, and risk of infection are concerns with infliximab. Dr. Rosen stressed that physicians must ensure the diagnosis is sarcoidosis and not TB. Cost is another factor with infliximab. He estimated the cost per infusion is $4,500–$9,000.

Leflunomide (Arava) appears promising for sarcoidosis, Dr. Rosen said. The FDA approved the agent for RA. The drug may work for this condition because it inhibits pyrimidine synthesis, decreases TNF-α response, and inhibits monocyte activation by proliferating T cells. A case series of 32 patients with skin, eye, and/or lung involvement showed 80% responded to leflunomide (Sarcoidosis Vasc. Diffuse Lung Dis. 2004;21:43–8). Nausea, headache, hypersensitivity reactions, and hepatic injury are concerns with leflunomide (Dermatology 2003;207:386–9).

KEY BISCAYNE, FLA. — Although antimalarial agents are first-line treatment for cutaneous sarcoidosis, infliximab and leflunomide are showing promise and may be appropriate for refractory patients, Theodore Rosen, M.D., said at the annual meeting of the Noah Worcester Dermatological Society.

Corticosteroids and/or methotrexate are generally second-line therapy for patients who fail to respond to chloroquine or hydroxychloroquine. There are few data, however, to support the use of other drugs that researchers have considered—pentoxifylline, tetracyclines, or isotretinoin, “which we can barely give right now,” Dr. Rosen said.

Sarcoidosis occurs 10–20 times more often in black patients, particularly women, and is associated with a mortality rate 15 times greater in blacks than in whites. The condition is rare in patients younger than 4 years, and the peak incidence is between age 20 and 40 years. When there is skin involvement, it suggests a chronic condition with lung and bone involvement. Sarcoidosis is fatal in 5%–10% of cases.

Diagnosis can be challenging. Skin presentations are polymorphic, and include lesions that are lupus pernio, annular, psoriasiform, ichthyosis-like, verrucous, ulcerative, hypopigmented, nodular, or micropapular. “Any skin lesion not otherwise diagnosed should suggest sarcoidosis,” said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

Treatments are aimed at interrupting the immunopathogenesis at various stages. For example, 4 mg/kg per day of chloroquine or 6.5 mg/kg per day of hydroxychloroquine can inhibit antigen presentation. Topical or oral corticosteroids, including 40–80 mg/day of oral prednisone, can suppress granuloma formation. An immunosuppressive agent, such as methotrexate, 30 mg weekly, is another option.

Tumor necrosis factor α (TNF-α) agents also suppress granuloma formation. Infliximab [Remicade] is “where I'm putting my money,” Dr. Rosen said. Infliximab appears to offer excellent control, but there are risk and cost considerations, he said. The Food and Drug Administration approved the TNF-α antibody for Crohn's disease and rheumatoid arthritis. For sarcoidosis, Dr. Rosen suggested a dosing regimen of 3–10 mg/kg per dose delivered by intravenous infusion at 0, 2, and 6 weeks, and then as dictated.

Several studies have shown that infliximab provides a “dramatic and rapid response” for cutaneous lesions, Dr. Rosen said (J. Am. Acad. Dermatol. 2003;48:290–3; J. Drugs Dermatol. 2003;2:413–4; Chest 2003;124:2028–31; and Arthritis Rheum. 2003;48:3542–3).

He also cited a woman he treated for cutaneous sarcoidosis. She failed treatment with chloroquine and hydroxychloroquine at maximal doses. She also failed treatment with prednisone as well as methotrexate; nor did she show any response to potent topical steroids. Intralesional steroids provided minimal improvement. She tried pentoxifylline and tetracycline regimens, again with no clinical improvement. However, after receiving infliximab 5 mg/kg IV at 0, 2, and 6 weeks, the prominent lesions on her face disappeared.

Long-term safety, possible induction of lymphoma, and risk of infection are concerns with infliximab. Dr. Rosen stressed that physicians must ensure the diagnosis is sarcoidosis and not TB. Cost is another factor with infliximab. He estimated the cost per infusion is $4,500–$9,000.

Leflunomide (Arava) appears promising for sarcoidosis, Dr. Rosen said. The FDA approved the agent for RA. The drug may work for this condition because it inhibits pyrimidine synthesis, decreases TNF-α response, and inhibits monocyte activation by proliferating T cells. A case series of 32 patients with skin, eye, and/or lung involvement showed 80% responded to leflunomide (Sarcoidosis Vasc. Diffuse Lung Dis. 2004;21:43–8). Nausea, headache, hypersensitivity reactions, and hepatic injury are concerns with leflunomide (Dermatology 2003;207:386–9).

BIRMINGHAM, ENGLAND — Patients with lupus who have high levels of proinflammatory high-density lipoprotein may be at particular risk for atherosclerosis and therefore could be suitable candidates for prophylactic treatment, Bevra Hahn, M.D., said at a joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Recognition of the prevalence and lethality of atherosclerosis in systemic lupus erythematosus (SLE) has led to increased interest in strategies to prevent its onset and progression, such as with statin therapy.

“We know that 30%–40% of lupus patients have carotid plaque, coronary artery calcifications, or some other manifestation of atherosclerosis, but we found that only 15% of patients in our cohort had any lipid abnormalities, so it didn't seem very reasonable to just put them all on statins,” said Dr. Hahn, professor of medicine and chief of rheumatology, at the University of California, Los Angeles.

Caution also is needed because the statin drugs have been reported to induce lupus-like syndromes with the development of antinuclear antibodies in an increasing number of patients. Statins also might aggravate lupus itself, possibly through enhancing the shift from a Th1 to Th2 immune response, which heightens B cell reactivity and increases the production of pathogenic autoantibodies (Lupus 2005;14:192–6).

So Dr. Hahn and her colleagues began looking for a new biomarker that might provide a more targeted population for statin therapy. “We reasoned that people with a chronic inflammatory disease like lupus might have a lot of proinflammatory HDL. That turned out to be right,” Dr. Hahn said.

Proinflammatory HDL particles contain inadequate amounts of antioxidant enzymes such as paraoxonase. These components are replaced by serum amyloid and oxidation products, rendering the HDL particle incapable of its vital function of protecting LDL particles from becoming oxidized. Once oxidized, LDL contributes to the early development of carotid plaque.

In a study at her center that included 153 patients with lupus, 45% were found to have proinflammatory HDL, as did 21% of a group of 44 patients with rheumatoid arthritis.

Fewer than 5% of a healthy control group had the abnormal HDL, Dr. Hahn said.

On multivariate analysis, the presence of proinflammatory HDL was highly correlated with increases in oxidized LDL, and was also correlated with coronary artery events, hypertension, and high erythrocyte sedimentation rate (ESR).

“So it looks like we might have one biomarker that would tell us which people are predisposed to atherosclerosis and should be treated for it,” she said.

The next question is what that treatment should be. In patients who have had a myocardial infarction and have high levels of proinflammatory HDL, statins do lower the levels, but not even close to the normal range, Dr. Hahnsaid.

“My personal opinion is that statins may be helpful but, if we are right about what is important in lupus atherogenesis, they won't be enough. I think the most effective therapy will be one that actually suppresses SLE activity,” she said.

BIRMINGHAM, ENGLAND — Patients with lupus who have high levels of proinflammatory high-density lipoprotein may be at particular risk for atherosclerosis and therefore could be suitable candidates for prophylactic treatment, Bevra Hahn, M.D., said at a joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Recognition of the prevalence and lethality of atherosclerosis in systemic lupus erythematosus (SLE) has led to increased interest in strategies to prevent its onset and progression, such as with statin therapy.

“We know that 30%–40% of lupus patients have carotid plaque, coronary artery calcifications, or some other manifestation of atherosclerosis, but we found that only 15% of patients in our cohort had any lipid abnormalities, so it didn't seem very reasonable to just put them all on statins,” said Dr. Hahn, professor of medicine and chief of rheumatology, at the University of California, Los Angeles.

Caution also is needed because the statin drugs have been reported to induce lupus-like syndromes with the development of antinuclear antibodies in an increasing number of patients. Statins also might aggravate lupus itself, possibly through enhancing the shift from a Th1 to Th2 immune response, which heightens B cell reactivity and increases the production of pathogenic autoantibodies (Lupus 2005;14:192–6).

So Dr. Hahn and her colleagues began looking for a new biomarker that might provide a more targeted population for statin therapy. “We reasoned that people with a chronic inflammatory disease like lupus might have a lot of proinflammatory HDL. That turned out to be right,” Dr. Hahn said.

Proinflammatory HDL particles contain inadequate amounts of antioxidant enzymes such as paraoxonase. These components are replaced by serum amyloid and oxidation products, rendering the HDL particle incapable of its vital function of protecting LDL particles from becoming oxidized. Once oxidized, LDL contributes to the early development of carotid plaque.

In a study at her center that included 153 patients with lupus, 45% were found to have proinflammatory HDL, as did 21% of a group of 44 patients with rheumatoid arthritis.

Fewer than 5% of a healthy control group had the abnormal HDL, Dr. Hahn said.

On multivariate analysis, the presence of proinflammatory HDL was highly correlated with increases in oxidized LDL, and was also correlated with coronary artery events, hypertension, and high erythrocyte sedimentation rate (ESR).

“So it looks like we might have one biomarker that would tell us which people are predisposed to atherosclerosis and should be treated for it,” she said.

The next question is what that treatment should be. In patients who have had a myocardial infarction and have high levels of proinflammatory HDL, statins do lower the levels, but not even close to the normal range, Dr. Hahnsaid.

“My personal opinion is that statins may be helpful but, if we are right about what is important in lupus atherogenesis, they won't be enough. I think the most effective therapy will be one that actually suppresses SLE activity,” she said.

BIRMINGHAM, ENGLAND — Patients with lupus who have high levels of proinflammatory high-density lipoprotein may be at particular risk for atherosclerosis and therefore could be suitable candidates for prophylactic treatment, Bevra Hahn, M.D., said at a joint meeting of the British Society for Rheumatology and the German Society for Rheumatology.

Recognition of the prevalence and lethality of atherosclerosis in systemic lupus erythematosus (SLE) has led to increased interest in strategies to prevent its onset and progression, such as with statin therapy.

“We know that 30%–40% of lupus patients have carotid plaque, coronary artery calcifications, or some other manifestation of atherosclerosis, but we found that only 15% of patients in our cohort had any lipid abnormalities, so it didn't seem very reasonable to just put them all on statins,” said Dr. Hahn, professor of medicine and chief of rheumatology, at the University of California, Los Angeles.

Caution also is needed because the statin drugs have been reported to induce lupus-like syndromes with the development of antinuclear antibodies in an increasing number of patients. Statins also might aggravate lupus itself, possibly through enhancing the shift from a Th1 to Th2 immune response, which heightens B cell reactivity and increases the production of pathogenic autoantibodies (Lupus 2005;14:192–6).

So Dr. Hahn and her colleagues began looking for a new biomarker that might provide a more targeted population for statin therapy. “We reasoned that people with a chronic inflammatory disease like lupus might have a lot of proinflammatory HDL. That turned out to be right,” Dr. Hahn said.

Proinflammatory HDL particles contain inadequate amounts of antioxidant enzymes such as paraoxonase. These components are replaced by serum amyloid and oxidation products, rendering the HDL particle incapable of its vital function of protecting LDL particles from becoming oxidized. Once oxidized, LDL contributes to the early development of carotid plaque.

In a study at her center that included 153 patients with lupus, 45% were found to have proinflammatory HDL, as did 21% of a group of 44 patients with rheumatoid arthritis.

Fewer than 5% of a healthy control group had the abnormal HDL, Dr. Hahn said.

On multivariate analysis, the presence of proinflammatory HDL was highly correlated with increases in oxidized LDL, and was also correlated with coronary artery events, hypertension, and high erythrocyte sedimentation rate (ESR).

“So it looks like we might have one biomarker that would tell us which people are predisposed to atherosclerosis and should be treated for it,” she said.

The next question is what that treatment should be. In patients who have had a myocardial infarction and have high levels of proinflammatory HDL, statins do lower the levels, but not even close to the normal range, Dr. Hahnsaid.

“My personal opinion is that statins may be helpful but, if we are right about what is important in lupus atherogenesis, they won't be enough. I think the most effective therapy will be one that actually suppresses SLE activity,” she said.