Nancy Walsh

SORRENTO, ITALY — Rituximab may provide a therapeutic option for patients with refractory, potentially life-threatening autoimmune vasculitic conditions that do not respond to conventional therapies or when dose-limiting toxicity occurs, Dr. Dario Roccatello said at the Fifth International Congress on Autoimmunity.

Although prognosis in the once rapidly fatal systemic vasculitides improved following the introduction of treatment with corticosteroids and cyclophosphamide, approximately one-fourth of patients cannot tolerate the associated side effects, and many relapse. Recent interest in the long-term management of these disorders therefore has centered on cyclophosphamide-sparing approaches, Dr. Roccatello said.

He reported on eight patients with systemic vasculitis who have been treated with this B cell-depleting agent. Their diagnoses included systemic micropolyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome. Six had kidney involvement, and necrotizing glomerulonephritis was present in four who underwent renal biopsy.

Intravenous rituximab was given in doses of 375 mg/m

Levels of the antineutrophil cytoplasmic antibodies (ANCA) that characterize these vasculitides decreased by fivefold following rituximab treatment, and one patient became ANCA-negative by week 4, said Dr. Roccatello of the University of Turin (Italy).

Treatment also resulted in significant decreases in pain and disease activity scores as measured on visual analog scales, with statistically significant decreases seen in levels of erythrocyte sedimentation rate (ESR), serum creatinine levels, proteinuria, and hematuria.

Weakness, paresthesias, arthralgias, and fever also resolved in the majority of patients.

One of the patients was a 38-year-old man who had involvement of the left carotid artery and elevations of ESR, C-reactive protein, and rheumatoid factor (RF). He was antibody positive for phospholipids and perinuclear ANCA (p-ANCA), and had symptoms including hematuria, fever, severe weakness, and paresthesia.

Initially he was treated with anticoagulants, gabapentin, and high-dose immunoglobulins, but after 2 months he had further elevations of p-ANCA and RF, as well as worsening neuropathy, and was treated with three steroid pulses and mycophenolate mofetil. One month later, he developed a leukocytic vasculitis with motor disability and underwent plasma exchange. Methotrexate was substituted for the mycophenolate mofetil, which he was not tolerating.

The patient continued to experience severe neuropathy until given rituximab. Subsequent nerve conduction studies showed resolution of the neuropathic symptoms, with amelioration in velocity, amplitude, and latency, Dr. Roccatello said.

A second patient was a 61-year-old woman who had been treated for necrotizing glomerulonephritis with corticosteroids and cylophosphamide but was referred to Dr. Roccatello's center because of persistent fever, elevated cytoplasmic ANCA (c-ANCA) levels, weight loss, dyspnea, chest pain, and sinusitis characterized by complete blockage of the maxillary sinuses.

She also had multiple nodular lesions in the superior lobes of the lungs. Treatment with rituximab resulted in a 30% decrease in the number of pulmonary lesions by week 7, and in complete clearance by 9 months. Following treatment, this patient's urinary and inflammation markers and c-ANCA levels all normalized, he said.

Dr. Roccatello also has used rituximab in severe cryoglobulinemia, which is a systemic vasculitis usually associated with hepatitis C infection and sustained by the proliferation of oligoclonal B cells. A total of 12 patients with symptomatic type II mixed cryoglobulinemia were treated with six courses of rituximab in the same dose and schedule as the eight patients with ANCA-associated vasculitides, he said.

All 12 patients had polyneuropathy and renal involvement, with 6 having biopsy-proven diffuse membranoproliferative glomerulonephritis. Five patients had bone marrow clonal restriction, and three had large necrotizing skin ulcers.

Significant decreases were seen in levels of proteinuria, ESR, and RF during 18 months of follow-up, and bone marrow abnormalities were shown to have normalized in the three patients who underwent repeat biopsy. Skin ulcers and purpura, arthralgias, weakness, paresthesias, and fever improved or resolved in all patients, Dr. Roccatello reported.

Rituximab has been used in combination regimens, such as with corticosteroids and immunosuppressants for relapsing Wegener's granulomatosis. In another series presented at the congress, Dr. Achille Aouba reported on eight patients with Wegener's granulomatosis who experienced flares or failed to respond to multiple other immunomodulatory therapies, including anti-tumor necrosis factor-α blockers.

Disease manifestations included lung nodules in four patients, orbital pseudotumor in two, and gingival hyperplasia, mononeuritis multiplex, glomerulonephritis, rectal perforation, pyoderma gangrenosum, and myocardial involvement in one each.

While continuing on corticosteroids and immunosuppressants, seven of the patients received four weekly infusions of rituximab in doses of 375 mg/m

The median Birmingham vasculitis activity score (BVAS) before rituximab treatment was 14.3, with a range of 0–30.

At 4 months, five patients had BVAS scores of zero and three were in complete remission, said Dr. Aouba of the National Reference Center for Vasculitides, Hospital Cochin, Paris, and of the French Vasculitis Study Group.

An additional three were in partial remission, with BVAS scores of zero but persistent lung nodules, and two failed to respond.

Constitutional and vasculitis-related symptoms resolved more quickly than granulomatous manifestations, which regressed slowly over several months, Dr. Aouba said.

Rituximab was well tolerated, with the only adverse event being an urticarial rash in one patient, which developed after the third infusion.

In conclusion, the addition of rituximab to conventional treatment for relapsing Wegener's granulomatosis improved clinical outcome, Dr. Aouba said.

Necrotizing skin ulcers (above) developed in association with severe mixed cryoglobulinemia. Photos courtesy Dr. Dario Roccatello

SORRENTO, ITALY — Rituximab may provide a therapeutic option for patients with refractory, potentially life-threatening autoimmune vasculitic conditions that do not respond to conventional therapies or when dose-limiting toxicity occurs, Dr. Dario Roccatello said at the Fifth International Congress on Autoimmunity.

Although prognosis in the once rapidly fatal systemic vasculitides improved following the introduction of treatment with corticosteroids and cyclophosphamide, approximately one-fourth of patients cannot tolerate the associated side effects, and many relapse. Recent interest in the long-term management of these disorders therefore has centered on cyclophosphamide-sparing approaches, Dr. Roccatello said.

He reported on eight patients with systemic vasculitis who have been treated with this B cell-depleting agent. Their diagnoses included systemic micropolyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome. Six had kidney involvement, and necrotizing glomerulonephritis was present in four who underwent renal biopsy.

Intravenous rituximab was given in doses of 375 mg/m

Levels of the antineutrophil cytoplasmic antibodies (ANCA) that characterize these vasculitides decreased by fivefold following rituximab treatment, and one patient became ANCA-negative by week 4, said Dr. Roccatello of the University of Turin (Italy).

Treatment also resulted in significant decreases in pain and disease activity scores as measured on visual analog scales, with statistically significant decreases seen in levels of erythrocyte sedimentation rate (ESR), serum creatinine levels, proteinuria, and hematuria.

Weakness, paresthesias, arthralgias, and fever also resolved in the majority of patients.

One of the patients was a 38-year-old man who had involvement of the left carotid artery and elevations of ESR, C-reactive protein, and rheumatoid factor (RF). He was antibody positive for phospholipids and perinuclear ANCA (p-ANCA), and had symptoms including hematuria, fever, severe weakness, and paresthesia.

Initially he was treated with anticoagulants, gabapentin, and high-dose immunoglobulins, but after 2 months he had further elevations of p-ANCA and RF, as well as worsening neuropathy, and was treated with three steroid pulses and mycophenolate mofetil. One month later, he developed a leukocytic vasculitis with motor disability and underwent plasma exchange. Methotrexate was substituted for the mycophenolate mofetil, which he was not tolerating.

The patient continued to experience severe neuropathy until given rituximab. Subsequent nerve conduction studies showed resolution of the neuropathic symptoms, with amelioration in velocity, amplitude, and latency, Dr. Roccatello said.

A second patient was a 61-year-old woman who had been treated for necrotizing glomerulonephritis with corticosteroids and cylophosphamide but was referred to Dr. Roccatello's center because of persistent fever, elevated cytoplasmic ANCA (c-ANCA) levels, weight loss, dyspnea, chest pain, and sinusitis characterized by complete blockage of the maxillary sinuses.

She also had multiple nodular lesions in the superior lobes of the lungs. Treatment with rituximab resulted in a 30% decrease in the number of pulmonary lesions by week 7, and in complete clearance by 9 months. Following treatment, this patient's urinary and inflammation markers and c-ANCA levels all normalized, he said.

Dr. Roccatello also has used rituximab in severe cryoglobulinemia, which is a systemic vasculitis usually associated with hepatitis C infection and sustained by the proliferation of oligoclonal B cells. A total of 12 patients with symptomatic type II mixed cryoglobulinemia were treated with six courses of rituximab in the same dose and schedule as the eight patients with ANCA-associated vasculitides, he said.

All 12 patients had polyneuropathy and renal involvement, with 6 having biopsy-proven diffuse membranoproliferative glomerulonephritis. Five patients had bone marrow clonal restriction, and three had large necrotizing skin ulcers.

Significant decreases were seen in levels of proteinuria, ESR, and RF during 18 months of follow-up, and bone marrow abnormalities were shown to have normalized in the three patients who underwent repeat biopsy. Skin ulcers and purpura, arthralgias, weakness, paresthesias, and fever improved or resolved in all patients, Dr. Roccatello reported.

Rituximab has been used in combination regimens, such as with corticosteroids and immunosuppressants for relapsing Wegener's granulomatosis. In another series presented at the congress, Dr. Achille Aouba reported on eight patients with Wegener's granulomatosis who experienced flares or failed to respond to multiple other immunomodulatory therapies, including anti-tumor necrosis factor-α blockers.

Disease manifestations included lung nodules in four patients, orbital pseudotumor in two, and gingival hyperplasia, mononeuritis multiplex, glomerulonephritis, rectal perforation, pyoderma gangrenosum, and myocardial involvement in one each.

While continuing on corticosteroids and immunosuppressants, seven of the patients received four weekly infusions of rituximab in doses of 375 mg/m

The median Birmingham vasculitis activity score (BVAS) before rituximab treatment was 14.3, with a range of 0–30.

At 4 months, five patients had BVAS scores of zero and three were in complete remission, said Dr. Aouba of the National Reference Center for Vasculitides, Hospital Cochin, Paris, and of the French Vasculitis Study Group.

An additional three were in partial remission, with BVAS scores of zero but persistent lung nodules, and two failed to respond.

Constitutional and vasculitis-related symptoms resolved more quickly than granulomatous manifestations, which regressed slowly over several months, Dr. Aouba said.

Rituximab was well tolerated, with the only adverse event being an urticarial rash in one patient, which developed after the third infusion.

In conclusion, the addition of rituximab to conventional treatment for relapsing Wegener's granulomatosis improved clinical outcome, Dr. Aouba said.

Necrotizing skin ulcers (above) developed in association with severe mixed cryoglobulinemia. Photos courtesy Dr. Dario Roccatello

SORRENTO, ITALY — Rituximab may provide a therapeutic option for patients with refractory, potentially life-threatening autoimmune vasculitic conditions that do not respond to conventional therapies or when dose-limiting toxicity occurs, Dr. Dario Roccatello said at the Fifth International Congress on Autoimmunity.

Although prognosis in the once rapidly fatal systemic vasculitides improved following the introduction of treatment with corticosteroids and cyclophosphamide, approximately one-fourth of patients cannot tolerate the associated side effects, and many relapse. Recent interest in the long-term management of these disorders therefore has centered on cyclophosphamide-sparing approaches, Dr. Roccatello said.

He reported on eight patients with systemic vasculitis who have been treated with this B cell-depleting agent. Their diagnoses included systemic micropolyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome. Six had kidney involvement, and necrotizing glomerulonephritis was present in four who underwent renal biopsy.

Intravenous rituximab was given in doses of 375 mg/m

Levels of the antineutrophil cytoplasmic antibodies (ANCA) that characterize these vasculitides decreased by fivefold following rituximab treatment, and one patient became ANCA-negative by week 4, said Dr. Roccatello of the University of Turin (Italy).

Treatment also resulted in significant decreases in pain and disease activity scores as measured on visual analog scales, with statistically significant decreases seen in levels of erythrocyte sedimentation rate (ESR), serum creatinine levels, proteinuria, and hematuria.

Weakness, paresthesias, arthralgias, and fever also resolved in the majority of patients.

One of the patients was a 38-year-old man who had involvement of the left carotid artery and elevations of ESR, C-reactive protein, and rheumatoid factor (RF). He was antibody positive for phospholipids and perinuclear ANCA (p-ANCA), and had symptoms including hematuria, fever, severe weakness, and paresthesia.

Initially he was treated with anticoagulants, gabapentin, and high-dose immunoglobulins, but after 2 months he had further elevations of p-ANCA and RF, as well as worsening neuropathy, and was treated with three steroid pulses and mycophenolate mofetil. One month later, he developed a leukocytic vasculitis with motor disability and underwent plasma exchange. Methotrexate was substituted for the mycophenolate mofetil, which he was not tolerating.

The patient continued to experience severe neuropathy until given rituximab. Subsequent nerve conduction studies showed resolution of the neuropathic symptoms, with amelioration in velocity, amplitude, and latency, Dr. Roccatello said.

A second patient was a 61-year-old woman who had been treated for necrotizing glomerulonephritis with corticosteroids and cylophosphamide but was referred to Dr. Roccatello's center because of persistent fever, elevated cytoplasmic ANCA (c-ANCA) levels, weight loss, dyspnea, chest pain, and sinusitis characterized by complete blockage of the maxillary sinuses.

She also had multiple nodular lesions in the superior lobes of the lungs. Treatment with rituximab resulted in a 30% decrease in the number of pulmonary lesions by week 7, and in complete clearance by 9 months. Following treatment, this patient's urinary and inflammation markers and c-ANCA levels all normalized, he said.

Dr. Roccatello also has used rituximab in severe cryoglobulinemia, which is a systemic vasculitis usually associated with hepatitis C infection and sustained by the proliferation of oligoclonal B cells. A total of 12 patients with symptomatic type II mixed cryoglobulinemia were treated with six courses of rituximab in the same dose and schedule as the eight patients with ANCA-associated vasculitides, he said.

All 12 patients had polyneuropathy and renal involvement, with 6 having biopsy-proven diffuse membranoproliferative glomerulonephritis. Five patients had bone marrow clonal restriction, and three had large necrotizing skin ulcers.

Significant decreases were seen in levels of proteinuria, ESR, and RF during 18 months of follow-up, and bone marrow abnormalities were shown to have normalized in the three patients who underwent repeat biopsy. Skin ulcers and purpura, arthralgias, weakness, paresthesias, and fever improved or resolved in all patients, Dr. Roccatello reported.

Rituximab has been used in combination regimens, such as with corticosteroids and immunosuppressants for relapsing Wegener's granulomatosis. In another series presented at the congress, Dr. Achille Aouba reported on eight patients with Wegener's granulomatosis who experienced flares or failed to respond to multiple other immunomodulatory therapies, including anti-tumor necrosis factor-α blockers.

Disease manifestations included lung nodules in four patients, orbital pseudotumor in two, and gingival hyperplasia, mononeuritis multiplex, glomerulonephritis, rectal perforation, pyoderma gangrenosum, and myocardial involvement in one each.

While continuing on corticosteroids and immunosuppressants, seven of the patients received four weekly infusions of rituximab in doses of 375 mg/m

The median Birmingham vasculitis activity score (BVAS) before rituximab treatment was 14.3, with a range of 0–30.

At 4 months, five patients had BVAS scores of zero and three were in complete remission, said Dr. Aouba of the National Reference Center for Vasculitides, Hospital Cochin, Paris, and of the French Vasculitis Study Group.

An additional three were in partial remission, with BVAS scores of zero but persistent lung nodules, and two failed to respond.

Constitutional and vasculitis-related symptoms resolved more quickly than granulomatous manifestations, which regressed slowly over several months, Dr. Aouba said.

Rituximab was well tolerated, with the only adverse event being an urticarial rash in one patient, which developed after the third infusion.

In conclusion, the addition of rituximab to conventional treatment for relapsing Wegener's granulomatosis improved clinical outcome, Dr. Aouba said.

Necrotizing skin ulcers (above) developed in association with severe mixed cryoglobulinemia. Photos courtesy Dr. Dario Roccatello

SORRENTO, ITALY — Patients with systemic lupus erythematosus are at high risk for the development of certain types of malignancy, particularly non-Hodgkin's lymphoma and cervical cancer, Dr. Emese Kiss said at the Fifth International Congress on Autoimmunity.

Improved treatments have resulted in greater life expectancy among patients with lupus, with the unintended consequence that morbidity and mortality from causes other than lupus itself have assumed increasing importance.

A retrospective analysis of data from 860 patients seen between 1970 and 2004 identified 37 cases of cancer, for an overall prevalence of 4.3%, reported Dr. Kiss of the University of Debrecen (Hungary).

When compared with age- and sex-matched controls, the resulting standardized incidence ratio for all cancers of 0.85 was not elevated, she said.

But the standardized incidence ratios for cervical cancer, hematologic malignancies, and non-Hodgkin's lymphoma were 1.74, 1.31, and 3.47, respectively.

The highest relative risks were 4.6 for non-Hodgkin's lymphoma and 2.3 for cervical cancer, she said.

During the study period 164 patients died, 18 of malignancies, for a cancer-related mortality of 11%.

In most other surveys of cancer among patients with lupus, elevated risks have been reported for lung, hepatobiliary, and hematologic malignancies. Some studies also have found increased frequency of breast, gynecologic, bladder, and prostate cancer, depending on age, race, and gender distribution.

Among the postulated reasons for the increased lymphoma risk in lupus patients are high inflammatory activity and uncontrolled B-cell proliferation, which increase the risk of oncogene translocations, Dr. Kiss explained in an interview.

Diffuse, large B-cell lymphomas that are derived primarily from peripheral activated B cells are the major types of lymphoma in patients with lupus as well as in those with rheumatoid arthritis. This can be considered indirect evidence supporting the role of inflammation and disease activity in the development of non-Hodgkin's lymphoma, she said.

The use of immune modulatory agents in treatment also may contribute, either by direct mutagenesis or by disturbing immune surveillance and thus allowing dysregulated proliferation of B cells, she said.

Another contributing factor may be the fact that lupus and non-Hodgkin's lymphoma share some clinical manifestations, including thrombocytopenia, leucopenia, anemia, lymphadenopathy, and hepatosplenomegaly. This may complicate and delay the diagnosis of non-Hodgkin's lymphoma.

The elevated risk for cervical cancer may relate to increased rates of infection with human papillomavirus or to impaired clearance of the virus. It also may be associated with the use of cytostatic drugs, although a direct association between human papillomavirus infection and treatment with cyclophosphamide or azathioprine could not be confirmed, Dr. Kiss said.

An important implication of these data is that increased attention must be paid to screening for these cancers, such as with Pap testing, she said.

An additional “surprising” finding in this analysis was that the malignant disorders appeared not as late complications, but most often within the first 5–10 years after the onset of lupus. “This suggests that immune suppressive therapy is not the only factor increasing cancer risk, and again supports the importance of high disease activity in the development of cancer,” she said.

The mean age at the onset of malignancy was 47 years. The earliest malignancies to develop were the hematologic and hepatobiliary cancers, while colorectal and gastric cancers appeared much later, sometimes more than 20 years after the diagnosis of systemic lupus erythematosus, Dr. Kiss said. Half of lupus patients do not survive long enough to develop gastrointestinal cancers, she said.

SORRENTO, ITALY — Patients with systemic lupus erythematosus are at high risk for the development of certain types of malignancy, particularly non-Hodgkin's lymphoma and cervical cancer, Dr. Emese Kiss said at the Fifth International Congress on Autoimmunity.

Improved treatments have resulted in greater life expectancy among patients with lupus, with the unintended consequence that morbidity and mortality from causes other than lupus itself have assumed increasing importance.

A retrospective analysis of data from 860 patients seen between 1970 and 2004 identified 37 cases of cancer, for an overall prevalence of 4.3%, reported Dr. Kiss of the University of Debrecen (Hungary).

When compared with age- and sex-matched controls, the resulting standardized incidence ratio for all cancers of 0.85 was not elevated, she said.

But the standardized incidence ratios for cervical cancer, hematologic malignancies, and non-Hodgkin's lymphoma were 1.74, 1.31, and 3.47, respectively.

The highest relative risks were 4.6 for non-Hodgkin's lymphoma and 2.3 for cervical cancer, she said.

During the study period 164 patients died, 18 of malignancies, for a cancer-related mortality of 11%.

In most other surveys of cancer among patients with lupus, elevated risks have been reported for lung, hepatobiliary, and hematologic malignancies. Some studies also have found increased frequency of breast, gynecologic, bladder, and prostate cancer, depending on age, race, and gender distribution.

Among the postulated reasons for the increased lymphoma risk in lupus patients are high inflammatory activity and uncontrolled B-cell proliferation, which increase the risk of oncogene translocations, Dr. Kiss explained in an interview.

Diffuse, large B-cell lymphomas that are derived primarily from peripheral activated B cells are the major types of lymphoma in patients with lupus as well as in those with rheumatoid arthritis. This can be considered indirect evidence supporting the role of inflammation and disease activity in the development of non-Hodgkin's lymphoma, she said.

The use of immune modulatory agents in treatment also may contribute, either by direct mutagenesis or by disturbing immune surveillance and thus allowing dysregulated proliferation of B cells, she said.

Another contributing factor may be the fact that lupus and non-Hodgkin's lymphoma share some clinical manifestations, including thrombocytopenia, leucopenia, anemia, lymphadenopathy, and hepatosplenomegaly. This may complicate and delay the diagnosis of non-Hodgkin's lymphoma.

The elevated risk for cervical cancer may relate to increased rates of infection with human papillomavirus or to impaired clearance of the virus. It also may be associated with the use of cytostatic drugs, although a direct association between human papillomavirus infection and treatment with cyclophosphamide or azathioprine could not be confirmed, Dr. Kiss said.

An important implication of these data is that increased attention must be paid to screening for these cancers, such as with Pap testing, she said.

An additional “surprising” finding in this analysis was that the malignant disorders appeared not as late complications, but most often within the first 5–10 years after the onset of lupus. “This suggests that immune suppressive therapy is not the only factor increasing cancer risk, and again supports the importance of high disease activity in the development of cancer,” she said.

The mean age at the onset of malignancy was 47 years. The earliest malignancies to develop were the hematologic and hepatobiliary cancers, while colorectal and gastric cancers appeared much later, sometimes more than 20 years after the diagnosis of systemic lupus erythematosus, Dr. Kiss said. Half of lupus patients do not survive long enough to develop gastrointestinal cancers, she said.

SORRENTO, ITALY — Patients with systemic lupus erythematosus are at high risk for the development of certain types of malignancy, particularly non-Hodgkin's lymphoma and cervical cancer, Dr. Emese Kiss said at the Fifth International Congress on Autoimmunity.

Improved treatments have resulted in greater life expectancy among patients with lupus, with the unintended consequence that morbidity and mortality from causes other than lupus itself have assumed increasing importance.

A retrospective analysis of data from 860 patients seen between 1970 and 2004 identified 37 cases of cancer, for an overall prevalence of 4.3%, reported Dr. Kiss of the University of Debrecen (Hungary).

When compared with age- and sex-matched controls, the resulting standardized incidence ratio for all cancers of 0.85 was not elevated, she said.

But the standardized incidence ratios for cervical cancer, hematologic malignancies, and non-Hodgkin's lymphoma were 1.74, 1.31, and 3.47, respectively.

The highest relative risks were 4.6 for non-Hodgkin's lymphoma and 2.3 for cervical cancer, she said.

During the study period 164 patients died, 18 of malignancies, for a cancer-related mortality of 11%.

In most other surveys of cancer among patients with lupus, elevated risks have been reported for lung, hepatobiliary, and hematologic malignancies. Some studies also have found increased frequency of breast, gynecologic, bladder, and prostate cancer, depending on age, race, and gender distribution.

Among the postulated reasons for the increased lymphoma risk in lupus patients are high inflammatory activity and uncontrolled B-cell proliferation, which increase the risk of oncogene translocations, Dr. Kiss explained in an interview.

Diffuse, large B-cell lymphomas that are derived primarily from peripheral activated B cells are the major types of lymphoma in patients with lupus as well as in those with rheumatoid arthritis. This can be considered indirect evidence supporting the role of inflammation and disease activity in the development of non-Hodgkin's lymphoma, she said.

The use of immune modulatory agents in treatment also may contribute, either by direct mutagenesis or by disturbing immune surveillance and thus allowing dysregulated proliferation of B cells, she said.

Another contributing factor may be the fact that lupus and non-Hodgkin's lymphoma share some clinical manifestations, including thrombocytopenia, leucopenia, anemia, lymphadenopathy, and hepatosplenomegaly. This may complicate and delay the diagnosis of non-Hodgkin's lymphoma.

The elevated risk for cervical cancer may relate to increased rates of infection with human papillomavirus or to impaired clearance of the virus. It also may be associated with the use of cytostatic drugs, although a direct association between human papillomavirus infection and treatment with cyclophosphamide or azathioprine could not be confirmed, Dr. Kiss said.

An important implication of these data is that increased attention must be paid to screening for these cancers, such as with Pap testing, she said.

An additional “surprising” finding in this analysis was that the malignant disorders appeared not as late complications, but most often within the first 5–10 years after the onset of lupus. “This suggests that immune suppressive therapy is not the only factor increasing cancer risk, and again supports the importance of high disease activity in the development of cancer,” she said.

The mean age at the onset of malignancy was 47 years. The earliest malignancies to develop were the hematologic and hepatobiliary cancers, while colorectal and gastric cancers appeared much later, sometimes more than 20 years after the diagnosis of systemic lupus erythematosus, Dr. Kiss said. Half of lupus patients do not survive long enough to develop gastrointestinal cancers, she said.

SORRENTO, ITALY — Patients with pemphigus who are younger than 40 years at the time of diagnosis and whose first remission is brief are likely to have a more severe course of disease and multiple relapses, Dr. David Mimouni said at the Fifth International Congress on Autoimmunity.

Much remains unknown about the natural history of pemphigus. In an attempt to address this, a survey was undertaken of 155 patients diagnosed with some form of pemphigus and treated at an Israeli center between 1976 and 2004.

Follow-up for the patients ranged from 4 to 28 years. Of these patients, 94 were female. The age distribution at disease onset was typical of pemphigus, peaking between 40 and 50 years, said Dr. Mimouni of the department of dermatology, Rabin Medical Center, Petah Tiqwa, Israel.

Pemphigus vulgaris was the diagnosis in 144 patients. The remainder had diagnoses of pemphigus foliaceus, in which only the skin is involved and the mucous membranes are spared; pemphigus erythematosus, with features of both pemphigus and lupus; and paraneoplastic pemphigus.

In only 16 patients could a precipitating factor such as stress, drugs, or sun exposure be identified, he said.

The initial site of involvement was the mucosa alone in 50%, the skin alone in 47%, and both in 3%. At the time of follow-up, however, involvement limited to the mucosa or skin was seen only in 21% and 24%, respectively, while both sites were affected in 55%, Dr. Mimouni said.

A total of 91 patients were of Ashkenazi Jewish origin, while 58 were of Sephardic origin, and 6 were Arab. At the time of follow-up, the Sephardic patients were significantly less likely to be in remission than were the Ashkenazi, which was surprising, because a strong genetic link had previously been established for Ashkenazi origin, Dr. Mimouni said.

Younger patients and those whose initial remission lasted less than a year also were less likely to be in remission at the time of follow-up, as were those with mucosal involvement.

All patients had been treated with high doses of steroids, usually between 1.5 and 2 mg/kg per day, for periods up to 10 years. Most also had adjuvant therapy, most commonly with azathioprine, although recently other agents such as mycophenolate mofetil had been used.

Only 2% of the study patients had never had a relapse following treatment, while 40% had one to two relapses, and 58% had more than three, he said.

A total of 16 patients died. The causes of death were cancer, ischemic heart disease, and pulmonary embolism. None of the deaths was directly related to pemphigus, which represents a marked change from 1950, when 90% of patients would have died of pemphigus within 2 years, Dr. Mimouni said.

This study suggests that although there still is no cure for pemphigus, the morbidity and mortality associated with the disease have decreased significantly.

Progress has also been made in deciphering some of the underlying autoimmune processes in these conditions. For example, it is now known that pemphigus vulgaris is characterized by the presence of antibodies to desmoglein 1 and 3, which are adhesion molecules located between epidermal cells. Targeting these desmosomal antigens results in the loss of adhesion between keratinocytes, causing erosions and blisters, Dr. Mimouni explained.

SORRENTO, ITALY — Patients with pemphigus who are younger than 40 years at the time of diagnosis and whose first remission is brief are likely to have a more severe course of disease and multiple relapses, Dr. David Mimouni said at the Fifth International Congress on Autoimmunity.

Much remains unknown about the natural history of pemphigus. In an attempt to address this, a survey was undertaken of 155 patients diagnosed with some form of pemphigus and treated at an Israeli center between 1976 and 2004.

Follow-up for the patients ranged from 4 to 28 years. Of these patients, 94 were female. The age distribution at disease onset was typical of pemphigus, peaking between 40 and 50 years, said Dr. Mimouni of the department of dermatology, Rabin Medical Center, Petah Tiqwa, Israel.

Pemphigus vulgaris was the diagnosis in 144 patients. The remainder had diagnoses of pemphigus foliaceus, in which only the skin is involved and the mucous membranes are spared; pemphigus erythematosus, with features of both pemphigus and lupus; and paraneoplastic pemphigus.

In only 16 patients could a precipitating factor such as stress, drugs, or sun exposure be identified, he said.

The initial site of involvement was the mucosa alone in 50%, the skin alone in 47%, and both in 3%. At the time of follow-up, however, involvement limited to the mucosa or skin was seen only in 21% and 24%, respectively, while both sites were affected in 55%, Dr. Mimouni said.

A total of 91 patients were of Ashkenazi Jewish origin, while 58 were of Sephardic origin, and 6 were Arab. At the time of follow-up, the Sephardic patients were significantly less likely to be in remission than were the Ashkenazi, which was surprising, because a strong genetic link had previously been established for Ashkenazi origin, Dr. Mimouni said.

Younger patients and those whose initial remission lasted less than a year also were less likely to be in remission at the time of follow-up, as were those with mucosal involvement.

All patients had been treated with high doses of steroids, usually between 1.5 and 2 mg/kg per day, for periods up to 10 years. Most also had adjuvant therapy, most commonly with azathioprine, although recently other agents such as mycophenolate mofetil had been used.

Only 2% of the study patients had never had a relapse following treatment, while 40% had one to two relapses, and 58% had more than three, he said.

A total of 16 patients died. The causes of death were cancer, ischemic heart disease, and pulmonary embolism. None of the deaths was directly related to pemphigus, which represents a marked change from 1950, when 90% of patients would have died of pemphigus within 2 years, Dr. Mimouni said.

This study suggests that although there still is no cure for pemphigus, the morbidity and mortality associated with the disease have decreased significantly.

Progress has also been made in deciphering some of the underlying autoimmune processes in these conditions. For example, it is now known that pemphigus vulgaris is characterized by the presence of antibodies to desmoglein 1 and 3, which are adhesion molecules located between epidermal cells. Targeting these desmosomal antigens results in the loss of adhesion between keratinocytes, causing erosions and blisters, Dr. Mimouni explained.

SORRENTO, ITALY — Patients with pemphigus who are younger than 40 years at the time of diagnosis and whose first remission is brief are likely to have a more severe course of disease and multiple relapses, Dr. David Mimouni said at the Fifth International Congress on Autoimmunity.

Much remains unknown about the natural history of pemphigus. In an attempt to address this, a survey was undertaken of 155 patients diagnosed with some form of pemphigus and treated at an Israeli center between 1976 and 2004.

Follow-up for the patients ranged from 4 to 28 years. Of these patients, 94 were female. The age distribution at disease onset was typical of pemphigus, peaking between 40 and 50 years, said Dr. Mimouni of the department of dermatology, Rabin Medical Center, Petah Tiqwa, Israel.

Pemphigus vulgaris was the diagnosis in 144 patients. The remainder had diagnoses of pemphigus foliaceus, in which only the skin is involved and the mucous membranes are spared; pemphigus erythematosus, with features of both pemphigus and lupus; and paraneoplastic pemphigus.

In only 16 patients could a precipitating factor such as stress, drugs, or sun exposure be identified, he said.

The initial site of involvement was the mucosa alone in 50%, the skin alone in 47%, and both in 3%. At the time of follow-up, however, involvement limited to the mucosa or skin was seen only in 21% and 24%, respectively, while both sites were affected in 55%, Dr. Mimouni said.

A total of 91 patients were of Ashkenazi Jewish origin, while 58 were of Sephardic origin, and 6 were Arab. At the time of follow-up, the Sephardic patients were significantly less likely to be in remission than were the Ashkenazi, which was surprising, because a strong genetic link had previously been established for Ashkenazi origin, Dr. Mimouni said.

Younger patients and those whose initial remission lasted less than a year also were less likely to be in remission at the time of follow-up, as were those with mucosal involvement.

All patients had been treated with high doses of steroids, usually between 1.5 and 2 mg/kg per day, for periods up to 10 years. Most also had adjuvant therapy, most commonly with azathioprine, although recently other agents such as mycophenolate mofetil had been used.

Only 2% of the study patients had never had a relapse following treatment, while 40% had one to two relapses, and 58% had more than three, he said.

A total of 16 patients died. The causes of death were cancer, ischemic heart disease, and pulmonary embolism. None of the deaths was directly related to pemphigus, which represents a marked change from 1950, when 90% of patients would have died of pemphigus within 2 years, Dr. Mimouni said.

This study suggests that although there still is no cure for pemphigus, the morbidity and mortality associated with the disease have decreased significantly.

Progress has also been made in deciphering some of the underlying autoimmune processes in these conditions. For example, it is now known that pemphigus vulgaris is characterized by the presence of antibodies to desmoglein 1 and 3, which are adhesion molecules located between epidermal cells. Targeting these desmosomal antigens results in the loss of adhesion between keratinocytes, causing erosions and blisters, Dr. Mimouni explained.

SORRENTO, ITALY — The posterior uveitis known as birdshot chorioretinopathy appears to be an eye-restricted disease, reported Dr. Christian Pagnoux at the Fifth International Congress on Autoimmunity.

In a careful assessment of the largest series to date of patients with birdshot chorioretinopathy—so named because of the distinct shotgun-like scatter pattern of hypopigmented spots on the fundus—some were found to exhibit “intriguing” extraocular features, but there was no convincing evidence of systemic involvement, said Dr. Pagnoux of Cochin Hospital, Paris.

Previous studies of birdshot chorioretinopathy, in which patients complain of floaters, blurred vision, nyctalopia, and photophobia, have not addressed the possibility of patients having extraocular manifestations despite the likelihood that the disorder is autoimmune in nature.

The evidence suggesting that birdshot chorioretinopathy is an autoimmune disorder includes a strong association with the human leukocyte antigen (HLA)-A*29 gene. Moreover, clinical features of the disease resemble autoimmune S-antigen-induced uveoretinitis, and some patients have granulomatous histology findings and features associated with vasculitis, according to Dr. Pagnoux. “However, if it indeed is an autoimmune disease, it would be one of the rare—and possibly the only—autoimmune disease that is restricted to one organ,” he said in an interview.

A longitudinal cohort study initiated by ophthalmologists at Cochin Hospital, which is the French National Reference Center for Vasculitides, provided the opportunity for Dr. Pagnoux and his colleagues from the French Vasculitis Study Group to investigate disease manifestations in 118 patients.

Mean age was 51 years, and there was a slight male predominance. Each patient underwent a 30-minute medical interview using a standardized report form, and data on medical history before and after the onset of birdshot chorioretinopathy were collected.

Among the study findings were that 16% had drug allergies, 9% had asthma, 8% had diabetes, and 10% had thyroid disease. One patient had antiphospholipid syndrome, three had Raynaud's phenomenon, and five reported a history of psoriasis. In addition, 27% were hypertensive, and 14% had sinusitis. Hearing loss was reported by 7%. At the time of disease onset, 19% of patients also reported arthralgias, but none had arthritis or synovitis, Dr. Pagnoux said.

The incidence of these maladies is quite similar to those reported by the French general population, he said. “We also did not find any manifestations suggesting inflammation outside the eyes, such as elevated C-reactive protein levels. “I think one could say today, with a certain degree of confidence, that birdshot chorioretinopathy is indeed an eye-restricted disease,” he said.

Nonetheless, certain findings such as hearing loss, hypertension, and psoriasis are of interest and merit further attention as potential extraocular disease manifestations. Study limitations include the non-population control design and the potential for recall bias. However, the use of standardized report forms by physicians specializing in vasculitis may counterbalance these potential drawbacks, he said.

The study is ongoing, and patients will be re-evaluated every 5 years with the goal of providing a clearer picture of the natural history of the disease, particularly when macular edema occurs and visual acuity is lost.

Multiple distinctive hypopigmented lesions shown clustered around the optic disk: Retinal depigmentation reveals veins on transparency, and slight edema is visible. Courtesy Dr. Pr Brézin/Cochin Hospital/Paris

SORRENTO, ITALY — The posterior uveitis known as birdshot chorioretinopathy appears to be an eye-restricted disease, reported Dr. Christian Pagnoux at the Fifth International Congress on Autoimmunity.

In a careful assessment of the largest series to date of patients with birdshot chorioretinopathy—so named because of the distinct shotgun-like scatter pattern of hypopigmented spots on the fundus—some were found to exhibit “intriguing” extraocular features, but there was no convincing evidence of systemic involvement, said Dr. Pagnoux of Cochin Hospital, Paris.

Previous studies of birdshot chorioretinopathy, in which patients complain of floaters, blurred vision, nyctalopia, and photophobia, have not addressed the possibility of patients having extraocular manifestations despite the likelihood that the disorder is autoimmune in nature.

The evidence suggesting that birdshot chorioretinopathy is an autoimmune disorder includes a strong association with the human leukocyte antigen (HLA)-A*29 gene. Moreover, clinical features of the disease resemble autoimmune S-antigen-induced uveoretinitis, and some patients have granulomatous histology findings and features associated with vasculitis, according to Dr. Pagnoux. “However, if it indeed is an autoimmune disease, it would be one of the rare—and possibly the only—autoimmune disease that is restricted to one organ,” he said in an interview.

A longitudinal cohort study initiated by ophthalmologists at Cochin Hospital, which is the French National Reference Center for Vasculitides, provided the opportunity for Dr. Pagnoux and his colleagues from the French Vasculitis Study Group to investigate disease manifestations in 118 patients.

Mean age was 51 years, and there was a slight male predominance. Each patient underwent a 30-minute medical interview using a standardized report form, and data on medical history before and after the onset of birdshot chorioretinopathy were collected.

Among the study findings were that 16% had drug allergies, 9% had asthma, 8% had diabetes, and 10% had thyroid disease. One patient had antiphospholipid syndrome, three had Raynaud's phenomenon, and five reported a history of psoriasis. In addition, 27% were hypertensive, and 14% had sinusitis. Hearing loss was reported by 7%. At the time of disease onset, 19% of patients also reported arthralgias, but none had arthritis or synovitis, Dr. Pagnoux said.

The incidence of these maladies is quite similar to those reported by the French general population, he said. “We also did not find any manifestations suggesting inflammation outside the eyes, such as elevated C-reactive protein levels. “I think one could say today, with a certain degree of confidence, that birdshot chorioretinopathy is indeed an eye-restricted disease,” he said.

Nonetheless, certain findings such as hearing loss, hypertension, and psoriasis are of interest and merit further attention as potential extraocular disease manifestations. Study limitations include the non-population control design and the potential for recall bias. However, the use of standardized report forms by physicians specializing in vasculitis may counterbalance these potential drawbacks, he said.

The study is ongoing, and patients will be re-evaluated every 5 years with the goal of providing a clearer picture of the natural history of the disease, particularly when macular edema occurs and visual acuity is lost.

Multiple distinctive hypopigmented lesions shown clustered around the optic disk: Retinal depigmentation reveals veins on transparency, and slight edema is visible. Courtesy Dr. Pr Brézin/Cochin Hospital/Paris

SORRENTO, ITALY — The posterior uveitis known as birdshot chorioretinopathy appears to be an eye-restricted disease, reported Dr. Christian Pagnoux at the Fifth International Congress on Autoimmunity.

In a careful assessment of the largest series to date of patients with birdshot chorioretinopathy—so named because of the distinct shotgun-like scatter pattern of hypopigmented spots on the fundus—some were found to exhibit “intriguing” extraocular features, but there was no convincing evidence of systemic involvement, said Dr. Pagnoux of Cochin Hospital, Paris.

Previous studies of birdshot chorioretinopathy, in which patients complain of floaters, blurred vision, nyctalopia, and photophobia, have not addressed the possibility of patients having extraocular manifestations despite the likelihood that the disorder is autoimmune in nature.

The evidence suggesting that birdshot chorioretinopathy is an autoimmune disorder includes a strong association with the human leukocyte antigen (HLA)-A*29 gene. Moreover, clinical features of the disease resemble autoimmune S-antigen-induced uveoretinitis, and some patients have granulomatous histology findings and features associated with vasculitis, according to Dr. Pagnoux. “However, if it indeed is an autoimmune disease, it would be one of the rare—and possibly the only—autoimmune disease that is restricted to one organ,” he said in an interview.

A longitudinal cohort study initiated by ophthalmologists at Cochin Hospital, which is the French National Reference Center for Vasculitides, provided the opportunity for Dr. Pagnoux and his colleagues from the French Vasculitis Study Group to investigate disease manifestations in 118 patients.

Mean age was 51 years, and there was a slight male predominance. Each patient underwent a 30-minute medical interview using a standardized report form, and data on medical history before and after the onset of birdshot chorioretinopathy were collected.

Among the study findings were that 16% had drug allergies, 9% had asthma, 8% had diabetes, and 10% had thyroid disease. One patient had antiphospholipid syndrome, three had Raynaud's phenomenon, and five reported a history of psoriasis. In addition, 27% were hypertensive, and 14% had sinusitis. Hearing loss was reported by 7%. At the time of disease onset, 19% of patients also reported arthralgias, but none had arthritis or synovitis, Dr. Pagnoux said.

The incidence of these maladies is quite similar to those reported by the French general population, he said. “We also did not find any manifestations suggesting inflammation outside the eyes, such as elevated C-reactive protein levels. “I think one could say today, with a certain degree of confidence, that birdshot chorioretinopathy is indeed an eye-restricted disease,” he said.

Nonetheless, certain findings such as hearing loss, hypertension, and psoriasis are of interest and merit further attention as potential extraocular disease manifestations. Study limitations include the non-population control design and the potential for recall bias. However, the use of standardized report forms by physicians specializing in vasculitis may counterbalance these potential drawbacks, he said.

The study is ongoing, and patients will be re-evaluated every 5 years with the goal of providing a clearer picture of the natural history of the disease, particularly when macular edema occurs and visual acuity is lost.

Multiple distinctive hypopigmented lesions shown clustered around the optic disk: Retinal depigmentation reveals veins on transparency, and slight edema is visible. Courtesy Dr. Pr Brézin/Cochin Hospital/Paris

Treatment with adalimumab significantly improved quality of life and functioning among patients with moderate to severe psoriatic arthritis at 24 weeks, reported Dr. Dafna D. Gladman.

Previous analyses from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), which is the largest randomized controlled trial of a tumor necrosis factor (TNF)-α inhibitor in psoriatic arthritis, have demonstrated that treatment with this drug significantly improves joint and skin manifestations and reduces radiographic disease progression.

But because psoriatic arthritis primarily afflicts patients in the productive years, 30–55 years, restoring function and reducing work-related disability also could help ease the economic burden of this disease, according to Dr. Gladman of the University of Toronto Rheumatic Disease Unit.

Among the 313 patients in ADEPT, those receiving adalimumab had a mean decrease of 0.4 points from a baseline score of 1.0 on the disease-specific Health Assessment Questionnaire Disability Index, which has a range of 0 to 3, while those receiving placebo had a decrease of 0.1 points, Dr. Gladman and colleagues reported (Ann. Rheum. Dis. [Epub doi: 10.1136/ard.2006.057901

By week 12, 33.8% of patients in the active treatment group had complete resolution of functional loss, compared with 14.3% of those in the placebo group, with similar results being seen at week 24, according to the investigators. Statistically significant and clinically important improvements also were seen at week 24 in seven of the eight domains of the Short Form 36 Health Survey among the adalimumab-treated patients, whereas patients receiving placebo did not experience clinically important improvements in any domain.

The investigators acknowledged that a limitation of their study was its short duration, but noted that data from the long-term, open-label extension of ADEPT are being assessed.

Treatment with adalimumab significantly improved quality of life and functioning among patients with moderate to severe psoriatic arthritis at 24 weeks, reported Dr. Dafna D. Gladman.

Previous analyses from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), which is the largest randomized controlled trial of a tumor necrosis factor (TNF)-α inhibitor in psoriatic arthritis, have demonstrated that treatment with this drug significantly improves joint and skin manifestations and reduces radiographic disease progression.

But because psoriatic arthritis primarily afflicts patients in the productive years, 30–55 years, restoring function and reducing work-related disability also could help ease the economic burden of this disease, according to Dr. Gladman of the University of Toronto Rheumatic Disease Unit.

Among the 313 patients in ADEPT, those receiving adalimumab had a mean decrease of 0.4 points from a baseline score of 1.0 on the disease-specific Health Assessment Questionnaire Disability Index, which has a range of 0 to 3, while those receiving placebo had a decrease of 0.1 points, Dr. Gladman and colleagues reported (Ann. Rheum. Dis. [Epub doi: 10.1136/ard.2006.057901

By week 12, 33.8% of patients in the active treatment group had complete resolution of functional loss, compared with 14.3% of those in the placebo group, with similar results being seen at week 24, according to the investigators. Statistically significant and clinically important improvements also were seen at week 24 in seven of the eight domains of the Short Form 36 Health Survey among the adalimumab-treated patients, whereas patients receiving placebo did not experience clinically important improvements in any domain.

The investigators acknowledged that a limitation of their study was its short duration, but noted that data from the long-term, open-label extension of ADEPT are being assessed.

Treatment with adalimumab significantly improved quality of life and functioning among patients with moderate to severe psoriatic arthritis at 24 weeks, reported Dr. Dafna D. Gladman.

Previous analyses from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), which is the largest randomized controlled trial of a tumor necrosis factor (TNF)-α inhibitor in psoriatic arthritis, have demonstrated that treatment with this drug significantly improves joint and skin manifestations and reduces radiographic disease progression.

But because psoriatic arthritis primarily afflicts patients in the productive years, 30–55 years, restoring function and reducing work-related disability also could help ease the economic burden of this disease, according to Dr. Gladman of the University of Toronto Rheumatic Disease Unit.

Among the 313 patients in ADEPT, those receiving adalimumab had a mean decrease of 0.4 points from a baseline score of 1.0 on the disease-specific Health Assessment Questionnaire Disability Index, which has a range of 0 to 3, while those receiving placebo had a decrease of 0.1 points, Dr. Gladman and colleagues reported (Ann. Rheum. Dis. [Epub doi: 10.1136/ard.2006.057901

By week 12, 33.8% of patients in the active treatment group had complete resolution of functional loss, compared with 14.3% of those in the placebo group, with similar results being seen at week 24, according to the investigators. Statistically significant and clinically important improvements also were seen at week 24 in seven of the eight domains of the Short Form 36 Health Survey among the adalimumab-treated patients, whereas patients receiving placebo did not experience clinically important improvements in any domain.

The investigators acknowledged that a limitation of their study was its short duration, but noted that data from the long-term, open-label extension of ADEPT are being assessed.

WASHINGTON —The use of anti-tumor necrosis factor-α (TNF-α) agents in patients with rheumatoid arthritis is associated with an increased risk for the development of palmoplantar psoriasis, Dr. Jacob A. Aelion reported at the annual meeting of the American College of Rheumatology.

There have been sporadic reports in the literature of psoriasiform skin lesions occurring after the initiation of anti-TNF-α therapy, but it has not been determined whether it is the therapy itself that increases the risk.

In a cohort of 1,195 patients with rheumatoid arthritis who were receiving methotrexate plus etanercept, adalimumab, or infliximab and 788 patients who were receiving methotrexate monotherapy between 1999 and 2005, seven cases of psoriasis developed, all in the group of patients receiving the anti-TNF-α agents, Dr. Aelion reported in a poster session.

None of these patients who developed psoriasis had a family history of the condition, and skin involvement was limited to the palms and/or soles in all seven patients.

The affected patients all were female. Two were receiving infliximab, two were receiving etanercept, and three were being treated with adalimumab.

Withdrawal of the anti-TNF-α therapy resulted in regression or resolution in three, and in two of these, relapse occurred when infliximab was restarted, wrote Dr. Aelion of the Arthritis Clinic, Jackson, Tenn.

The development of psoriasis was not limited to a single anti-TNF-α agent, but rather seemed to be a class effect of TNF blockade itself.

“This finding is surprising since TNF-α inhibitors have been used successfully in the treatment of psoriasis and psoriatic arthritis,” he wrote.

The pathogenic means by which this distinct adverse effect of TNF-α inhibition occurs in rheumatoid arthritis patients remain obscure.

“A possible explanation resides in the dual immunologic role of TNF-α. Besides its role as a proinflammatory cytokine, TNF-α is also known to exert an immunosuppressive effect by regulating antigen-presenting cell functions and apoptosis of potentially autoreactive T cells,” he continued.

Thus, blocking TNF-α may result in the unmasking of other autoimmune disorders in susceptible patients.

Nonetheless, these findings should not discourage the use of this class of drugs in patients with rheumatoid arthritis, in whom the overall benefits greatly outweigh the risks of the development of skin disorders, Dr. Aelion concluded at the meeting.

WASHINGTON —The use of anti-tumor necrosis factor-α (TNF-α) agents in patients with rheumatoid arthritis is associated with an increased risk for the development of palmoplantar psoriasis, Dr. Jacob A. Aelion reported at the annual meeting of the American College of Rheumatology.

There have been sporadic reports in the literature of psoriasiform skin lesions occurring after the initiation of anti-TNF-α therapy, but it has not been determined whether it is the therapy itself that increases the risk.

In a cohort of 1,195 patients with rheumatoid arthritis who were receiving methotrexate plus etanercept, adalimumab, or infliximab and 788 patients who were receiving methotrexate monotherapy between 1999 and 2005, seven cases of psoriasis developed, all in the group of patients receiving the anti-TNF-α agents, Dr. Aelion reported in a poster session.

None of these patients who developed psoriasis had a family history of the condition, and skin involvement was limited to the palms and/or soles in all seven patients.

The affected patients all were female. Two were receiving infliximab, two were receiving etanercept, and three were being treated with adalimumab.

Withdrawal of the anti-TNF-α therapy resulted in regression or resolution in three, and in two of these, relapse occurred when infliximab was restarted, wrote Dr. Aelion of the Arthritis Clinic, Jackson, Tenn.

The development of psoriasis was not limited to a single anti-TNF-α agent, but rather seemed to be a class effect of TNF blockade itself.

“This finding is surprising since TNF-α inhibitors have been used successfully in the treatment of psoriasis and psoriatic arthritis,” he wrote.

The pathogenic means by which this distinct adverse effect of TNF-α inhibition occurs in rheumatoid arthritis patients remain obscure.

“A possible explanation resides in the dual immunologic role of TNF-α. Besides its role as a proinflammatory cytokine, TNF-α is also known to exert an immunosuppressive effect by regulating antigen-presenting cell functions and apoptosis of potentially autoreactive T cells,” he continued.

Thus, blocking TNF-α may result in the unmasking of other autoimmune disorders in susceptible patients.

Nonetheless, these findings should not discourage the use of this class of drugs in patients with rheumatoid arthritis, in whom the overall benefits greatly outweigh the risks of the development of skin disorders, Dr. Aelion concluded at the meeting.

WASHINGTON —The use of anti-tumor necrosis factor-α (TNF-α) agents in patients with rheumatoid arthritis is associated with an increased risk for the development of palmoplantar psoriasis, Dr. Jacob A. Aelion reported at the annual meeting of the American College of Rheumatology.

There have been sporadic reports in the literature of psoriasiform skin lesions occurring after the initiation of anti-TNF-α therapy, but it has not been determined whether it is the therapy itself that increases the risk.

In a cohort of 1,195 patients with rheumatoid arthritis who were receiving methotrexate plus etanercept, adalimumab, or infliximab and 788 patients who were receiving methotrexate monotherapy between 1999 and 2005, seven cases of psoriasis developed, all in the group of patients receiving the anti-TNF-α agents, Dr. Aelion reported in a poster session.

None of these patients who developed psoriasis had a family history of the condition, and skin involvement was limited to the palms and/or soles in all seven patients.

The affected patients all were female. Two were receiving infliximab, two were receiving etanercept, and three were being treated with adalimumab.

Withdrawal of the anti-TNF-α therapy resulted in regression or resolution in three, and in two of these, relapse occurred when infliximab was restarted, wrote Dr. Aelion of the Arthritis Clinic, Jackson, Tenn.

The development of psoriasis was not limited to a single anti-TNF-α agent, but rather seemed to be a class effect of TNF blockade itself.

“This finding is surprising since TNF-α inhibitors have been used successfully in the treatment of psoriasis and psoriatic arthritis,” he wrote.

The pathogenic means by which this distinct adverse effect of TNF-α inhibition occurs in rheumatoid arthritis patients remain obscure.

“A possible explanation resides in the dual immunologic role of TNF-α. Besides its role as a proinflammatory cytokine, TNF-α is also known to exert an immunosuppressive effect by regulating antigen-presenting cell functions and apoptosis of potentially autoreactive T cells,” he continued.

Thus, blocking TNF-α may result in the unmasking of other autoimmune disorders in susceptible patients.

Nonetheless, these findings should not discourage the use of this class of drugs in patients with rheumatoid arthritis, in whom the overall benefits greatly outweigh the risks of the development of skin disorders, Dr. Aelion concluded at the meeting.

NOORDWIJK, NETHERLANDS — Vitamin D supplementation was protective against late relapse of melanoma, particularly among patients who carry certain polymorphisms of the vitamin D receptor, Dr. Julia Newton Bishop reported at a conference on melanoma sponsored by Imedex Inc.

“In recent years there has been considerable interest in vitamin D because of its diverse functions, including antiproliferative and antiangiogenic effects,” Dr. Newton Bishop said.

The observation of the vitamin's effect on melanoma relapse emerged from a case-control study that included 143 patients who relapsed more than 3 years after surgical removal of their primary tumor, and 189 patients matched for age, sex, and Breslow thickness who did not relapse.

“Our hypothesis was that relapses and deaths within the first 3 years are likely to be related to the genetic and epigenetic effects of the tumor,” she said. Later relapses, in contrast, may relate to environmental effects on persisting melanoma cells.

Study participants filled out a questionnaire on dietary habits, vitamin supplementation, and sun exposure history. Serum and DNA were obtained to test for two known functional vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs), Cdx-2 and FOKl, and three noncoding SNPs, Apal, Bsml, and Taql, that have been shown to be associated with altered levels of VDR expression.

Data analysis revealed that there were no differences between cases and controls with regard to overall dietary practices or Fitzpatrick skin types.

Nor were there differences in time spent sunbathing or in the number of reported sunburn episodes either before or after diagnosis.

Although more relapsing patients reported using sunblock after the removal of their tumor than controls—91% vs. 85%—this difference was not statistically significant, said Dr. Newton Bishop of the Genetic Epidemiology Division, Cancer Research U.K., St. James's University Hospital, Leeds, England.

However, there were significant differences in vitamin D supplement use during the year prior to relapse, with 42% of controls and 28% of relapsing patients reporting that they took supplementary vitamin D. The odds ratio was 0.54 for relapse among those with a history of vitamin D supplement use, she said.

Serum vitamin D levels were significantly higher in those taking the supplement than in those who did not: a mean level of 54.3 nmol/L compared with 42.8 nmol/L. These measures confirmed patients' reports of taking the vitamin, she said.

VDR genotype results were available for 300 of the participants. None of the SNPs showed a significant association with relapse overall, but among patients who carried one or more copies of the variant Cdx-2 allele for increased VDR activity and expression, supplement use was associated with a highly significant reduced risk of relapse, with an odds ratio of 0.1.

Among patients who were homozygous for the wild-type variant of Taql associated with increased expression of VDR, there also was a significant reduction in risk of relapse, again with an odds ratio of 0.1.

“The observed protective effects of vitamin D intake and interaction with VDR genotype suggest that [this vitamin] is an important therapeutic candidate, which must be urgently evaluated further,” she said.

NOORDWIJK, NETHERLANDS — Vitamin D supplementation was protective against late relapse of melanoma, particularly among patients who carry certain polymorphisms of the vitamin D receptor, Dr. Julia Newton Bishop reported at a conference on melanoma sponsored by Imedex Inc.

“In recent years there has been considerable interest in vitamin D because of its diverse functions, including antiproliferative and antiangiogenic effects,” Dr. Newton Bishop said.

The observation of the vitamin's effect on melanoma relapse emerged from a case-control study that included 143 patients who relapsed more than 3 years after surgical removal of their primary tumor, and 189 patients matched for age, sex, and Breslow thickness who did not relapse.

“Our hypothesis was that relapses and deaths within the first 3 years are likely to be related to the genetic and epigenetic effects of the tumor,” she said. Later relapses, in contrast, may relate to environmental effects on persisting melanoma cells.

Study participants filled out a questionnaire on dietary habits, vitamin supplementation, and sun exposure history. Serum and DNA were obtained to test for two known functional vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs), Cdx-2 and FOKl, and three noncoding SNPs, Apal, Bsml, and Taql, that have been shown to be associated with altered levels of VDR expression.

Data analysis revealed that there were no differences between cases and controls with regard to overall dietary practices or Fitzpatrick skin types.

Nor were there differences in time spent sunbathing or in the number of reported sunburn episodes either before or after diagnosis.

Although more relapsing patients reported using sunblock after the removal of their tumor than controls—91% vs. 85%—this difference was not statistically significant, said Dr. Newton Bishop of the Genetic Epidemiology Division, Cancer Research U.K., St. James's University Hospital, Leeds, England.

However, there were significant differences in vitamin D supplement use during the year prior to relapse, with 42% of controls and 28% of relapsing patients reporting that they took supplementary vitamin D. The odds ratio was 0.54 for relapse among those with a history of vitamin D supplement use, she said.

Serum vitamin D levels were significantly higher in those taking the supplement than in those who did not: a mean level of 54.3 nmol/L compared with 42.8 nmol/L. These measures confirmed patients' reports of taking the vitamin, she said.

VDR genotype results were available for 300 of the participants. None of the SNPs showed a significant association with relapse overall, but among patients who carried one or more copies of the variant Cdx-2 allele for increased VDR activity and expression, supplement use was associated with a highly significant reduced risk of relapse, with an odds ratio of 0.1.

Among patients who were homozygous for the wild-type variant of Taql associated with increased expression of VDR, there also was a significant reduction in risk of relapse, again with an odds ratio of 0.1.

“The observed protective effects of vitamin D intake and interaction with VDR genotype suggest that [this vitamin] is an important therapeutic candidate, which must be urgently evaluated further,” she said.

NOORDWIJK, NETHERLANDS — Vitamin D supplementation was protective against late relapse of melanoma, particularly among patients who carry certain polymorphisms of the vitamin D receptor, Dr. Julia Newton Bishop reported at a conference on melanoma sponsored by Imedex Inc.

“In recent years there has been considerable interest in vitamin D because of its diverse functions, including antiproliferative and antiangiogenic effects,” Dr. Newton Bishop said.

The observation of the vitamin's effect on melanoma relapse emerged from a case-control study that included 143 patients who relapsed more than 3 years after surgical removal of their primary tumor, and 189 patients matched for age, sex, and Breslow thickness who did not relapse.

“Our hypothesis was that relapses and deaths within the first 3 years are likely to be related to the genetic and epigenetic effects of the tumor,” she said. Later relapses, in contrast, may relate to environmental effects on persisting melanoma cells.

Study participants filled out a questionnaire on dietary habits, vitamin supplementation, and sun exposure history. Serum and DNA were obtained to test for two known functional vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs), Cdx-2 and FOKl, and three noncoding SNPs, Apal, Bsml, and Taql, that have been shown to be associated with altered levels of VDR expression.

Data analysis revealed that there were no differences between cases and controls with regard to overall dietary practices or Fitzpatrick skin types.

Nor were there differences in time spent sunbathing or in the number of reported sunburn episodes either before or after diagnosis.

Although more relapsing patients reported using sunblock after the removal of their tumor than controls—91% vs. 85%—this difference was not statistically significant, said Dr. Newton Bishop of the Genetic Epidemiology Division, Cancer Research U.K., St. James's University Hospital, Leeds, England.

However, there were significant differences in vitamin D supplement use during the year prior to relapse, with 42% of controls and 28% of relapsing patients reporting that they took supplementary vitamin D. The odds ratio was 0.54 for relapse among those with a history of vitamin D supplement use, she said.

Serum vitamin D levels were significantly higher in those taking the supplement than in those who did not: a mean level of 54.3 nmol/L compared with 42.8 nmol/L. These measures confirmed patients' reports of taking the vitamin, she said.

VDR genotype results were available for 300 of the participants. None of the SNPs showed a significant association with relapse overall, but among patients who carried one or more copies of the variant Cdx-2 allele for increased VDR activity and expression, supplement use was associated with a highly significant reduced risk of relapse, with an odds ratio of 0.1.

Among patients who were homozygous for the wild-type variant of Taql associated with increased expression of VDR, there also was a significant reduction in risk of relapse, again with an odds ratio of 0.1.

“The observed protective effects of vitamin D intake and interaction with VDR genotype suggest that [this vitamin] is an important therapeutic candidate, which must be urgently evaluated further,” she said.

BOSTON — Severely obese women who underwent bariatric surgery and had major weight loss prior to pregnancy reduced the likelihood of macrosomia and subsequent obesity in their offspring, Dr. John G. Kral said at the annual meeting of NAASO, the Obesity Society.

What's more, the children of these mothers have been followed for 2–18 years and have no higher rate of obesity than does the larger age-matched background population in Quebec, where the study was done, he said.

The surgical procedure the women underwent was a pyloris-sparing biliopancreatic diversion (BPD), which is not only maldigestive but also malabsorptive. This of course raises concerns for pregnancy, with potential vitamin deficiencies, undernutrition, and low birth weight among the offspring, but the results have been reassuring, he said.

Dr. Kral and his coinvestigators from the department of surgery, Laval University, Quebec, followed a cohort of 45 children born before their mothers had surgery and 172 born after the surgery. The children are now aged 7 years or older, and in those born before surgery the prevalence of obesity is 60%, while among those born after the surgery the prevalence is 37%, said Dr. Kral of the State University of New York Health Science Center at Brooklyn.

According to the National Longitudinal Survey of Children and Youth in Canada, the overall prevalence of obesity among Canadian children in that age group is 38%.

Moreover, not only did the prevalence of obesity fall by 52% but also the prevalence of severe obesity fell by 45.1%, and there was no increase in low birth weight, he said.

Malabsorptive BPD surgery does not cause maternal stress or create “a famine situation in utero,” Dr. Kral said. Rather, it provides in utero benefits of energy homeostasis, euglycemia, and normalization of insulin and lipid levels, he said.

The odds ratio for obesity in children of very obese mothers is 60-fold, at least in part because of genetic factors, but by normalizing the fetal environment this surgery actually abrogates the genotype, he explained.

Dr. Kral and his coinvestigators had previously reported on a group of 783 women who underwent BPD and replied to a questionnaire that asked about pre- and postoperative pregnancies. Among the findings of that survey were that 82.6% of the women had a normal weight gain during postoperative pregnancy, the incidence of fetal macrosomia decreased from 34.8% to 7.7%, and the incidence of normal birth weight increased from 62.1% to 82.7%.

The investigators wrote, “We believe that the overall normalization of birth weights in these severely obese women is a consequence of the improved maternal physiological environment following BPD, including better glucose metabolism, lower blood pressure, and better hormonal function” (Obes. Surg. 2004;14:318–24).

BOSTON — Severely obese women who underwent bariatric surgery and had major weight loss prior to pregnancy reduced the likelihood of macrosomia and subsequent obesity in their offspring, Dr. John G. Kral said at the annual meeting of NAASO, the Obesity Society.

What's more, the children of these mothers have been followed for 2–18 years and have no higher rate of obesity than does the larger age-matched background population in Quebec, where the study was done, he said.

The surgical procedure the women underwent was a pyloris-sparing biliopancreatic diversion (BPD), which is not only maldigestive but also malabsorptive. This of course raises concerns for pregnancy, with potential vitamin deficiencies, undernutrition, and low birth weight among the offspring, but the results have been reassuring, he said.

Dr. Kral and his coinvestigators from the department of surgery, Laval University, Quebec, followed a cohort of 45 children born before their mothers had surgery and 172 born after the surgery. The children are now aged 7 years or older, and in those born before surgery the prevalence of obesity is 60%, while among those born after the surgery the prevalence is 37%, said Dr. Kral of the State University of New York Health Science Center at Brooklyn.

According to the National Longitudinal Survey of Children and Youth in Canada, the overall prevalence of obesity among Canadian children in that age group is 38%.

Moreover, not only did the prevalence of obesity fall by 52% but also the prevalence of severe obesity fell by 45.1%, and there was no increase in low birth weight, he said.

Malabsorptive BPD surgery does not cause maternal stress or create “a famine situation in utero,” Dr. Kral said. Rather, it provides in utero benefits of energy homeostasis, euglycemia, and normalization of insulin and lipid levels, he said.

The odds ratio for obesity in children of very obese mothers is 60-fold, at least in part because of genetic factors, but by normalizing the fetal environment this surgery actually abrogates the genotype, he explained.

Dr. Kral and his coinvestigators had previously reported on a group of 783 women who underwent BPD and replied to a questionnaire that asked about pre- and postoperative pregnancies. Among the findings of that survey were that 82.6% of the women had a normal weight gain during postoperative pregnancy, the incidence of fetal macrosomia decreased from 34.8% to 7.7%, and the incidence of normal birth weight increased from 62.1% to 82.7%.

The investigators wrote, “We believe that the overall normalization of birth weights in these severely obese women is a consequence of the improved maternal physiological environment following BPD, including better glucose metabolism, lower blood pressure, and better hormonal function” (Obes. Surg. 2004;14:318–24).

BOSTON — Severely obese women who underwent bariatric surgery and had major weight loss prior to pregnancy reduced the likelihood of macrosomia and subsequent obesity in their offspring, Dr. John G. Kral said at the annual meeting of NAASO, the Obesity Society.

What's more, the children of these mothers have been followed for 2–18 years and have no higher rate of obesity than does the larger age-matched background population in Quebec, where the study was done, he said.

The surgical procedure the women underwent was a pyloris-sparing biliopancreatic diversion (BPD), which is not only maldigestive but also malabsorptive. This of course raises concerns for pregnancy, with potential vitamin deficiencies, undernutrition, and low birth weight among the offspring, but the results have been reassuring, he said.

Dr. Kral and his coinvestigators from the department of surgery, Laval University, Quebec, followed a cohort of 45 children born before their mothers had surgery and 172 born after the surgery. The children are now aged 7 years or older, and in those born before surgery the prevalence of obesity is 60%, while among those born after the surgery the prevalence is 37%, said Dr. Kral of the State University of New York Health Science Center at Brooklyn.

According to the National Longitudinal Survey of Children and Youth in Canada, the overall prevalence of obesity among Canadian children in that age group is 38%.

Moreover, not only did the prevalence of obesity fall by 52% but also the prevalence of severe obesity fell by 45.1%, and there was no increase in low birth weight, he said.

Malabsorptive BPD surgery does not cause maternal stress or create “a famine situation in utero,” Dr. Kral said. Rather, it provides in utero benefits of energy homeostasis, euglycemia, and normalization of insulin and lipid levels, he said.

The odds ratio for obesity in children of very obese mothers is 60-fold, at least in part because of genetic factors, but by normalizing the fetal environment this surgery actually abrogates the genotype, he explained.

Dr. Kral and his coinvestigators had previously reported on a group of 783 women who underwent BPD and replied to a questionnaire that asked about pre- and postoperative pregnancies. Among the findings of that survey were that 82.6% of the women had a normal weight gain during postoperative pregnancy, the incidence of fetal macrosomia decreased from 34.8% to 7.7%, and the incidence of normal birth weight increased from 62.1% to 82.7%.

The investigators wrote, “We believe that the overall normalization of birth weights in these severely obese women is a consequence of the improved maternal physiological environment following BPD, including better glucose metabolism, lower blood pressure, and better hormonal function” (Obes. Surg. 2004;14:318–24).

WASHINGTON — Women with lupus are at increased risk for thrombosis, infection, and hematologic disorders, according to data from the large National Inpatient Survey, Dr. Megan E.B. Clowse reported at the annual meeting of the American College of Rheumatology.

The National Inpatient Survey (NIS), which is administered by the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, contains data from 1,000 hospitals nationwide. Out of more than 18.3 million pregnancy-related hospital admissions between 2000 and 2002 in the United States, 17,262 (0.01%) involved women with SLE, according to Dr. Clowse, a rheumatologist at Duke University, Durham, N.C.

Analysis of data from the NIS revealed that women with SLE who become pregnant were significantly more likely also to have other underlying medical conditions that are associated with adverse outcomes, including renal failure (odds ratio 35.8), antiphospholipid syndrome (odds ratio 31.9), hypertension (odds ratio 6.4) and diabetes (odds ratio 1.6).

They were also more likely to experience complications during pregnancy (see chart). More than one-third had cesarean births, and preeclampsia was three times higher among the SLE patients than among non-SLE women, at 23%. Eclampsia developed only in a small percentage of lupus patients (0.5%), but this was still four times more common than in nonaffected women.

Moreover, women in the survey with SLE had demographic factors that may predispose them to more medical problems. They were older, with a mean age of 30 years, compared with 27.5 years in the general pregnancy population, and more (20%) were African American than in the general pregnancy population, at 14%.

The observation that pregnancy poses risks to women with SLE is not surprising, Dr. Clowse wrote in a poster session. After all, lupus itself increases the risk of death in reproductive age women by up to 12 times, regardless of pregnancy, and also heightens the risk of infection, thrombosis, and hematologic complications.

But the absolute risk of death during pregnancy remains low, at 0.3%, while the annual mortality among SLE patients ranges from 0.8% to 3%.

“The risk of death during pregnancy may actually be lower than during nonpregnancy for SLE patients, because the sickest patients do not get pregnant,” she observed. Nonetheless, pregnancy does carry risk for patients with lupus, and they should be followed closely by a rheumatologist and an obstetrician who specializes in high-risk pregnancies.

Also, because of the risk of thrombosis, consideration should be given for all SLE pregnancies to have prophylaxis with low-dose aspirin, Dr. Clowse noted.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Women with lupus are at increased risk for thrombosis, infection, and hematologic disorders, according to data from the large National Inpatient Survey, Dr. Megan E.B. Clowse reported at the annual meeting of the American College of Rheumatology.

The National Inpatient Survey (NIS), which is administered by the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, contains data from 1,000 hospitals nationwide. Out of more than 18.3 million pregnancy-related hospital admissions between 2000 and 2002 in the United States, 17,262 (0.01%) involved women with SLE, according to Dr. Clowse, a rheumatologist at Duke University, Durham, N.C.

Analysis of data from the NIS revealed that women with SLE who become pregnant were significantly more likely also to have other underlying medical conditions that are associated with adverse outcomes, including renal failure (odds ratio 35.8), antiphospholipid syndrome (odds ratio 31.9), hypertension (odds ratio 6.4) and diabetes (odds ratio 1.6).

They were also more likely to experience complications during pregnancy (see chart). More than one-third had cesarean births, and preeclampsia was three times higher among the SLE patients than among non-SLE women, at 23%. Eclampsia developed only in a small percentage of lupus patients (0.5%), but this was still four times more common than in nonaffected women.

Moreover, women in the survey with SLE had demographic factors that may predispose them to more medical problems. They were older, with a mean age of 30 years, compared with 27.5 years in the general pregnancy population, and more (20%) were African American than in the general pregnancy population, at 14%.

The observation that pregnancy poses risks to women with SLE is not surprising, Dr. Clowse wrote in a poster session. After all, lupus itself increases the risk of death in reproductive age women by up to 12 times, regardless of pregnancy, and also heightens the risk of infection, thrombosis, and hematologic complications.

But the absolute risk of death during pregnancy remains low, at 0.3%, while the annual mortality among SLE patients ranges from 0.8% to 3%.

“The risk of death during pregnancy may actually be lower than during nonpregnancy for SLE patients, because the sickest patients do not get pregnant,” she observed. Nonetheless, pregnancy does carry risk for patients with lupus, and they should be followed closely by a rheumatologist and an obstetrician who specializes in high-risk pregnancies.

Also, because of the risk of thrombosis, consideration should be given for all SLE pregnancies to have prophylaxis with low-dose aspirin, Dr. Clowse noted.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Women with lupus are at increased risk for thrombosis, infection, and hematologic disorders, according to data from the large National Inpatient Survey, Dr. Megan E.B. Clowse reported at the annual meeting of the American College of Rheumatology.

The National Inpatient Survey (NIS), which is administered by the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, contains data from 1,000 hospitals nationwide. Out of more than 18.3 million pregnancy-related hospital admissions between 2000 and 2002 in the United States, 17,262 (0.01%) involved women with SLE, according to Dr. Clowse, a rheumatologist at Duke University, Durham, N.C.

Analysis of data from the NIS revealed that women with SLE who become pregnant were significantly more likely also to have other underlying medical conditions that are associated with adverse outcomes, including renal failure (odds ratio 35.8), antiphospholipid syndrome (odds ratio 31.9), hypertension (odds ratio 6.4) and diabetes (odds ratio 1.6).

They were also more likely to experience complications during pregnancy (see chart). More than one-third had cesarean births, and preeclampsia was three times higher among the SLE patients than among non-SLE women, at 23%. Eclampsia developed only in a small percentage of lupus patients (0.5%), but this was still four times more common than in nonaffected women.

Moreover, women in the survey with SLE had demographic factors that may predispose them to more medical problems. They were older, with a mean age of 30 years, compared with 27.5 years in the general pregnancy population, and more (20%) were African American than in the general pregnancy population, at 14%.

The observation that pregnancy poses risks to women with SLE is not surprising, Dr. Clowse wrote in a poster session. After all, lupus itself increases the risk of death in reproductive age women by up to 12 times, regardless of pregnancy, and also heightens the risk of infection, thrombosis, and hematologic complications.

But the absolute risk of death during pregnancy remains low, at 0.3%, while the annual mortality among SLE patients ranges from 0.8% to 3%.

“The risk of death during pregnancy may actually be lower than during nonpregnancy for SLE patients, because the sickest patients do not get pregnant,” she observed. Nonetheless, pregnancy does carry risk for patients with lupus, and they should be followed closely by a rheumatologist and an obstetrician who specializes in high-risk pregnancies.

Also, because of the risk of thrombosis, consideration should be given for all SLE pregnancies to have prophylaxis with low-dose aspirin, Dr. Clowse noted.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Baseline seropositivity for rheumatoid factor and anticyclic citrullinated peptide among patients with rheumatoid arthritis is associated with a more favorable response to treatment with rituximab, Dr. Paul P. Tak reported at the annual meeting of the American College of Rheumatology.

A post hoc analysis was undertaken to explore the relationship between baseline autoantibody status and rituximab therapy in patients who participated in the 24-week Randomized Evaluation of Long Term Efficacy of Rituximab (REFLEX) study, according to Dr. Tak of the University of Amsterdam.

In REFLEX, patients with long-standing RA who had inadequate responses to one or more anti-tumor necrosis factor (TNF)-α drugs were randomized to receive a course of intravenous rituximab, which consisted of two infusions of 1,000 mg each, separated by 2 weeks, or placebo. All patients also were on background methotrexate in doses of 10–25 mg/week.

Among 309 patients analyzed at week 24, there was a high degree of efficacy for those who were seropositive for either or both of the autoantibodies (see box). Baseline RF greater than 20 IU/mL and anti-CCP greater than 5 IU/mL were considered seropositive.

With regard to the lower level ACR 20 responses, seronegative patients on rituximab also achieved this level to a greater degree than did seronegative patients on placebo.

Seronegative patients receiving rituximab did not achieve greater ACR 50 or 70 responses, however. “This suggests that other mechanisms such as antigen presentation, T-cell co-stimulation, and cytokine release may account for low levels of response, with higher responses to rituximab therapy being mediated primarily by suppression of pathogenic autoantibodies,” Dr. Tak wrote in a poster session.

Dr. Tak disclosed that he received research grants and consulting fees from Roche Laborotories Inc.

WASHINGTON — Baseline seropositivity for rheumatoid factor and anticyclic citrullinated peptide among patients with rheumatoid arthritis is associated with a more favorable response to treatment with rituximab, Dr. Paul P. Tak reported at the annual meeting of the American College of Rheumatology.

A post hoc analysis was undertaken to explore the relationship between baseline autoantibody status and rituximab therapy in patients who participated in the 24-week Randomized Evaluation of Long Term Efficacy of Rituximab (REFLEX) study, according to Dr. Tak of the University of Amsterdam.

In REFLEX, patients with long-standing RA who had inadequate responses to one or more anti-tumor necrosis factor (TNF)-α drugs were randomized to receive a course of intravenous rituximab, which consisted of two infusions of 1,000 mg each, separated by 2 weeks, or placebo. All patients also were on background methotrexate in doses of 10–25 mg/week.

Among 309 patients analyzed at week 24, there was a high degree of efficacy for those who were seropositive for either or both of the autoantibodies (see box). Baseline RF greater than 20 IU/mL and anti-CCP greater than 5 IU/mL were considered seropositive.

With regard to the lower level ACR 20 responses, seronegative patients on rituximab also achieved this level to a greater degree than did seronegative patients on placebo.

Seronegative patients receiving rituximab did not achieve greater ACR 50 or 70 responses, however. “This suggests that other mechanisms such as antigen presentation, T-cell co-stimulation, and cytokine release may account for low levels of response, with higher responses to rituximab therapy being mediated primarily by suppression of pathogenic autoantibodies,” Dr. Tak wrote in a poster session.

Dr. Tak disclosed that he received research grants and consulting fees from Roche Laborotories Inc.

WASHINGTON — Baseline seropositivity for rheumatoid factor and anticyclic citrullinated peptide among patients with rheumatoid arthritis is associated with a more favorable response to treatment with rituximab, Dr. Paul P. Tak reported at the annual meeting of the American College of Rheumatology.

A post hoc analysis was undertaken to explore the relationship between baseline autoantibody status and rituximab therapy in patients who participated in the 24-week Randomized Evaluation of Long Term Efficacy of Rituximab (REFLEX) study, according to Dr. Tak of the University of Amsterdam.

In REFLEX, patients with long-standing RA who had inadequate responses to one or more anti-tumor necrosis factor (TNF)-α drugs were randomized to receive a course of intravenous rituximab, which consisted of two infusions of 1,000 mg each, separated by 2 weeks, or placebo. All patients also were on background methotrexate in doses of 10–25 mg/week.

Among 309 patients analyzed at week 24, there was a high degree of efficacy for those who were seropositive for either or both of the autoantibodies (see box). Baseline RF greater than 20 IU/mL and anti-CCP greater than 5 IU/mL were considered seropositive.

With regard to the lower level ACR 20 responses, seronegative patients on rituximab also achieved this level to a greater degree than did seronegative patients on placebo.

Seronegative patients receiving rituximab did not achieve greater ACR 50 or 70 responses, however. “This suggests that other mechanisms such as antigen presentation, T-cell co-stimulation, and cytokine release may account for low levels of response, with higher responses to rituximab therapy being mediated primarily by suppression of pathogenic autoantibodies,” Dr. Tak wrote in a poster session.

Dr. Tak disclosed that he received research grants and consulting fees from Roche Laborotories Inc.