Amy Rothman Schonfeld

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – With improvements in light sources, hand instrumentation, and energy devices, robot-assisted minimally invasive surgery now offers a level of precision and finesse for treating endometriosis that was not previously available, according to Dr. Arnold Advincula.

"We know that endometriosis tends to compromise anatomical spaces," he said. "Robot-assisted minimally invasive surgery allows you to dissect in the plane of the compromised tissue, thereby minimizing trauma, which is advantageous when dissecting around the ureter or bowel."

Photo Courtesy Dr. Arnold Advincula

Conventional laparoscopic techniques offer limited degrees of motion for the surgeon and 2-D visualization. With robot-assisted surgery, the surgeon sees a 3-D view of the operating field. Additionally, the "endowrist" laparoscopic instruments used in the da Vinci surgical system mimic the full range of human wrist movement, allowing the surgeon 7 degrees of movement compared with 4 degrees of movement with conventional or "straight-stick" laparoscopic surgery; the conventional approach is limited by the "fulcrum effect" in which the hands move left as the instrument tip moves right. With robotic-surgery, the instruments follow the exact movements of the surgeon’s hands. The instrumentation also filters tremors and scales motion, improving precision.

Robotic surgery also offers ergonomic advantages. The surgeon can sit with arms rested. If the surgeon’s arms become hyperextended or flexed during surgery, the arm controls can be temporarily disengaged from the instrument tips to allow a change to a more comfortable position.

Robotic surgery makes it possible to get around obstacles and offers such control that surgeons can carefully dissect and excise diseased tissue layer by layer, said Dr. Advincula, medical director of gynecologic robotics at the Celebration Health Endometriosis Center at Florida Hospital. Robot-assisted surgery can be particularly useful for deeply infiltrating endometriosis of the pelvic peritoneum or ovary (endometriomas). A major strength lies in the robotic system’s ability to be an excellent tool for anatomical surgical dissection. It also can be helpful when accessing difficult-to-reach areas, such as endometriosis within the rectovaginal septum, which can be quite challenging with rigid nonarticulating instrumentation, Dr. Advincula said at the annual congress of the Endometriosis Foundation of America.

In cases where safe peritoneal access cannot be accomplished or significant comorbidities preclude an endoscopic approach, robot-assisted surgery may not be useful.

One criticism of robot-assisted surgery is the lack of tactile cues (haptic feedback). In addition to changes in coloration, endometriosis can be fibrotic, nodular, or cystic and feel thicker than normal tissue, especially if it is infiltrative. Dr. Advincula said he relies on visual cues combined with the knowledge of anatomical structures and dissection planes when performing excisional surgery via robotics. He cautioned that several years of robotic surgery experience are needed to understand and overcome this limitation.

Outcomes research comparing traditional laparoscopic surgery and robotic-assisted endometriosis surgery is limited, he noted. ACOG’s 2009 Technology Assessment in Obstetrics and Gynecology No. 6 on robot-assisted surgery suggested that randomized trials were needed to compare the respective outcomes and costs of robot-assisted surgery with those of traditional laparoscopic, vaginal, or abdominal surgery, and to pinpoint the best applications of robotic technology (Obstet. Gynecol. 2009;114:1153-5). A systematic review published in 2011 (Int. J. Med. Robot. 2011 Dec. 9 [doi:10.1002/rcs.451]) identified only three case reports and one cohort study that used the da Vinci surgical system for endometriosis, and concluded that few studies had been published in the field to date and evidence regarding long-term outcomes was lacking.

In a not-yet-published review of the literature, Dr. Advincula and his colleagues found 21 publications, mostly single cases or case series and one comparative controlled cohort study. The literature is clearly lacking in the area of using robotics for endometriosis surgery, he said. That is why the Celebration Health Endometriosis Center is involved in a multicenter collaboration to track outcomes and determine where advantages and disadvantages exist. As robotic technology evolves, it must be critically evaluated to determine its appropriate applications in endometriosis surgery.

Another problem for patients is that access to surgeons well trained in both the management of endometriosis and the proper use of robotics in gynecologic surgery is limited. "Clearly, when you have 10-20 million women affected by the disease, you can’t have just a handful of people capable of treating the disease. We need skilled surgeons who understand reproductive medicine, are familiar with applying surgical principles to complex cases, and who work in a multidisciplinary fashion in a specialized center to take advantage of a technology like this," said Dr. Advincula.

He said he encourages gynecologists and surgeons who wish to learn more about robot-assisted gynecologic surgery to attend conferences and workshops, such as the World Robotic Gynecology Conference, which provides opportunities to engage in both hands-on training and classroom teaching. Other alternatives are working with a surgical mentor or completing a fellowship in minimally invasive surgery that incorporates the surgical management of endometriosis.

"In the right hands and within the right infrastructure, robotics has the potential to provide women better options and access to cutting-edge care, especially in the area of endometriosis surgery. But as a new surgical frontier, don’t be lulled into thinking robotics per se will make you a better surgeon without the proper training and skill set," cautioned Dr. Advincula.

He said he is a consultant for Cooper Surgical, Ethicon Women’s Health and Urology, and Intuitive Surgical, and that he has received royalties from Cooper Surgical.

NEW YORK – With improvements in light sources, hand instrumentation, and energy devices, robot-assisted minimally invasive surgery now offers a level of precision and finesse for treating endometriosis that was not previously available, according to Dr. Arnold Advincula.

"We know that endometriosis tends to compromise anatomical spaces," he said. "Robot-assisted minimally invasive surgery allows you to dissect in the plane of the compromised tissue, thereby minimizing trauma, which is advantageous when dissecting around the ureter or bowel."

Photo Courtesy Dr. Arnold Advincula

Conventional laparoscopic techniques offer limited degrees of motion for the surgeon and 2-D visualization. With robot-assisted surgery, the surgeon sees a 3-D view of the operating field. Additionally, the "endowrist" laparoscopic instruments used in the da Vinci surgical system mimic the full range of human wrist movement, allowing the surgeon 7 degrees of movement compared with 4 degrees of movement with conventional or "straight-stick" laparoscopic surgery; the conventional approach is limited by the "fulcrum effect" in which the hands move left as the instrument tip moves right. With robotic-surgery, the instruments follow the exact movements of the surgeon’s hands. The instrumentation also filters tremors and scales motion, improving precision.

Robotic surgery also offers ergonomic advantages. The surgeon can sit with arms rested. If the surgeon’s arms become hyperextended or flexed during surgery, the arm controls can be temporarily disengaged from the instrument tips to allow a change to a more comfortable position.

Robotic surgery makes it possible to get around obstacles and offers such control that surgeons can carefully dissect and excise diseased tissue layer by layer, said Dr. Advincula, medical director of gynecologic robotics at the Celebration Health Endometriosis Center at Florida Hospital. Robot-assisted surgery can be particularly useful for deeply infiltrating endometriosis of the pelvic peritoneum or ovary (endometriomas). A major strength lies in the robotic system’s ability to be an excellent tool for anatomical surgical dissection. It also can be helpful when accessing difficult-to-reach areas, such as endometriosis within the rectovaginal septum, which can be quite challenging with rigid nonarticulating instrumentation, Dr. Advincula said at the annual congress of the Endometriosis Foundation of America.

In cases where safe peritoneal access cannot be accomplished or significant comorbidities preclude an endoscopic approach, robot-assisted surgery may not be useful.

One criticism of robot-assisted surgery is the lack of tactile cues (haptic feedback). In addition to changes in coloration, endometriosis can be fibrotic, nodular, or cystic and feel thicker than normal tissue, especially if it is infiltrative. Dr. Advincula said he relies on visual cues combined with the knowledge of anatomical structures and dissection planes when performing excisional surgery via robotics. He cautioned that several years of robotic surgery experience are needed to understand and overcome this limitation.

Outcomes research comparing traditional laparoscopic surgery and robotic-assisted endometriosis surgery is limited, he noted. ACOG’s 2009 Technology Assessment in Obstetrics and Gynecology No. 6 on robot-assisted surgery suggested that randomized trials were needed to compare the respective outcomes and costs of robot-assisted surgery with those of traditional laparoscopic, vaginal, or abdominal surgery, and to pinpoint the best applications of robotic technology (Obstet. Gynecol. 2009;114:1153-5). A systematic review published in 2011 (Int. J. Med. Robot. 2011 Dec. 9 [doi:10.1002/rcs.451]) identified only three case reports and one cohort study that used the da Vinci surgical system for endometriosis, and concluded that few studies had been published in the field to date and evidence regarding long-term outcomes was lacking.

In a not-yet-published review of the literature, Dr. Advincula and his colleagues found 21 publications, mostly single cases or case series and one comparative controlled cohort study. The literature is clearly lacking in the area of using robotics for endometriosis surgery, he said. That is why the Celebration Health Endometriosis Center is involved in a multicenter collaboration to track outcomes and determine where advantages and disadvantages exist. As robotic technology evolves, it must be critically evaluated to determine its appropriate applications in endometriosis surgery.

Another problem for patients is that access to surgeons well trained in both the management of endometriosis and the proper use of robotics in gynecologic surgery is limited. "Clearly, when you have 10-20 million women affected by the disease, you can’t have just a handful of people capable of treating the disease. We need skilled surgeons who understand reproductive medicine, are familiar with applying surgical principles to complex cases, and who work in a multidisciplinary fashion in a specialized center to take advantage of a technology like this," said Dr. Advincula.

He said he encourages gynecologists and surgeons who wish to learn more about robot-assisted gynecologic surgery to attend conferences and workshops, such as the World Robotic Gynecology Conference, which provides opportunities to engage in both hands-on training and classroom teaching. Other alternatives are working with a surgical mentor or completing a fellowship in minimally invasive surgery that incorporates the surgical management of endometriosis.

"In the right hands and within the right infrastructure, robotics has the potential to provide women better options and access to cutting-edge care, especially in the area of endometriosis surgery. But as a new surgical frontier, don’t be lulled into thinking robotics per se will make you a better surgeon without the proper training and skill set," cautioned Dr. Advincula.

He said he is a consultant for Cooper Surgical, Ethicon Women’s Health and Urology, and Intuitive Surgical, and that he has received royalties from Cooper Surgical.

NEW YORK – With improvements in light sources, hand instrumentation, and energy devices, robot-assisted minimally invasive surgery now offers a level of precision and finesse for treating endometriosis that was not previously available, according to Dr. Arnold Advincula.

"We know that endometriosis tends to compromise anatomical spaces," he said. "Robot-assisted minimally invasive surgery allows you to dissect in the plane of the compromised tissue, thereby minimizing trauma, which is advantageous when dissecting around the ureter or bowel."

Photo Courtesy Dr. Arnold Advincula

Conventional laparoscopic techniques offer limited degrees of motion for the surgeon and 2-D visualization. With robot-assisted surgery, the surgeon sees a 3-D view of the operating field. Additionally, the "endowrist" laparoscopic instruments used in the da Vinci surgical system mimic the full range of human wrist movement, allowing the surgeon 7 degrees of movement compared with 4 degrees of movement with conventional or "straight-stick" laparoscopic surgery; the conventional approach is limited by the "fulcrum effect" in which the hands move left as the instrument tip moves right. With robotic-surgery, the instruments follow the exact movements of the surgeon’s hands. The instrumentation also filters tremors and scales motion, improving precision.

Robotic surgery also offers ergonomic advantages. The surgeon can sit with arms rested. If the surgeon’s arms become hyperextended or flexed during surgery, the arm controls can be temporarily disengaged from the instrument tips to allow a change to a more comfortable position.

Robotic surgery makes it possible to get around obstacles and offers such control that surgeons can carefully dissect and excise diseased tissue layer by layer, said Dr. Advincula, medical director of gynecologic robotics at the Celebration Health Endometriosis Center at Florida Hospital. Robot-assisted surgery can be particularly useful for deeply infiltrating endometriosis of the pelvic peritoneum or ovary (endometriomas). A major strength lies in the robotic system’s ability to be an excellent tool for anatomical surgical dissection. It also can be helpful when accessing difficult-to-reach areas, such as endometriosis within the rectovaginal septum, which can be quite challenging with rigid nonarticulating instrumentation, Dr. Advincula said at the annual congress of the Endometriosis Foundation of America.

In cases where safe peritoneal access cannot be accomplished or significant comorbidities preclude an endoscopic approach, robot-assisted surgery may not be useful.

One criticism of robot-assisted surgery is the lack of tactile cues (haptic feedback). In addition to changes in coloration, endometriosis can be fibrotic, nodular, or cystic and feel thicker than normal tissue, especially if it is infiltrative. Dr. Advincula said he relies on visual cues combined with the knowledge of anatomical structures and dissection planes when performing excisional surgery via robotics. He cautioned that several years of robotic surgery experience are needed to understand and overcome this limitation.

Outcomes research comparing traditional laparoscopic surgery and robotic-assisted endometriosis surgery is limited, he noted. ACOG’s 2009 Technology Assessment in Obstetrics and Gynecology No. 6 on robot-assisted surgery suggested that randomized trials were needed to compare the respective outcomes and costs of robot-assisted surgery with those of traditional laparoscopic, vaginal, or abdominal surgery, and to pinpoint the best applications of robotic technology (Obstet. Gynecol. 2009;114:1153-5). A systematic review published in 2011 (Int. J. Med. Robot. 2011 Dec. 9 [doi:10.1002/rcs.451]) identified only three case reports and one cohort study that used the da Vinci surgical system for endometriosis, and concluded that few studies had been published in the field to date and evidence regarding long-term outcomes was lacking.

In a not-yet-published review of the literature, Dr. Advincula and his colleagues found 21 publications, mostly single cases or case series and one comparative controlled cohort study. The literature is clearly lacking in the area of using robotics for endometriosis surgery, he said. That is why the Celebration Health Endometriosis Center is involved in a multicenter collaboration to track outcomes and determine where advantages and disadvantages exist. As robotic technology evolves, it must be critically evaluated to determine its appropriate applications in endometriosis surgery.

Another problem for patients is that access to surgeons well trained in both the management of endometriosis and the proper use of robotics in gynecologic surgery is limited. "Clearly, when you have 10-20 million women affected by the disease, you can’t have just a handful of people capable of treating the disease. We need skilled surgeons who understand reproductive medicine, are familiar with applying surgical principles to complex cases, and who work in a multidisciplinary fashion in a specialized center to take advantage of a technology like this," said Dr. Advincula.

He said he encourages gynecologists and surgeons who wish to learn more about robot-assisted gynecologic surgery to attend conferences and workshops, such as the World Robotic Gynecology Conference, which provides opportunities to engage in both hands-on training and classroom teaching. Other alternatives are working with a surgical mentor or completing a fellowship in minimally invasive surgery that incorporates the surgical management of endometriosis.

"In the right hands and within the right infrastructure, robotics has the potential to provide women better options and access to cutting-edge care, especially in the area of endometriosis surgery. But as a new surgical frontier, don’t be lulled into thinking robotics per se will make you a better surgeon without the proper training and skill set," cautioned Dr. Advincula.

He said he is a consultant for Cooper Surgical, Ethicon Women’s Health and Urology, and Intuitive Surgical, and that he has received royalties from Cooper Surgical.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

NEW YORK – New research indicates that self-reported endometriosis is associated with a significantly increased risk of clear-cell and endometrioid invasive ovarian cancers, said Stacey A. Missmer, Sc.D.

In addition, for the first time, low-grade serous invasive ovarian cancer also was linked to endometriosis. No association was found for mucinous or high-grade serous invasive ovarian cancer or borderline tumors of either subtype in this analysis of pooled data from 13 ovarian cancer case-control studies, according to Dr. Missmer, who described the findings at the annual congress of the Endometriosis Foundation of America, but was not involved in the study.

The findings, published in Lancet Oncology (2012;13:385-94), show that "clinicians need to be aware of the increased risk of specific ovarian cancer subtypes in women with endometriosis," wrote lead author Celeste Leigh Pearce, Ph.D., and her colleagues.

"The hope is that we will develop a risk stratification model that combines genetic and epidemiological risk to better stratify women into high-risk, intermediate-risk, and low-risk categories, allowing better individualization of prevention and early detection approaches such as risk-reduction surgery and screening," wrote Dr. Pearce of the gynecology department at the University of Southern California, Los Angeles, and her coauthors.

The 13 case-control studies, which were part of the Ovarian Cancer Association Consortium, included 13,226 controls and 7,911 women with invasive ovarian cancer. Of those, 818 controls (6.2%) and 738 women with ovarian cancer (9.3%) reported a history of endometriosis. There also were 1,907 women with borderline ovarian cancer, and 168 of these women (8.8%) reported a history of endometriosis.

"Clinicians need to be aware of the increased risk of specific ovarian cancer subtypes in women with endometriosis."

A threefold increased risk of clear-cell invasive ovarian cancer in patients with self-reported endometriosis (P less than .0001) was found. A twofold increased risk was noted for low-grade serous (P less than .0001) and endometrioid invasive ovarian cancers (P less than .0001). "On the basis of evidence, including the results of molecular studies, endometriosis should be thought of as a precursor lesion for clear-cell and endometrioid ovarian cancers, whereas the type of association with low-grade serous ovarian cancers requires further follow-up," wrote the authors.

No association was found between endometriosis and the risk of invasive mucinous or high-grade serous ovarian cancer or borderline tumors of either subtype.

For serous ovarian cancer, the association with endometriosis depends on the grade. The risk for the invasive low-grade serous ovarian cancer was significantly stronger than that for its high-grade counterpart (odds ratio, 1.94; 95% confidence interval, 1.21-3.11; P = .01). The authors suggested that this is an additional piece of evidence suggesting that the pathogenesis of low-grade and high-grade serous ovarian cancers might differ.

Commenting on the study, Dr. Missmer said that the absolute risk of ovarian cancer in women with endometriosis was small. For most patients in the studies, the endometriosis was self-reported and not pathologically confirmed, noted Dr. Missmer, who is the director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital, Boston. She said that the findings indicated three possible causal associations: endometriosis causes cancer, long-term treatment of endometriosis influences cancer risk, or both are independent pathologies with common risk factors.

In an accompanying comment published in Lancet Oncology (2012;13:326-8), Charlie Gourley, Ph.D., of the University of Edinburgh Cancer Research UK Centre, said that the main strengths of the study are its statistical power and robust methods, which give it the power to allow definitive ovarian cancer subgroup analysis. He remarked that the main truly novel finding was the association between the history of endometriosis and low-grade serous ovarian cancer, but he was somewhat surprised by the lack of association between serous borderline tumors and endometriosis.

"By identification of an association between particular histological subtypes and not to others, weight is added to the increasing evidence that these histological subtypes are distinct disease entities," wrote Dr. Gourley. He also suggested that while the results do not mandate targeted ovarian cancer screening of patients with endometriosis, such screening should be considered.

Dr. Missmer said she had no relevant financial disclosures. Dr. Pearce and Dr. Gourley likewise reported no conflicts of interest.

NEW YORK – New research indicates that self-reported endometriosis is associated with a significantly increased risk of clear-cell and endometrioid invasive ovarian cancers, said Stacey A. Missmer, Sc.D.

In addition, for the first time, low-grade serous invasive ovarian cancer also was linked to endometriosis. No association was found for mucinous or high-grade serous invasive ovarian cancer or borderline tumors of either subtype in this analysis of pooled data from 13 ovarian cancer case-control studies, according to Dr. Missmer, who described the findings at the annual congress of the Endometriosis Foundation of America, but was not involved in the study.

The findings, published in Lancet Oncology (2012;13:385-94), show that "clinicians need to be aware of the increased risk of specific ovarian cancer subtypes in women with endometriosis," wrote lead author Celeste Leigh Pearce, Ph.D., and her colleagues.

"The hope is that we will develop a risk stratification model that combines genetic and epidemiological risk to better stratify women into high-risk, intermediate-risk, and low-risk categories, allowing better individualization of prevention and early detection approaches such as risk-reduction surgery and screening," wrote Dr. Pearce of the gynecology department at the University of Southern California, Los Angeles, and her coauthors.

The 13 case-control studies, which were part of the Ovarian Cancer Association Consortium, included 13,226 controls and 7,911 women with invasive ovarian cancer. Of those, 818 controls (6.2%) and 738 women with ovarian cancer (9.3%) reported a history of endometriosis. There also were 1,907 women with borderline ovarian cancer, and 168 of these women (8.8%) reported a history of endometriosis.

"Clinicians need to be aware of the increased risk of specific ovarian cancer subtypes in women with endometriosis."

A threefold increased risk of clear-cell invasive ovarian cancer in patients with self-reported endometriosis (P less than .0001) was found. A twofold increased risk was noted for low-grade serous (P less than .0001) and endometrioid invasive ovarian cancers (P less than .0001). "On the basis of evidence, including the results of molecular studies, endometriosis should be thought of as a precursor lesion for clear-cell and endometrioid ovarian cancers, whereas the type of association with low-grade serous ovarian cancers requires further follow-up," wrote the authors.

No association was found between endometriosis and the risk of invasive mucinous or high-grade serous ovarian cancer or borderline tumors of either subtype.

For serous ovarian cancer, the association with endometriosis depends on the grade. The risk for the invasive low-grade serous ovarian cancer was significantly stronger than that for its high-grade counterpart (odds ratio, 1.94; 95% confidence interval, 1.21-3.11; P = .01). The authors suggested that this is an additional piece of evidence suggesting that the pathogenesis of low-grade and high-grade serous ovarian cancers might differ.

Commenting on the study, Dr. Missmer said that the absolute risk of ovarian cancer in women with endometriosis was small. For most patients in the studies, the endometriosis was self-reported and not pathologically confirmed, noted Dr. Missmer, who is the director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital, Boston. She said that the findings indicated three possible causal associations: endometriosis causes cancer, long-term treatment of endometriosis influences cancer risk, or both are independent pathologies with common risk factors.

In an accompanying comment published in Lancet Oncology (2012;13:326-8), Charlie Gourley, Ph.D., of the University of Edinburgh Cancer Research UK Centre, said that the main strengths of the study are its statistical power and robust methods, which give it the power to allow definitive ovarian cancer subgroup analysis. He remarked that the main truly novel finding was the association between the history of endometriosis and low-grade serous ovarian cancer, but he was somewhat surprised by the lack of association between serous borderline tumors and endometriosis.

"By identification of an association between particular histological subtypes and not to others, weight is added to the increasing evidence that these histological subtypes are distinct disease entities," wrote Dr. Gourley. He also suggested that while the results do not mandate targeted ovarian cancer screening of patients with endometriosis, such screening should be considered.

Dr. Missmer said she had no relevant financial disclosures. Dr. Pearce and Dr. Gourley likewise reported no conflicts of interest.

NEW YORK – New research indicates that self-reported endometriosis is associated with a significantly increased risk of clear-cell and endometrioid invasive ovarian cancers, said Stacey A. Missmer, Sc.D.

In addition, for the first time, low-grade serous invasive ovarian cancer also was linked to endometriosis. No association was found for mucinous or high-grade serous invasive ovarian cancer or borderline tumors of either subtype in this analysis of pooled data from 13 ovarian cancer case-control studies, according to Dr. Missmer, who described the findings at the annual congress of the Endometriosis Foundation of America, but was not involved in the study.

The findings, published in Lancet Oncology (2012;13:385-94), show that "clinicians need to be aware of the increased risk of specific ovarian cancer subtypes in women with endometriosis," wrote lead author Celeste Leigh Pearce, Ph.D., and her colleagues.

"The hope is that we will develop a risk stratification model that combines genetic and epidemiological risk to better stratify women into high-risk, intermediate-risk, and low-risk categories, allowing better individualization of prevention and early detection approaches such as risk-reduction surgery and screening," wrote Dr. Pearce of the gynecology department at the University of Southern California, Los Angeles, and her coauthors.

The 13 case-control studies, which were part of the Ovarian Cancer Association Consortium, included 13,226 controls and 7,911 women with invasive ovarian cancer. Of those, 818 controls (6.2%) and 738 women with ovarian cancer (9.3%) reported a history of endometriosis. There also were 1,907 women with borderline ovarian cancer, and 168 of these women (8.8%) reported a history of endometriosis.

"Clinicians need to be aware of the increased risk of specific ovarian cancer subtypes in women with endometriosis."

A threefold increased risk of clear-cell invasive ovarian cancer in patients with self-reported endometriosis (P less than .0001) was found. A twofold increased risk was noted for low-grade serous (P less than .0001) and endometrioid invasive ovarian cancers (P less than .0001). "On the basis of evidence, including the results of molecular studies, endometriosis should be thought of as a precursor lesion for clear-cell and endometrioid ovarian cancers, whereas the type of association with low-grade serous ovarian cancers requires further follow-up," wrote the authors.

No association was found between endometriosis and the risk of invasive mucinous or high-grade serous ovarian cancer or borderline tumors of either subtype.

For serous ovarian cancer, the association with endometriosis depends on the grade. The risk for the invasive low-grade serous ovarian cancer was significantly stronger than that for its high-grade counterpart (odds ratio, 1.94; 95% confidence interval, 1.21-3.11; P = .01). The authors suggested that this is an additional piece of evidence suggesting that the pathogenesis of low-grade and high-grade serous ovarian cancers might differ.

Commenting on the study, Dr. Missmer said that the absolute risk of ovarian cancer in women with endometriosis was small. For most patients in the studies, the endometriosis was self-reported and not pathologically confirmed, noted Dr. Missmer, who is the director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital, Boston. She said that the findings indicated three possible causal associations: endometriosis causes cancer, long-term treatment of endometriosis influences cancer risk, or both are independent pathologies with common risk factors.

In an accompanying comment published in Lancet Oncology (2012;13:326-8), Charlie Gourley, Ph.D., of the University of Edinburgh Cancer Research UK Centre, said that the main strengths of the study are its statistical power and robust methods, which give it the power to allow definitive ovarian cancer subgroup analysis. He remarked that the main truly novel finding was the association between the history of endometriosis and low-grade serous ovarian cancer, but he was somewhat surprised by the lack of association between serous borderline tumors and endometriosis.

"By identification of an association between particular histological subtypes and not to others, weight is added to the increasing evidence that these histological subtypes are distinct disease entities," wrote Dr. Gourley. He also suggested that while the results do not mandate targeted ovarian cancer screening of patients with endometriosis, such screening should be considered.

Dr. Missmer said she had no relevant financial disclosures. Dr. Pearce and Dr. Gourley likewise reported no conflicts of interest.

NEW YORK – Kidney function may be the single best determinant of outcome in Henoch-Schönlein purpura, according to Dr. Philip Kahn.

Although only 1%-3% of patients develop end-stage renal disease, Henoch-Schönlein purpura (HSP) accounts for up to 20% of children on dialysis, Dr. Kahn said at a meeting sponsored by New York University.

The most common form of vasculitis in children, HSP is generally self-limiting. "Most renal manifestations of HSP will resolve spontaneously. A minority of patients with HSP will develop nephrotic-range proteinuria and elevated creatinine, with or without hypertension," according to Dr. Kahn, a pediatric rheumatologist affiliated with the New York University Langone Medical Center. "This increases the risk of progressive disease, and necessitates dialysis for a small minority of these patients."

About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

HSP may account for about one-half of all vasculitis cases in the United States. A full 90% of HSP cases present during childhood, with a mean age of onset of 4-7 years. The characteristic clinical features of HSP are nephritis, purpura, arthritis/arthralgia, and abdominal pain. Symptoms typically last for about 4 weeks.

Between 20% and 54% of HSP patients have glomerulonephritis, said Dr. Kahn. Many patients will have asymptomatic hematuria, with mild or no proteinuria. "We see a gamut of urinalysis abnormalities: 14% have isolated hematuria, 9% have isolated proteinuria, 56% have both hematuria and proteinuria, 20% have nephrotic syndrome, and 1% have nephrotic-nephritic syndrome," said Dr. Kahn. For 85% of patients, nephritis develops within the first 4 weeks.

Patients with transient hematuria and proteinuria generally have an excellent prognosis, he said, and renal symptoms usually resolve spontaneously. However, counterintuitively up to 20% of patients who develop mild proteinuria may still have a poor outcome with advanced renal disease on biopsy, emphasizing that the biopsy may not mirror the clinical symptoms. Of those with nephrotic-range proteinuria and elevated creatinine levels, with or without hypertension, 1%-3% develop progressive disease. "Studies have shown that long-term persistent renal abnormalities are more likely to present with nephrotic syndrome, yet symptoms do resolve for half of these patients, no matter what the treatment," said Dr. Kahn.

A recent report indicated that 8 years after HSP, those with nephritis at the onset of HSP had more than a threefold increased risk of hypertension and/or urine abnormalities, as well as an increased risk of pregnancy-related proteinuria.

Typically, patients with overt renal disease are managed by nephrologists. About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

To monitor renal involvement in HSP patients, Dr. Kahn recommended doing urinalysis dipstick and blood pressure monitoring weekly for the first 1-2 months after diagnosis, then monthly for the next 6 months, followed by every other month until the completion of 1 year. Neither biopsy nor symptoms reliably predict outcome, said Dr. Kahn. Pathologic findings of HSP appear identical to those of IgA nephropathy, with histologic findings including mesangial proliferation, focal and segmental proliferation, and severe crescentic glomerulonephritis. Electron dense deposits can be seen in mesangial areas under electron microscopy. Immunofluorescence can reveal large, globular mesangial IgA deposits, which occasionally also include IgG and IgM. The presence of crescents may not necessarily foretell poor prognosis, although generally patients with greater than 50% crescents do not recover fully.

There is no well-accepted treatment for HSP-related nephritis. Most evidence comes from small retrospective cohort studies, with marked differences in the definitions of renal involvement, dosing regimens, and glucocorticoid modes of delivery. Variable results have been reported for cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, antiplatelet therapy, and plasmapheresis.

Whether glucocorticoids can be used to treat or prevent HSP-related nephritis is controversial. A meta-analysis of patients treated between 1956 and 2007 comparing outcomes of prednisone treatment versus supportive care suggested that the use of corticosteroids early in the disease reduced the risk of developing persistent renal disease (Pediatrics 2007;120:1079-87). On the other hand, a Cochrane review of 10 randomized, controlled trials that included 1,230 patients failed to demonstrate any benefit of prednisone in preventing serious long-term kidney disease in HSP (Arch. Dis. Child. 2009;94:132-7).

HSP may recur in about one-third of patients within 4 months, with the second bout being milder and briefer than the first. There is some evidence that the risk of recurrence increases in those with more severe disease, including patients who have had nephritis, an elevated erythrocyte sedimentation rate, or steroid treatment.

Renal impairment in HSP patients may also resurface during pregnancy. In a 24-year follow-up of patients who had severe HSP and glomerulonephritis at onset, 16 of 23 pregnancies (70%) were complicated by hypertension, proteinuria, or both, and 56% of the 9 women with complicated pregnancies had a poor renal outcome (Lancet 2002;360:666-70). For this reason, all women with HSP renal symptoms, however mild, should be carefully monitored during and after pregnancy.

Dr. Kahn said he had no relevant financial disclosures.

NEW YORK – Kidney function may be the single best determinant of outcome in Henoch-Schönlein purpura, according to Dr. Philip Kahn.

Although only 1%-3% of patients develop end-stage renal disease, Henoch-Schönlein purpura (HSP) accounts for up to 20% of children on dialysis, Dr. Kahn said at a meeting sponsored by New York University.

The most common form of vasculitis in children, HSP is generally self-limiting. "Most renal manifestations of HSP will resolve spontaneously. A minority of patients with HSP will develop nephrotic-range proteinuria and elevated creatinine, with or without hypertension," according to Dr. Kahn, a pediatric rheumatologist affiliated with the New York University Langone Medical Center. "This increases the risk of progressive disease, and necessitates dialysis for a small minority of these patients."

About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

HSP may account for about one-half of all vasculitis cases in the United States. A full 90% of HSP cases present during childhood, with a mean age of onset of 4-7 years. The characteristic clinical features of HSP are nephritis, purpura, arthritis/arthralgia, and abdominal pain. Symptoms typically last for about 4 weeks.

Between 20% and 54% of HSP patients have glomerulonephritis, said Dr. Kahn. Many patients will have asymptomatic hematuria, with mild or no proteinuria. "We see a gamut of urinalysis abnormalities: 14% have isolated hematuria, 9% have isolated proteinuria, 56% have both hematuria and proteinuria, 20% have nephrotic syndrome, and 1% have nephrotic-nephritic syndrome," said Dr. Kahn. For 85% of patients, nephritis develops within the first 4 weeks.

Patients with transient hematuria and proteinuria generally have an excellent prognosis, he said, and renal symptoms usually resolve spontaneously. However, counterintuitively up to 20% of patients who develop mild proteinuria may still have a poor outcome with advanced renal disease on biopsy, emphasizing that the biopsy may not mirror the clinical symptoms. Of those with nephrotic-range proteinuria and elevated creatinine levels, with or without hypertension, 1%-3% develop progressive disease. "Studies have shown that long-term persistent renal abnormalities are more likely to present with nephrotic syndrome, yet symptoms do resolve for half of these patients, no matter what the treatment," said Dr. Kahn.

A recent report indicated that 8 years after HSP, those with nephritis at the onset of HSP had more than a threefold increased risk of hypertension and/or urine abnormalities, as well as an increased risk of pregnancy-related proteinuria.

Typically, patients with overt renal disease are managed by nephrologists. About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

To monitor renal involvement in HSP patients, Dr. Kahn recommended doing urinalysis dipstick and blood pressure monitoring weekly for the first 1-2 months after diagnosis, then monthly for the next 6 months, followed by every other month until the completion of 1 year. Neither biopsy nor symptoms reliably predict outcome, said Dr. Kahn. Pathologic findings of HSP appear identical to those of IgA nephropathy, with histologic findings including mesangial proliferation, focal and segmental proliferation, and severe crescentic glomerulonephritis. Electron dense deposits can be seen in mesangial areas under electron microscopy. Immunofluorescence can reveal large, globular mesangial IgA deposits, which occasionally also include IgG and IgM. The presence of crescents may not necessarily foretell poor prognosis, although generally patients with greater than 50% crescents do not recover fully.

There is no well-accepted treatment for HSP-related nephritis. Most evidence comes from small retrospective cohort studies, with marked differences in the definitions of renal involvement, dosing regimens, and glucocorticoid modes of delivery. Variable results have been reported for cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, antiplatelet therapy, and plasmapheresis.

Whether glucocorticoids can be used to treat or prevent HSP-related nephritis is controversial. A meta-analysis of patients treated between 1956 and 2007 comparing outcomes of prednisone treatment versus supportive care suggested that the use of corticosteroids early in the disease reduced the risk of developing persistent renal disease (Pediatrics 2007;120:1079-87). On the other hand, a Cochrane review of 10 randomized, controlled trials that included 1,230 patients failed to demonstrate any benefit of prednisone in preventing serious long-term kidney disease in HSP (Arch. Dis. Child. 2009;94:132-7).

HSP may recur in about one-third of patients within 4 months, with the second bout being milder and briefer than the first. There is some evidence that the risk of recurrence increases in those with more severe disease, including patients who have had nephritis, an elevated erythrocyte sedimentation rate, or steroid treatment.

Renal impairment in HSP patients may also resurface during pregnancy. In a 24-year follow-up of patients who had severe HSP and glomerulonephritis at onset, 16 of 23 pregnancies (70%) were complicated by hypertension, proteinuria, or both, and 56% of the 9 women with complicated pregnancies had a poor renal outcome (Lancet 2002;360:666-70). For this reason, all women with HSP renal symptoms, however mild, should be carefully monitored during and after pregnancy.

Dr. Kahn said he had no relevant financial disclosures.

NEW YORK – Kidney function may be the single best determinant of outcome in Henoch-Schönlein purpura, according to Dr. Philip Kahn.

Although only 1%-3% of patients develop end-stage renal disease, Henoch-Schönlein purpura (HSP) accounts for up to 20% of children on dialysis, Dr. Kahn said at a meeting sponsored by New York University.

The most common form of vasculitis in children, HSP is generally self-limiting. "Most renal manifestations of HSP will resolve spontaneously. A minority of patients with HSP will develop nephrotic-range proteinuria and elevated creatinine, with or without hypertension," according to Dr. Kahn, a pediatric rheumatologist affiliated with the New York University Langone Medical Center. "This increases the risk of progressive disease, and necessitates dialysis for a small minority of these patients."

About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

HSP may account for about one-half of all vasculitis cases in the United States. A full 90% of HSP cases present during childhood, with a mean age of onset of 4-7 years. The characteristic clinical features of HSP are nephritis, purpura, arthritis/arthralgia, and abdominal pain. Symptoms typically last for about 4 weeks.

Between 20% and 54% of HSP patients have glomerulonephritis, said Dr. Kahn. Many patients will have asymptomatic hematuria, with mild or no proteinuria. "We see a gamut of urinalysis abnormalities: 14% have isolated hematuria, 9% have isolated proteinuria, 56% have both hematuria and proteinuria, 20% have nephrotic syndrome, and 1% have nephrotic-nephritic syndrome," said Dr. Kahn. For 85% of patients, nephritis develops within the first 4 weeks.

Patients with transient hematuria and proteinuria generally have an excellent prognosis, he said, and renal symptoms usually resolve spontaneously. However, counterintuitively up to 20% of patients who develop mild proteinuria may still have a poor outcome with advanced renal disease on biopsy, emphasizing that the biopsy may not mirror the clinical symptoms. Of those with nephrotic-range proteinuria and elevated creatinine levels, with or without hypertension, 1%-3% develop progressive disease. "Studies have shown that long-term persistent renal abnormalities are more likely to present with nephrotic syndrome, yet symptoms do resolve for half of these patients, no matter what the treatment," said Dr. Kahn.

A recent report indicated that 8 years after HSP, those with nephritis at the onset of HSP had more than a threefold increased risk of hypertension and/or urine abnormalities, as well as an increased risk of pregnancy-related proteinuria.

Typically, patients with overt renal disease are managed by nephrologists. About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

To monitor renal involvement in HSP patients, Dr. Kahn recommended doing urinalysis dipstick and blood pressure monitoring weekly for the first 1-2 months after diagnosis, then monthly for the next 6 months, followed by every other month until the completion of 1 year. Neither biopsy nor symptoms reliably predict outcome, said Dr. Kahn. Pathologic findings of HSP appear identical to those of IgA nephropathy, with histologic findings including mesangial proliferation, focal and segmental proliferation, and severe crescentic glomerulonephritis. Electron dense deposits can be seen in mesangial areas under electron microscopy. Immunofluorescence can reveal large, globular mesangial IgA deposits, which occasionally also include IgG and IgM. The presence of crescents may not necessarily foretell poor prognosis, although generally patients with greater than 50% crescents do not recover fully.

There is no well-accepted treatment for HSP-related nephritis. Most evidence comes from small retrospective cohort studies, with marked differences in the definitions of renal involvement, dosing regimens, and glucocorticoid modes of delivery. Variable results have been reported for cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, antiplatelet therapy, and plasmapheresis.

Whether glucocorticoids can be used to treat or prevent HSP-related nephritis is controversial. A meta-analysis of patients treated between 1956 and 2007 comparing outcomes of prednisone treatment versus supportive care suggested that the use of corticosteroids early in the disease reduced the risk of developing persistent renal disease (Pediatrics 2007;120:1079-87). On the other hand, a Cochrane review of 10 randomized, controlled trials that included 1,230 patients failed to demonstrate any benefit of prednisone in preventing serious long-term kidney disease in HSP (Arch. Dis. Child. 2009;94:132-7).

HSP may recur in about one-third of patients within 4 months, with the second bout being milder and briefer than the first. There is some evidence that the risk of recurrence increases in those with more severe disease, including patients who have had nephritis, an elevated erythrocyte sedimentation rate, or steroid treatment.

Renal impairment in HSP patients may also resurface during pregnancy. In a 24-year follow-up of patients who had severe HSP and glomerulonephritis at onset, 16 of 23 pregnancies (70%) were complicated by hypertension, proteinuria, or both, and 56% of the 9 women with complicated pregnancies had a poor renal outcome (Lancet 2002;360:666-70). For this reason, all women with HSP renal symptoms, however mild, should be carefully monitored during and after pregnancy.

Dr. Kahn said he had no relevant financial disclosures.

NEW YORK – Poststreptococcal reactive arthritis in a child means fewer cardiac sequelae and less need for prophylactic antibiotics, making it worth looking for when the obvious diagnosis seems to be acute rheumatic fever, according to Dr. Stanford T. Shulman, who spoke at a meeting sponsored by New York University.

"There are several reasons why it is important to differentiate poststreptococcal reactive arthritis from [acute rheumatic fever (ARF)]," explained Dr. Shulman, chief of infectious diseases at the Children’s Memorial Hospital in Chicago and the Virginia H. Rogers Professor of Pediatric Infectious Diseases at Northwestern University, Chicago. "Rheumatic fever frequently recurs and requires long-term antibiotics to prevent recurrence."

Not fulfilling the Jones criteria is one of the first clues of PSRA. The updated 1992 Jones criteria specifies that the diagnosis of ARF relies on the presence of two of the major criteria (that is, carditis, polyarthritis of large joints, chorea, erythema marginatum, and subcutaneous nodules) or one major and two minor (arthralgia, fever, elevation of the acute phase reactants C-reactive protein and erythrocyte sedimentation rate, prolonged PR interval on an echocardiogram) criteria, plus evidence of a recent group A streptococcal infection.

Heart involvement is controversial in PSRA and if it occurs, it is quite rare, said Dr. Shulman. But carditis is the common in acute rheumatic fever and accounts for its importance. Patients with ARF who have carditis characteristically have valvulitis with mitral regurgitation most commonly, followed by mitral and aortic regurgitation. Aortic regurgitation alone is rare in ARF. Patients with only pericarditis and/or myocarditis without valvulitis do not have rheumatic heart disease. After reviewing eight clinical reports representing 120 clinical cases of PSRA, Dr. Shulman concluded that it was questionable whether carditis can occur in children with PSRA, but that carditis was completely absent in several series of adults with PSRA.

There are other ways to differentiate PSRA from ARF. Symptoms of PSRA have an acute onset, usually less than 2 weeks from the time of streptococcal infection, compared with 2-3 weeks for ARF. Arthritic symptoms are brief with ARF (about 6 days). But, in PSRA, they can last for 8 weeks or longer and may be recurrent. In PSRA, the arthritis can affect any joint, large or small, and symptoms may be symmetric or asymmetric with axial involvement. In contrast, ARF arthritis is not symmetric and does not usually affect small joints or the axis. With ARF, arthritic symptoms typically migrate but are non-migratory with PSRA. Patients in either group may complain of morning stiffness.

Response to treatment is another way to distinguish the two. If a patient with poststreptococcal arthritis responds poorly or not at all to NSAIDs, then the diagnosis is much more likely to be PSRA; ARF patients respond very promptly to such treatment, says Dr. Shulman.

Both the American Heart Association and the American Academy of Pediatrics recommend that patients with acute rheumatic fever receive antistreptococcus prophylaxis until they are 21 years old. The 2009 American Heart Association Scientific Statement recommends that patients with PSRA should be observed carefully for several months for clinical evidence of carditis and should receive up to 1 year of secondary prophylaxis after the onset of symptoms and discontinue if no findings of carditis are apparent. Dr. Shulman said he gives either IM penicillin every 4 weeks or twice daily oral penicillin for 1-2 years, which should be discontinued if no evidence of valvular disease appears. If valvular disease is found, the patient is then considered to have ARF and should continue to receive long-term secondary prophylaxis.

The good news is that there has been a dramatic decrease in the number of rheumatogenic strains of group A streptococcus in circulation, says Dr. Shulman. By comparing the prevalence of rheumatogenic and nonrheumatogenic strains of group A strep in samples from 468 children with pharyngitis taken in 1961-1968 with samples from 450 children with pharyngitis taken in 2000-2004, Dr. Shulman found that in the 1960s, two-thirds of group A strep strains in circulation were rheumatogenic, while in the later sample only one-quarter were. He and his colleagues recently completed a large 13-center U.S. and Canadian study analyzing the subtypes of group A streptococcal infection more recently in circulation through the use of M protein typing.

Dr. Shulman is a member of Merck’s speakers bureau and has research support from Quidel.

NEW YORK – Poststreptococcal reactive arthritis in a child means fewer cardiac sequelae and less need for prophylactic antibiotics, making it worth looking for when the obvious diagnosis seems to be acute rheumatic fever, according to Dr. Stanford T. Shulman, who spoke at a meeting sponsored by New York University.

"There are several reasons why it is important to differentiate poststreptococcal reactive arthritis from [acute rheumatic fever (ARF)]," explained Dr. Shulman, chief of infectious diseases at the Children’s Memorial Hospital in Chicago and the Virginia H. Rogers Professor of Pediatric Infectious Diseases at Northwestern University, Chicago. "Rheumatic fever frequently recurs and requires long-term antibiotics to prevent recurrence."

Not fulfilling the Jones criteria is one of the first clues of PSRA. The updated 1992 Jones criteria specifies that the diagnosis of ARF relies on the presence of two of the major criteria (that is, carditis, polyarthritis of large joints, chorea, erythema marginatum, and subcutaneous nodules) or one major and two minor (arthralgia, fever, elevation of the acute phase reactants C-reactive protein and erythrocyte sedimentation rate, prolonged PR interval on an echocardiogram) criteria, plus evidence of a recent group A streptococcal infection.

Heart involvement is controversial in PSRA and if it occurs, it is quite rare, said Dr. Shulman. But carditis is the common in acute rheumatic fever and accounts for its importance. Patients with ARF who have carditis characteristically have valvulitis with mitral regurgitation most commonly, followed by mitral and aortic regurgitation. Aortic regurgitation alone is rare in ARF. Patients with only pericarditis and/or myocarditis without valvulitis do not have rheumatic heart disease. After reviewing eight clinical reports representing 120 clinical cases of PSRA, Dr. Shulman concluded that it was questionable whether carditis can occur in children with PSRA, but that carditis was completely absent in several series of adults with PSRA.

There are other ways to differentiate PSRA from ARF. Symptoms of PSRA have an acute onset, usually less than 2 weeks from the time of streptococcal infection, compared with 2-3 weeks for ARF. Arthritic symptoms are brief with ARF (about 6 days). But, in PSRA, they can last for 8 weeks or longer and may be recurrent. In PSRA, the arthritis can affect any joint, large or small, and symptoms may be symmetric or asymmetric with axial involvement. In contrast, ARF arthritis is not symmetric and does not usually affect small joints or the axis. With ARF, arthritic symptoms typically migrate but are non-migratory with PSRA. Patients in either group may complain of morning stiffness.

Response to treatment is another way to distinguish the two. If a patient with poststreptococcal arthritis responds poorly or not at all to NSAIDs, then the diagnosis is much more likely to be PSRA; ARF patients respond very promptly to such treatment, says Dr. Shulman.

Both the American Heart Association and the American Academy of Pediatrics recommend that patients with acute rheumatic fever receive antistreptococcus prophylaxis until they are 21 years old. The 2009 American Heart Association Scientific Statement recommends that patients with PSRA should be observed carefully for several months for clinical evidence of carditis and should receive up to 1 year of secondary prophylaxis after the onset of symptoms and discontinue if no findings of carditis are apparent. Dr. Shulman said he gives either IM penicillin every 4 weeks or twice daily oral penicillin for 1-2 years, which should be discontinued if no evidence of valvular disease appears. If valvular disease is found, the patient is then considered to have ARF and should continue to receive long-term secondary prophylaxis.

The good news is that there has been a dramatic decrease in the number of rheumatogenic strains of group A streptococcus in circulation, says Dr. Shulman. By comparing the prevalence of rheumatogenic and nonrheumatogenic strains of group A strep in samples from 468 children with pharyngitis taken in 1961-1968 with samples from 450 children with pharyngitis taken in 2000-2004, Dr. Shulman found that in the 1960s, two-thirds of group A strep strains in circulation were rheumatogenic, while in the later sample only one-quarter were. He and his colleagues recently completed a large 13-center U.S. and Canadian study analyzing the subtypes of group A streptococcal infection more recently in circulation through the use of M protein typing.

Dr. Shulman is a member of Merck’s speakers bureau and has research support from Quidel.

NEW YORK – Poststreptococcal reactive arthritis in a child means fewer cardiac sequelae and less need for prophylactic antibiotics, making it worth looking for when the obvious diagnosis seems to be acute rheumatic fever, according to Dr. Stanford T. Shulman, who spoke at a meeting sponsored by New York University.

"There are several reasons why it is important to differentiate poststreptococcal reactive arthritis from [acute rheumatic fever (ARF)]," explained Dr. Shulman, chief of infectious diseases at the Children’s Memorial Hospital in Chicago and the Virginia H. Rogers Professor of Pediatric Infectious Diseases at Northwestern University, Chicago. "Rheumatic fever frequently recurs and requires long-term antibiotics to prevent recurrence."

Not fulfilling the Jones criteria is one of the first clues of PSRA. The updated 1992 Jones criteria specifies that the diagnosis of ARF relies on the presence of two of the major criteria (that is, carditis, polyarthritis of large joints, chorea, erythema marginatum, and subcutaneous nodules) or one major and two minor (arthralgia, fever, elevation of the acute phase reactants C-reactive protein and erythrocyte sedimentation rate, prolonged PR interval on an echocardiogram) criteria, plus evidence of a recent group A streptococcal infection.

Heart involvement is controversial in PSRA and if it occurs, it is quite rare, said Dr. Shulman. But carditis is the common in acute rheumatic fever and accounts for its importance. Patients with ARF who have carditis characteristically have valvulitis with mitral regurgitation most commonly, followed by mitral and aortic regurgitation. Aortic regurgitation alone is rare in ARF. Patients with only pericarditis and/or myocarditis without valvulitis do not have rheumatic heart disease. After reviewing eight clinical reports representing 120 clinical cases of PSRA, Dr. Shulman concluded that it was questionable whether carditis can occur in children with PSRA, but that carditis was completely absent in several series of adults with PSRA.

There are other ways to differentiate PSRA from ARF. Symptoms of PSRA have an acute onset, usually less than 2 weeks from the time of streptococcal infection, compared with 2-3 weeks for ARF. Arthritic symptoms are brief with ARF (about 6 days). But, in PSRA, they can last for 8 weeks or longer and may be recurrent. In PSRA, the arthritis can affect any joint, large or small, and symptoms may be symmetric or asymmetric with axial involvement. In contrast, ARF arthritis is not symmetric and does not usually affect small joints or the axis. With ARF, arthritic symptoms typically migrate but are non-migratory with PSRA. Patients in either group may complain of morning stiffness.

Response to treatment is another way to distinguish the two. If a patient with poststreptococcal arthritis responds poorly or not at all to NSAIDs, then the diagnosis is much more likely to be PSRA; ARF patients respond very promptly to such treatment, says Dr. Shulman.

Both the American Heart Association and the American Academy of Pediatrics recommend that patients with acute rheumatic fever receive antistreptococcus prophylaxis until they are 21 years old. The 2009 American Heart Association Scientific Statement recommends that patients with PSRA should be observed carefully for several months for clinical evidence of carditis and should receive up to 1 year of secondary prophylaxis after the onset of symptoms and discontinue if no findings of carditis are apparent. Dr. Shulman said he gives either IM penicillin every 4 weeks or twice daily oral penicillin for 1-2 years, which should be discontinued if no evidence of valvular disease appears. If valvular disease is found, the patient is then considered to have ARF and should continue to receive long-term secondary prophylaxis.

The good news is that there has been a dramatic decrease in the number of rheumatogenic strains of group A streptococcus in circulation, says Dr. Shulman. By comparing the prevalence of rheumatogenic and nonrheumatogenic strains of group A strep in samples from 468 children with pharyngitis taken in 1961-1968 with samples from 450 children with pharyngitis taken in 2000-2004, Dr. Shulman found that in the 1960s, two-thirds of group A strep strains in circulation were rheumatogenic, while in the later sample only one-quarter were. He and his colleagues recently completed a large 13-center U.S. and Canadian study analyzing the subtypes of group A streptococcal infection more recently in circulation through the use of M protein typing.

Dr. Shulman is a member of Merck’s speakers bureau and has research support from Quidel.

NEW YORK – An intensive program that includes physical, occupational, and psychological therapy can help most children suffering from pain amplification syndrome to become fully functional within the first 1-2 weeks of treatment and pain free within the first month, according to Dr. David D. Sherry, who spoke at a meeting sponsored by the New York University. The improvements tend to be durable and relapses resolve quickly, often through self care.

A very painful medical condition, amplified musculoskeletal pain or reflex neurovascular dystrophy (RND) usually affects a limb but can cause pain anywhere on the body. Some children have pain all over and a few have intermittent attacks of pain. "The pain these children experience, however, is much more intense than one would normally expect because the pain signal is amplified," according to Dr. Sherry, chief of the rheumatology section at the Children’s Hospital of Philadelphia.

Dr. Sherry described several of the 1,900 cases he has seen in his practice, among them a 12-year-old girl who had banged her foot during basketball. Her foot was cold and blue 3 days later, she could not wear a sock, and she was on crutches. Another 12-year-old patient had fallen at school; in the 2 years since, she had been unable to sit because of pain in her buttocks. A third case was a 14-year-old girl with widespread pain of unknown origin, many positive findings in a review of systems, and multiple painful points, who has not attended school for 2 years. "Remember, all of these children are suffering," noted Dr. Sherry.

Dr. Sherry’s typical RND patient is female, about 12 years old, and has had symptoms for about a year. These girls tend to have pain in their lower extremities and most say the pain is constant and in multiple sites. The pain often begins after minor trauma, is worse with rest, and increases over time. Patients often have allodynia, but the area of allodynia characteristically has variable borders. Some patients have autonomic signs, such as limbs that are cold, clammy, and cyanotic and dystrophic skin. Lab tests are normal although MRI may show edema.

"Some of these kids tend to have multiple diagnoses of stress fractures," says Dr. Sherry. They have overt signs of autonomic dysfunction so the patients and families do not accept that it is "all in the patient’s head."

Nevertheless psychological stress seems to play a role in at least 80% of children with RND. The most common stresses seen in children with RND involve family and school issues. Dr. Sherry reported there being some common personality features in affected children. For instance, the typical patient is "pseudomature," excels in school and sports, and strives to please people and be a perfectionist. Often the patient and her mother seem overly enmeshed with each other, as manifested by "finishing each other’s sentences" or dressing alike. The fathers are often detached. An odd characteristic is an incongruent affect: "amplified pain tends to make the patient smile," says Dr. Sherry.

To break the cycle of pain, the first thing Dr. Sherry recommends is to halt all medical testing and discontinue medications. Depending on the severity of the problem, he then advocates a specialized strenuous program of exercise. During a typical day, the child may participate in pool activities, physical therapy (animal walks, 90-foot runs, step-ups, mini-trampoline jumping, ball exercises), and occupational therapy (stepping in and out of a bathtub, getting up and down from the floor, window painting, writing). Music therapy provides methods of coping, including music-assisted relaxation techniques; and songwriting allows self-expression. Patients also meet with psychologists for counseling sessions. Art therapy is also used to try to help the children connect to their feelings.

While some patients are able to do this at home, most children need daily outpatient therapy lasting 5 to 6 hours a day. "A few children require hospitalization, especially those who are severely incapacitated, those who have marked pain behaviors such as night time screaming and those who need a behavior-modification program." During this time, most children begin to regain function although pain may initially increase because of all the exercise.

The average child requires 2-4 weeks of this exercise program. Physical therapists also use towel and lotion rubs and massage to desensitize areas that are particularly painful to touch. Patients are expected to exercise at home on weekends. During this time, participants do not attend school. Parents are not allowed in the gyms; they are encouraged to participate in parent counseling groups and maintain their normal routines.

Upon completion of the exercise program, the children return home to restart their normal activities, including return to school. For children who have been absent from school, Dr. Sherry’s staff works with school staff members to reintegrate the child gradually, sometimes beginning by just having the child spend time in the parking lot or school library. Patients are expected to exercise at home for about 45 minutes a day, and counseling is usually recommended. During this time, pain starts to recede. In the last part of the program, children can stop formal home exercise and hopefully function without pain.

Within the first 1-2 weeks, 80% of patients become fully functional and 95% are fully functional within the first month. After 1 month, 75% are free of pain, according to Dr. Sherry.

Preliminary results are available from an ongoing study in which patients were evaluated for pain and function before the start and after completion of the exercise program, as well as at 1-year follow-up. Preliminary data on 20 subjects showed the mean pain score on a visual analog scale (VAS) before the program was 62.7 out of 100; after the program ended the VAS significantly decreased to 33.9 (P less than .01) and after 1 year, the mean VAS was significantly decreased further to 17.3 (P = .02). Similar trends were seen for fine-motor control, manual coordination, and a total motor composite score. Significant improvements were also seen by the end of the exercise program in body coordination and strength and agility (both P less than .01) but scores remained stable once the program was completed.

Do patients relapse? In an earlier study of 49 patients with an amplified pain syndrome who were followed for 5 years, nearly one-third relapsed (Clin. J. Pain 1999;15:218-23). The median time to relapse was 2 months and 79% relapsed within the first 6 months. "The important thing was that most relapses resolved quickly with 50% of patients able to control their relapse at home by themselves," says Dr. Sherry.

"Within a few weeks, we can get most kids fully functional without drugs or invasive procedures. Kids who won’t put a shoe on, kids who can’t walk, kids on crutches, kids who have been in a wheelchair for 2 years. Within a couple of weeks, we get them to be at least weight bearing."

Dr. Sherry reported having no relevant financial disclosures.

NEW YORK – An intensive program that includes physical, occupational, and psychological therapy can help most children suffering from pain amplification syndrome to become fully functional within the first 1-2 weeks of treatment and pain free within the first month, according to Dr. David D. Sherry, who spoke at a meeting sponsored by the New York University. The improvements tend to be durable and relapses resolve quickly, often through self care.

A very painful medical condition, amplified musculoskeletal pain or reflex neurovascular dystrophy (RND) usually affects a limb but can cause pain anywhere on the body. Some children have pain all over and a few have intermittent attacks of pain. "The pain these children experience, however, is much more intense than one would normally expect because the pain signal is amplified," according to Dr. Sherry, chief of the rheumatology section at the Children’s Hospital of Philadelphia.

Dr. Sherry described several of the 1,900 cases he has seen in his practice, among them a 12-year-old girl who had banged her foot during basketball. Her foot was cold and blue 3 days later, she could not wear a sock, and she was on crutches. Another 12-year-old patient had fallen at school; in the 2 years since, she had been unable to sit because of pain in her buttocks. A third case was a 14-year-old girl with widespread pain of unknown origin, many positive findings in a review of systems, and multiple painful points, who has not attended school for 2 years. "Remember, all of these children are suffering," noted Dr. Sherry.

Dr. Sherry’s typical RND patient is female, about 12 years old, and has had symptoms for about a year. These girls tend to have pain in their lower extremities and most say the pain is constant and in multiple sites. The pain often begins after minor trauma, is worse with rest, and increases over time. Patients often have allodynia, but the area of allodynia characteristically has variable borders. Some patients have autonomic signs, such as limbs that are cold, clammy, and cyanotic and dystrophic skin. Lab tests are normal although MRI may show edema.

"Some of these kids tend to have multiple diagnoses of stress fractures," says Dr. Sherry. They have overt signs of autonomic dysfunction so the patients and families do not accept that it is "all in the patient’s head."

Nevertheless psychological stress seems to play a role in at least 80% of children with RND. The most common stresses seen in children with RND involve family and school issues. Dr. Sherry reported there being some common personality features in affected children. For instance, the typical patient is "pseudomature," excels in school and sports, and strives to please people and be a perfectionist. Often the patient and her mother seem overly enmeshed with each other, as manifested by "finishing each other’s sentences" or dressing alike. The fathers are often detached. An odd characteristic is an incongruent affect: "amplified pain tends to make the patient smile," says Dr. Sherry.

To break the cycle of pain, the first thing Dr. Sherry recommends is to halt all medical testing and discontinue medications. Depending on the severity of the problem, he then advocates a specialized strenuous program of exercise. During a typical day, the child may participate in pool activities, physical therapy (animal walks, 90-foot runs, step-ups, mini-trampoline jumping, ball exercises), and occupational therapy (stepping in and out of a bathtub, getting up and down from the floor, window painting, writing). Music therapy provides methods of coping, including music-assisted relaxation techniques; and songwriting allows self-expression. Patients also meet with psychologists for counseling sessions. Art therapy is also used to try to help the children connect to their feelings.

While some patients are able to do this at home, most children need daily outpatient therapy lasting 5 to 6 hours a day. "A few children require hospitalization, especially those who are severely incapacitated, those who have marked pain behaviors such as night time screaming and those who need a behavior-modification program." During this time, most children begin to regain function although pain may initially increase because of all the exercise.

The average child requires 2-4 weeks of this exercise program. Physical therapists also use towel and lotion rubs and massage to desensitize areas that are particularly painful to touch. Patients are expected to exercise at home on weekends. During this time, participants do not attend school. Parents are not allowed in the gyms; they are encouraged to participate in parent counseling groups and maintain their normal routines.

Upon completion of the exercise program, the children return home to restart their normal activities, including return to school. For children who have been absent from school, Dr. Sherry’s staff works with school staff members to reintegrate the child gradually, sometimes beginning by just having the child spend time in the parking lot or school library. Patients are expected to exercise at home for about 45 minutes a day, and counseling is usually recommended. During this time, pain starts to recede. In the last part of the program, children can stop formal home exercise and hopefully function without pain.

Within the first 1-2 weeks, 80% of patients become fully functional and 95% are fully functional within the first month. After 1 month, 75% are free of pain, according to Dr. Sherry.

Preliminary results are available from an ongoing study in which patients were evaluated for pain and function before the start and after completion of the exercise program, as well as at 1-year follow-up. Preliminary data on 20 subjects showed the mean pain score on a visual analog scale (VAS) before the program was 62.7 out of 100; after the program ended the VAS significantly decreased to 33.9 (P less than .01) and after 1 year, the mean VAS was significantly decreased further to 17.3 (P = .02). Similar trends were seen for fine-motor control, manual coordination, and a total motor composite score. Significant improvements were also seen by the end of the exercise program in body coordination and strength and agility (both P less than .01) but scores remained stable once the program was completed.

Do patients relapse? In an earlier study of 49 patients with an amplified pain syndrome who were followed for 5 years, nearly one-third relapsed (Clin. J. Pain 1999;15:218-23). The median time to relapse was 2 months and 79% relapsed within the first 6 months. "The important thing was that most relapses resolved quickly with 50% of patients able to control their relapse at home by themselves," says Dr. Sherry.

"Within a few weeks, we can get most kids fully functional without drugs or invasive procedures. Kids who won’t put a shoe on, kids who can’t walk, kids on crutches, kids who have been in a wheelchair for 2 years. Within a couple of weeks, we get them to be at least weight bearing."

Dr. Sherry reported having no relevant financial disclosures.

NEW YORK – An intensive program that includes physical, occupational, and psychological therapy can help most children suffering from pain amplification syndrome to become fully functional within the first 1-2 weeks of treatment and pain free within the first month, according to Dr. David D. Sherry, who spoke at a meeting sponsored by the New York University. The improvements tend to be durable and relapses resolve quickly, often through self care.

A very painful medical condition, amplified musculoskeletal pain or reflex neurovascular dystrophy (RND) usually affects a limb but can cause pain anywhere on the body. Some children have pain all over and a few have intermittent attacks of pain. "The pain these children experience, however, is much more intense than one would normally expect because the pain signal is amplified," according to Dr. Sherry, chief of the rheumatology section at the Children’s Hospital of Philadelphia.

Dr. Sherry described several of the 1,900 cases he has seen in his practice, among them a 12-year-old girl who had banged her foot during basketball. Her foot was cold and blue 3 days later, she could not wear a sock, and she was on crutches. Another 12-year-old patient had fallen at school; in the 2 years since, she had been unable to sit because of pain in her buttocks. A third case was a 14-year-old girl with widespread pain of unknown origin, many positive findings in a review of systems, and multiple painful points, who has not attended school for 2 years. "Remember, all of these children are suffering," noted Dr. Sherry.

Dr. Sherry’s typical RND patient is female, about 12 years old, and has had symptoms for about a year. These girls tend to have pain in their lower extremities and most say the pain is constant and in multiple sites. The pain often begins after minor trauma, is worse with rest, and increases over time. Patients often have allodynia, but the area of allodynia characteristically has variable borders. Some patients have autonomic signs, such as limbs that are cold, clammy, and cyanotic and dystrophic skin. Lab tests are normal although MRI may show edema.

"Some of these kids tend to have multiple diagnoses of stress fractures," says Dr. Sherry. They have overt signs of autonomic dysfunction so the patients and families do not accept that it is "all in the patient’s head."

Nevertheless psychological stress seems to play a role in at least 80% of children with RND. The most common stresses seen in children with RND involve family and school issues. Dr. Sherry reported there being some common personality features in affected children. For instance, the typical patient is "pseudomature," excels in school and sports, and strives to please people and be a perfectionist. Often the patient and her mother seem overly enmeshed with each other, as manifested by "finishing each other’s sentences" or dressing alike. The fathers are often detached. An odd characteristic is an incongruent affect: "amplified pain tends to make the patient smile," says Dr. Sherry.

To break the cycle of pain, the first thing Dr. Sherry recommends is to halt all medical testing and discontinue medications. Depending on the severity of the problem, he then advocates a specialized strenuous program of exercise. During a typical day, the child may participate in pool activities, physical therapy (animal walks, 90-foot runs, step-ups, mini-trampoline jumping, ball exercises), and occupational therapy (stepping in and out of a bathtub, getting up and down from the floor, window painting, writing). Music therapy provides methods of coping, including music-assisted relaxation techniques; and songwriting allows self-expression. Patients also meet with psychologists for counseling sessions. Art therapy is also used to try to help the children connect to their feelings.

While some patients are able to do this at home, most children need daily outpatient therapy lasting 5 to 6 hours a day. "A few children require hospitalization, especially those who are severely incapacitated, those who have marked pain behaviors such as night time screaming and those who need a behavior-modification program." During this time, most children begin to regain function although pain may initially increase because of all the exercise.

The average child requires 2-4 weeks of this exercise program. Physical therapists also use towel and lotion rubs and massage to desensitize areas that are particularly painful to touch. Patients are expected to exercise at home on weekends. During this time, participants do not attend school. Parents are not allowed in the gyms; they are encouraged to participate in parent counseling groups and maintain their normal routines.

Upon completion of the exercise program, the children return home to restart their normal activities, including return to school. For children who have been absent from school, Dr. Sherry’s staff works with school staff members to reintegrate the child gradually, sometimes beginning by just having the child spend time in the parking lot or school library. Patients are expected to exercise at home for about 45 minutes a day, and counseling is usually recommended. During this time, pain starts to recede. In the last part of the program, children can stop formal home exercise and hopefully function without pain.

Within the first 1-2 weeks, 80% of patients become fully functional and 95% are fully functional within the first month. After 1 month, 75% are free of pain, according to Dr. Sherry.

Preliminary results are available from an ongoing study in which patients were evaluated for pain and function before the start and after completion of the exercise program, as well as at 1-year follow-up. Preliminary data on 20 subjects showed the mean pain score on a visual analog scale (VAS) before the program was 62.7 out of 100; after the program ended the VAS significantly decreased to 33.9 (P less than .01) and after 1 year, the mean VAS was significantly decreased further to 17.3 (P = .02). Similar trends were seen for fine-motor control, manual coordination, and a total motor composite score. Significant improvements were also seen by the end of the exercise program in body coordination and strength and agility (both P less than .01) but scores remained stable once the program was completed.

Do patients relapse? In an earlier study of 49 patients with an amplified pain syndrome who were followed for 5 years, nearly one-third relapsed (Clin. J. Pain 1999;15:218-23). The median time to relapse was 2 months and 79% relapsed within the first 6 months. "The important thing was that most relapses resolved quickly with 50% of patients able to control their relapse at home by themselves," says Dr. Sherry.

"Within a few weeks, we can get most kids fully functional without drugs or invasive procedures. Kids who won’t put a shoe on, kids who can’t walk, kids on crutches, kids who have been in a wheelchair for 2 years. Within a couple of weeks, we get them to be at least weight bearing."

Dr. Sherry reported having no relevant financial disclosures.

NEW YORK – High rates of endometriosis and symptoms indicative of possible future endometriosis have been noted in adolescents and young women based on prevalence data from the United States.

Stacey A. Missmer, Sc.D., reported results from the prospective GUTS (Growing Up Today Study), which includes 15,000 daughters of enrollees of the second Nurses’ Health Study.

GUTS participants were enrolled at 9-15 years of age, and the study was started in 1996 as a long-term prospective investigation of factors that influence weight change, she said at the annual congress of the Endometriosis Foundation of America.

So far, there have been 250 incident cases of endometriosis in GUTS enrollees, and 3,000 others (20%) have reported symptoms indicative of possible future endometriosis, including moderate to severe dysmenorrhea, chronic pelvic pain resistant to analgesics, and lower back pain, according to Dr. Missmer, director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital in Boston and senior endometriosis investigator for the Nurses’ Health Study.

Also at the meeting, Dr. Thomas D’Hooghe, a professor at the Catholic University of Leuven and director of the Leuven (Belgium) University Fertility Center, presented the results of a systematic literature review of 1,014 publications over a 30-year span, with 15 studies found to examine the prevalence of endometriosis in adolescents.

Of 893 girls who presented for laparoscopy with chronic pelvic pain or dysmenorrhea and were resistant to treatment with oral contraceptives or NSAIDS, 62% were diagnosed with endometriosis. In the subpopulation of those with chronic pelvic pain alone, the prevalence of endometriosis was 49%, he reported.

In the studies that evaluated disease severity, 32% (82 of 249) of adolescent patients had moderate to severe endometriosis. Laparoscopic findings included rectal lesions and tubo-ovarian adhesions, extensive disease of the peritoneum, ovaries and surrounding structures, and rectovaginal, bowel and ureteric endometriosis.

Not much data are available on endometriosis in adolescents. A common thread of adult endometriosis patient testimonials during the conference was the dismissal of their severe menstrual pain as "normal" by family members and health professionals. Many said that they were not diagnosed until 12 years or more after the onset of symptoms.

Dr. D’Hooghe additionally reported unpublished findings from a survey. Among 12-year-olds (n = 792) who completed a semistructured questionnaire, 363 had achieved menarche and 42% of them reported painful menstruation that correlated with duration of menstrual flow and the amount of blood loss. Among girls with painful menstruation, 41% said that it had a negative toll on social activities. Among girls without menstrual-related pain, 14% said menstruation impaired their social activities (P <.001).

Among the 13- to 16-year-olds (n = 172), 40% reported menstrual pain and 17% reported severe menstrual pain. In the 17- to 21-year-olds (n = 1,028), 52% reported menstrual pain and 16% reported severe menstrual pain. Over 40% in each age group used hormonal contraception for analgesia.

Menstrually related nongynecologic complaints included lower back pain reported by 26% of the 13- to 16-year-olds and by 38% of the 17- to 21-year-olds; urological symptoms reported by 26% and 23%, respectively; and gastrointestinal problems reported by 14% and 24% respectively.

"This group of girls who not only present with typical gynecological problems but also with lower back pain, urological symptoms, and gastrointestinal problems are the girls we want to see in our clinics for early diagnosis and treatment," said Dr. D’Hooghe.

Known factors that are linked to the risk of endometriosis include early dysmenorrhea, family history of endometriosis, high frequency and long duration of oral contraceptive use for severe dysmenorrhea, and frequent absences from school during menstruation. Reaching menarche after the age of 14 years is associated with a decreased risk of endometriosis, he said.

Dr. Missmer and Dr. D’Hooghe had no relevant financial disclosures.

NEW YORK – High rates of endometriosis and symptoms indicative of possible future endometriosis have been noted in adolescents and young women based on prevalence data from the United States.

Stacey A. Missmer, Sc.D., reported results from the prospective GUTS (Growing Up Today Study), which includes 15,000 daughters of enrollees of the second Nurses’ Health Study.

GUTS participants were enrolled at 9-15 years of age, and the study was started in 1996 as a long-term prospective investigation of factors that influence weight change, she said at the annual congress of the Endometriosis Foundation of America.

So far, there have been 250 incident cases of endometriosis in GUTS enrollees, and 3,000 others (20%) have reported symptoms indicative of possible future endometriosis, including moderate to severe dysmenorrhea, chronic pelvic pain resistant to analgesics, and lower back pain, according to Dr. Missmer, director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital in Boston and senior endometriosis investigator for the Nurses’ Health Study.

Also at the meeting, Dr. Thomas D’Hooghe, a professor at the Catholic University of Leuven and director of the Leuven (Belgium) University Fertility Center, presented the results of a systematic literature review of 1,014 publications over a 30-year span, with 15 studies found to examine the prevalence of endometriosis in adolescents.

Of 893 girls who presented for laparoscopy with chronic pelvic pain or dysmenorrhea and were resistant to treatment with oral contraceptives or NSAIDS, 62% were diagnosed with endometriosis. In the subpopulation of those with chronic pelvic pain alone, the prevalence of endometriosis was 49%, he reported.

In the studies that evaluated disease severity, 32% (82 of 249) of adolescent patients had moderate to severe endometriosis. Laparoscopic findings included rectal lesions and tubo-ovarian adhesions, extensive disease of the peritoneum, ovaries and surrounding structures, and rectovaginal, bowel and ureteric endometriosis.

Not much data are available on endometriosis in adolescents. A common thread of adult endometriosis patient testimonials during the conference was the dismissal of their severe menstrual pain as "normal" by family members and health professionals. Many said that they were not diagnosed until 12 years or more after the onset of symptoms.

Dr. D’Hooghe additionally reported unpublished findings from a survey. Among 12-year-olds (n = 792) who completed a semistructured questionnaire, 363 had achieved menarche and 42% of them reported painful menstruation that correlated with duration of menstrual flow and the amount of blood loss. Among girls with painful menstruation, 41% said that it had a negative toll on social activities. Among girls without menstrual-related pain, 14% said menstruation impaired their social activities (P <.001).

Among the 13- to 16-year-olds (n = 172), 40% reported menstrual pain and 17% reported severe menstrual pain. In the 17- to 21-year-olds (n = 1,028), 52% reported menstrual pain and 16% reported severe menstrual pain. Over 40% in each age group used hormonal contraception for analgesia.

Menstrually related nongynecologic complaints included lower back pain reported by 26% of the 13- to 16-year-olds and by 38% of the 17- to 21-year-olds; urological symptoms reported by 26% and 23%, respectively; and gastrointestinal problems reported by 14% and 24% respectively.

"This group of girls who not only present with typical gynecological problems but also with lower back pain, urological symptoms, and gastrointestinal problems are the girls we want to see in our clinics for early diagnosis and treatment," said Dr. D’Hooghe.

Known factors that are linked to the risk of endometriosis include early dysmenorrhea, family history of endometriosis, high frequency and long duration of oral contraceptive use for severe dysmenorrhea, and frequent absences from school during menstruation. Reaching menarche after the age of 14 years is associated with a decreased risk of endometriosis, he said.

Dr. Missmer and Dr. D’Hooghe had no relevant financial disclosures.

NEW YORK – High rates of endometriosis and symptoms indicative of possible future endometriosis have been noted in adolescents and young women based on prevalence data from the United States.

Stacey A. Missmer, Sc.D., reported results from the prospective GUTS (Growing Up Today Study), which includes 15,000 daughters of enrollees of the second Nurses’ Health Study.

GUTS participants were enrolled at 9-15 years of age, and the study was started in 1996 as a long-term prospective investigation of factors that influence weight change, she said at the annual congress of the Endometriosis Foundation of America.

So far, there have been 250 incident cases of endometriosis in GUTS enrollees, and 3,000 others (20%) have reported symptoms indicative of possible future endometriosis, including moderate to severe dysmenorrhea, chronic pelvic pain resistant to analgesics, and lower back pain, according to Dr. Missmer, director of epidemiologic research in reproductive medicine at Brigham and Women’s Hospital in Boston and senior endometriosis investigator for the Nurses’ Health Study.

Also at the meeting, Dr. Thomas D’Hooghe, a professor at the Catholic University of Leuven and director of the Leuven (Belgium) University Fertility Center, presented the results of a systematic literature review of 1,014 publications over a 30-year span, with 15 studies found to examine the prevalence of endometriosis in adolescents.

Of 893 girls who presented for laparoscopy with chronic pelvic pain or dysmenorrhea and were resistant to treatment with oral contraceptives or NSAIDS, 62% were diagnosed with endometriosis. In the subpopulation of those with chronic pelvic pain alone, the prevalence of endometriosis was 49%, he reported.

In the studies that evaluated disease severity, 32% (82 of 249) of adolescent patients had moderate to severe endometriosis. Laparoscopic findings included rectal lesions and tubo-ovarian adhesions, extensive disease of the peritoneum, ovaries and surrounding structures, and rectovaginal, bowel and ureteric endometriosis.

Not much data are available on endometriosis in adolescents. A common thread of adult endometriosis patient testimonials during the conference was the dismissal of their severe menstrual pain as "normal" by family members and health professionals. Many said that they were not diagnosed until 12 years or more after the onset of symptoms.

Dr. D’Hooghe additionally reported unpublished findings from a survey. Among 12-year-olds (n = 792) who completed a semistructured questionnaire, 363 had achieved menarche and 42% of them reported painful menstruation that correlated with duration of menstrual flow and the amount of blood loss. Among girls with painful menstruation, 41% said that it had a negative toll on social activities. Among girls without menstrual-related pain, 14% said menstruation impaired their social activities (P <.001).

Among the 13- to 16-year-olds (n = 172), 40% reported menstrual pain and 17% reported severe menstrual pain. In the 17- to 21-year-olds (n = 1,028), 52% reported menstrual pain and 16% reported severe menstrual pain. Over 40% in each age group used hormonal contraception for analgesia.

Menstrually related nongynecologic complaints included lower back pain reported by 26% of the 13- to 16-year-olds and by 38% of the 17- to 21-year-olds; urological symptoms reported by 26% and 23%, respectively; and gastrointestinal problems reported by 14% and 24% respectively.

"This group of girls who not only present with typical gynecological problems but also with lower back pain, urological symptoms, and gastrointestinal problems are the girls we want to see in our clinics for early diagnosis and treatment," said Dr. D’Hooghe.

Known factors that are linked to the risk of endometriosis include early dysmenorrhea, family history of endometriosis, high frequency and long duration of oral contraceptive use for severe dysmenorrhea, and frequent absences from school during menstruation. Reaching menarche after the age of 14 years is associated with a decreased risk of endometriosis, he said.

Dr. Missmer and Dr. D’Hooghe had no relevant financial disclosures.