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.

BIRMINGHAM, ENGLAND — Tumor necrosis factor blockade may offer a successful therapeutic alternative to high-dose corticosteroids in the rare, potentially life-threatening occlusive vasculitis known as Takayasu's arteritis.

This large-vessel vasculitis typically involves the aorta and its main branches, causing stenosis or even obstruction. It occurs most commonly in young women.

In a case report presented at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology by Lucy E. Coates, M.D., of the Royal National Hospital for Rheumatic Diseases in Bath, England, a 17-year-old female patient developed severe left-sided facial pain that radiated into her neck and left arm.

Initially, the symptoms were thought to be musculoskeletal in origin, and she was treated with physiotherapy, analgesics, and tricyclic antidepressants.

Subsequent investigations, however, revealed the presence of markedly elevated inflammatory markers, including a plasma viscosity of 2.41 millipascal seconds (normal range 1.50–1.70 mPa·s).

She also had microcytic anemia, and levels of immunoglobulins were raised, with IgG at 17.4 g/L, IgA at 4.2 g/L, and IgM at 3.8 g/L. Various imaging studies were done, including MRI of the brain and cervical spine and CT of the abdomen and pelvis, without result.

Two years later, a lump was discovered in her neck. On examination, she was found to have bilateral carotid bruits. Magnetic resonance angiography (MRA) results showed thickening in the wall of the right brachiocephalic artery, narrowing the vessel. The subclavian artery was narrowed at its origin and underfilled distal to its origin. This was suggestive of a proximal stenosis such as is seen in Takayasu's arteritis, Dr. Coates said.

The patient was started on prednisone and azathioprine, but 1 year later her symptoms had worsened, as had the imaging findings on repeat MRA. The decision was made to institute more aggressive therapy because of concerns that the blood vessels supplying her brain were being affected, Dr. Coates said in a poster session.

Infliximab treatment was begun, with infusions of 5 mg/kg at weeks 0, 2, 6, and 10 and then every 6 weeks.

She also continued to take azathioprine (100 mg/day) and prednisone (20 mg/day). Symptomatic improvement was immediate, and another MRA the following year showed significant improvement in the caliber and appearance of the aortic arch vessels.

“Anti-TNF therapy appears to offer a promising alternative in Takayasu's arteritis, particularly if other forms of immunosuppression fail to control progression,” Dr. Coates said in her poster presentation.

Her findings support those seen in another recent series in which 14 of 15 patients with the condition responded and 10 experienced sustained remission and were able to discontinue glucocorticoid therapy (Arthritis Rheum. 2004;50:2296–304).

BIRMINGHAM, ENGLAND — Tumor necrosis factor blockade may offer a successful therapeutic alternative to high-dose corticosteroids in the rare, potentially life-threatening occlusive vasculitis known as Takayasu's arteritis.

This large-vessel vasculitis typically involves the aorta and its main branches, causing stenosis or even obstruction. It occurs most commonly in young women.

In a case report presented at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology by Lucy E. Coates, M.D., of the Royal National Hospital for Rheumatic Diseases in Bath, England, a 17-year-old female patient developed severe left-sided facial pain that radiated into her neck and left arm.

Initially, the symptoms were thought to be musculoskeletal in origin, and she was treated with physiotherapy, analgesics, and tricyclic antidepressants.

Subsequent investigations, however, revealed the presence of markedly elevated inflammatory markers, including a plasma viscosity of 2.41 millipascal seconds (normal range 1.50–1.70 mPa·s).

She also had microcytic anemia, and levels of immunoglobulins were raised, with IgG at 17.4 g/L, IgA at 4.2 g/L, and IgM at 3.8 g/L. Various imaging studies were done, including MRI of the brain and cervical spine and CT of the abdomen and pelvis, without result.

Two years later, a lump was discovered in her neck. On examination, she was found to have bilateral carotid bruits. Magnetic resonance angiography (MRA) results showed thickening in the wall of the right brachiocephalic artery, narrowing the vessel. The subclavian artery was narrowed at its origin and underfilled distal to its origin. This was suggestive of a proximal stenosis such as is seen in Takayasu's arteritis, Dr. Coates said.

The patient was started on prednisone and azathioprine, but 1 year later her symptoms had worsened, as had the imaging findings on repeat MRA. The decision was made to institute more aggressive therapy because of concerns that the blood vessels supplying her brain were being affected, Dr. Coates said in a poster session.

Infliximab treatment was begun, with infusions of 5 mg/kg at weeks 0, 2, 6, and 10 and then every 6 weeks.

She also continued to take azathioprine (100 mg/day) and prednisone (20 mg/day). Symptomatic improvement was immediate, and another MRA the following year showed significant improvement in the caliber and appearance of the aortic arch vessels.

“Anti-TNF therapy appears to offer a promising alternative in Takayasu's arteritis, particularly if other forms of immunosuppression fail to control progression,” Dr. Coates said in her poster presentation.

Her findings support those seen in another recent series in which 14 of 15 patients with the condition responded and 10 experienced sustained remission and were able to discontinue glucocorticoid therapy (Arthritis Rheum. 2004;50:2296–304).

BIRMINGHAM, ENGLAND — Tumor necrosis factor blockade may offer a successful therapeutic alternative to high-dose corticosteroids in the rare, potentially life-threatening occlusive vasculitis known as Takayasu's arteritis.

This large-vessel vasculitis typically involves the aorta and its main branches, causing stenosis or even obstruction. It occurs most commonly in young women.

In a case report presented at the joint meeting of the British Society for Rheumatology and the German Society for Rheumatology by Lucy E. Coates, M.D., of the Royal National Hospital for Rheumatic Diseases in Bath, England, a 17-year-old female patient developed severe left-sided facial pain that radiated into her neck and left arm.

Initially, the symptoms were thought to be musculoskeletal in origin, and she was treated with physiotherapy, analgesics, and tricyclic antidepressants.

Subsequent investigations, however, revealed the presence of markedly elevated inflammatory markers, including a plasma viscosity of 2.41 millipascal seconds (normal range 1.50–1.70 mPa·s).

She also had microcytic anemia, and levels of immunoglobulins were raised, with IgG at 17.4 g/L, IgA at 4.2 g/L, and IgM at 3.8 g/L. Various imaging studies were done, including MRI of the brain and cervical spine and CT of the abdomen and pelvis, without result.

Two years later, a lump was discovered in her neck. On examination, she was found to have bilateral carotid bruits. Magnetic resonance angiography (MRA) results showed thickening in the wall of the right brachiocephalic artery, narrowing the vessel. The subclavian artery was narrowed at its origin and underfilled distal to its origin. This was suggestive of a proximal stenosis such as is seen in Takayasu's arteritis, Dr. Coates said.

The patient was started on prednisone and azathioprine, but 1 year later her symptoms had worsened, as had the imaging findings on repeat MRA. The decision was made to institute more aggressive therapy because of concerns that the blood vessels supplying her brain were being affected, Dr. Coates said in a poster session.

Infliximab treatment was begun, with infusions of 5 mg/kg at weeks 0, 2, 6, and 10 and then every 6 weeks.

She also continued to take azathioprine (100 mg/day) and prednisone (20 mg/day). Symptomatic improvement was immediate, and another MRA the following year showed significant improvement in the caliber and appearance of the aortic arch vessels.

“Anti-TNF therapy appears to offer a promising alternative in Takayasu's arteritis, particularly if other forms of immunosuppression fail to control progression,” Dr. Coates said in her poster presentation.

Her findings support those seen in another recent series in which 14 of 15 patients with the condition responded and 10 experienced sustained remission and were able to discontinue glucocorticoid therapy (Arthritis Rheum. 2004;50:2296–304).