Patrice Wendling

CHICAGO — Few physicians would be fooled nowadays by gadolinium-induced nephrogenic systemic fibrosis, but there are other diseases that can masquerade as scleroderma.

The precise diagnosis of sclerodermalike illnesses is important because even though many of them are called scleroderma, they are different from systemic sclerosis in their treatments and outcomes, Dr. Virginia Steen said at a symposium sponsored by the American College of Rheumatology.

The diagnosis is most often based on the distribution and clinical characteristics of skin findings, as biopsies don't always differentiate types of scleroderma. She recommended watching for the following four conditions:

▸ Lipodermatosclerosis is one condition that physicians often fail to think of as a scleroderma mimic. Also known as hypodermatitis sclerodermaformis, it refers to localized chronic inflammation and fibrosis of the skin and subcutaneous tissues of the lower leg. In the acute stage, the leg is inflamed and warm, the skin is very tight, and cellulitis may be present. The ankle and toes are not involved.

In its chronic stage, there is induration, contraction of the skin and subcutaneous tissues, and irregular depressions that can look almost identical to lower-leg scleroderma, she said.

The leg eventually resembles an inverted champagne bottle, in which the upper half remains edematous and has a much greater circumference than does the lower sclerotic portion.

Lipodermatosclerosis is sign of severe end-stage venous insufficiency, and should be differentiated from scleroderma, cellulitis, superficial thrombophlebitis, and erythema nodosum. The diagnosis is made from clinical observation, but direct immunofluorescence of early and late lesions has been used to show dermal pericapillary fibrin deposits.

If left untreated, lipodermatosclerosis can progress to ulceration, atrophy blanche, or shortening of the Achilles tendon. Treatment involves weight loss, controlling the underlying disease, and emphasis on support stockings that may need to be specially made, said Dr. Steen, who is professor of medicine and director of the rheumatology fellowship program at Georgetown University in Washington.

Topical steroids are useful if the skin is inflamed, and antibiotics are recommended for cellulitis.

▸ Scleredema tends to target the upper body without affecting the lower extremities. The skin on the neck and face thicken and harden; severely affected patients are unable to wrinkle their foreheads or open their mouths. In most patients, the shawl sign is present, with skin involvement over the chest and arms, she said.

Pathologic features include swollen collagen with clear spaces and accumulation of hyaluronic acid and glycosaminoglycans. Although scleredema is commonly associated with diabetes, it can also occur after a viral illness.

▸ Eosinophilic fasciitis is a rare disorder characterized by symmetrical and painful inflammation and swelling of the extremities, leading to induration and the characteristic peau d'orange configuration. The palms may be involved, but typically the fingers and toes are spared. Contractures demonstrating the groove sign commonly evolve as a result of induration.

Eosinophilic fasciitis is slightly more common in middle-aged men, but can occur in women and children. It was initially distinguished from systemic sclerosis by the absence of Raynaud's phenomenon, autoantibodies, and visceral involvement, and—unlike systemic sclerosis—it responds to corticosteroids, Dr. Steen said.

Histologically, there are marked eosinophilia and inflammatory infiltrates in the fascia. The extent of the histologic changes depends on the stage of the disease, and thus is not a consistent component of the disease. Aside from marked peripheral eosinophilia, other laboratory features to watch for include an increased erythrocyte sedimentation rate, increased gamma globulin, and an increased aldolase, with a normal creatinine phosphokinase.

Aggressive physical therapy is a key component of treatment, because this and most scleroderma mimics discussed here can cause joint contractures. In eosinophilic fasciitis, low- to moderate-dose prednisone (20–30 mg)—and, if needed, methotrexate as a steroid-sparing agent—can be given, Dr. Steen said.

▸ Diabetic cheiroarthropathy is a syndrome of limited joint mobility in the hands. It is characterized by thickened, tight, waxy hands with sclerosis of the palmar tendon sheaths that noticeably restricts mobility in the proximal interphalangeal joints and metacarpophalangeal joints.

The “prayer sign,” in which the patient will be unable to fully oppose the palmar surfaces of the digits, is a clue to this diagnosis when it is present in a patient with diabetes, said Dr. Steen, who disclosed no relevant conflicts of interest.

The sclerotic plaque on this patient's lower leg is lipodermatosclerosis. Courtesy Dr. Kenneth E. Greer

CHICAGO — Few physicians would be fooled nowadays by gadolinium-induced nephrogenic systemic fibrosis, but there are other diseases that can masquerade as scleroderma.

The precise diagnosis of sclerodermalike illnesses is important because even though many of them are called scleroderma, they are different from systemic sclerosis in their treatments and outcomes, Dr. Virginia Steen said at a symposium sponsored by the American College of Rheumatology.

The diagnosis is most often based on the distribution and clinical characteristics of skin findings, as biopsies don't always differentiate types of scleroderma. She recommended watching for the following four conditions:

▸ Lipodermatosclerosis is one condition that physicians often fail to think of as a scleroderma mimic. Also known as hypodermatitis sclerodermaformis, it refers to localized chronic inflammation and fibrosis of the skin and subcutaneous tissues of the lower leg. In the acute stage, the leg is inflamed and warm, the skin is very tight, and cellulitis may be present. The ankle and toes are not involved.

In its chronic stage, there is induration, contraction of the skin and subcutaneous tissues, and irregular depressions that can look almost identical to lower-leg scleroderma, she said.

The leg eventually resembles an inverted champagne bottle, in which the upper half remains edematous and has a much greater circumference than does the lower sclerotic portion.

Lipodermatosclerosis is sign of severe end-stage venous insufficiency, and should be differentiated from scleroderma, cellulitis, superficial thrombophlebitis, and erythema nodosum. The diagnosis is made from clinical observation, but direct immunofluorescence of early and late lesions has been used to show dermal pericapillary fibrin deposits.

If left untreated, lipodermatosclerosis can progress to ulceration, atrophy blanche, or shortening of the Achilles tendon. Treatment involves weight loss, controlling the underlying disease, and emphasis on support stockings that may need to be specially made, said Dr. Steen, who is professor of medicine and director of the rheumatology fellowship program at Georgetown University in Washington.

Topical steroids are useful if the skin is inflamed, and antibiotics are recommended for cellulitis.

▸ Scleredema tends to target the upper body without affecting the lower extremities. The skin on the neck and face thicken and harden; severely affected patients are unable to wrinkle their foreheads or open their mouths. In most patients, the shawl sign is present, with skin involvement over the chest and arms, she said.

Pathologic features include swollen collagen with clear spaces and accumulation of hyaluronic acid and glycosaminoglycans. Although scleredema is commonly associated with diabetes, it can also occur after a viral illness.

▸ Eosinophilic fasciitis is a rare disorder characterized by symmetrical and painful inflammation and swelling of the extremities, leading to induration and the characteristic peau d'orange configuration. The palms may be involved, but typically the fingers and toes are spared. Contractures demonstrating the groove sign commonly evolve as a result of induration.

Eosinophilic fasciitis is slightly more common in middle-aged men, but can occur in women and children. It was initially distinguished from systemic sclerosis by the absence of Raynaud's phenomenon, autoantibodies, and visceral involvement, and—unlike systemic sclerosis—it responds to corticosteroids, Dr. Steen said.

Histologically, there are marked eosinophilia and inflammatory infiltrates in the fascia. The extent of the histologic changes depends on the stage of the disease, and thus is not a consistent component of the disease. Aside from marked peripheral eosinophilia, other laboratory features to watch for include an increased erythrocyte sedimentation rate, increased gamma globulin, and an increased aldolase, with a normal creatinine phosphokinase.

Aggressive physical therapy is a key component of treatment, because this and most scleroderma mimics discussed here can cause joint contractures. In eosinophilic fasciitis, low- to moderate-dose prednisone (20–30 mg)—and, if needed, methotrexate as a steroid-sparing agent—can be given, Dr. Steen said.

▸ Diabetic cheiroarthropathy is a syndrome of limited joint mobility in the hands. It is characterized by thickened, tight, waxy hands with sclerosis of the palmar tendon sheaths that noticeably restricts mobility in the proximal interphalangeal joints and metacarpophalangeal joints.

The “prayer sign,” in which the patient will be unable to fully oppose the palmar surfaces of the digits, is a clue to this diagnosis when it is present in a patient with diabetes, said Dr. Steen, who disclosed no relevant conflicts of interest.

The sclerotic plaque on this patient's lower leg is lipodermatosclerosis. Courtesy Dr. Kenneth E. Greer

CHICAGO — Few physicians would be fooled nowadays by gadolinium-induced nephrogenic systemic fibrosis, but there are other diseases that can masquerade as scleroderma.

The precise diagnosis of sclerodermalike illnesses is important because even though many of them are called scleroderma, they are different from systemic sclerosis in their treatments and outcomes, Dr. Virginia Steen said at a symposium sponsored by the American College of Rheumatology.

The diagnosis is most often based on the distribution and clinical characteristics of skin findings, as biopsies don't always differentiate types of scleroderma. She recommended watching for the following four conditions:

▸ Lipodermatosclerosis is one condition that physicians often fail to think of as a scleroderma mimic. Also known as hypodermatitis sclerodermaformis, it refers to localized chronic inflammation and fibrosis of the skin and subcutaneous tissues of the lower leg. In the acute stage, the leg is inflamed and warm, the skin is very tight, and cellulitis may be present. The ankle and toes are not involved.

In its chronic stage, there is induration, contraction of the skin and subcutaneous tissues, and irregular depressions that can look almost identical to lower-leg scleroderma, she said.

The leg eventually resembles an inverted champagne bottle, in which the upper half remains edematous and has a much greater circumference than does the lower sclerotic portion.

Lipodermatosclerosis is sign of severe end-stage venous insufficiency, and should be differentiated from scleroderma, cellulitis, superficial thrombophlebitis, and erythema nodosum. The diagnosis is made from clinical observation, but direct immunofluorescence of early and late lesions has been used to show dermal pericapillary fibrin deposits.

If left untreated, lipodermatosclerosis can progress to ulceration, atrophy blanche, or shortening of the Achilles tendon. Treatment involves weight loss, controlling the underlying disease, and emphasis on support stockings that may need to be specially made, said Dr. Steen, who is professor of medicine and director of the rheumatology fellowship program at Georgetown University in Washington.

Topical steroids are useful if the skin is inflamed, and antibiotics are recommended for cellulitis.

▸ Scleredema tends to target the upper body without affecting the lower extremities. The skin on the neck and face thicken and harden; severely affected patients are unable to wrinkle their foreheads or open their mouths. In most patients, the shawl sign is present, with skin involvement over the chest and arms, she said.

Pathologic features include swollen collagen with clear spaces and accumulation of hyaluronic acid and glycosaminoglycans. Although scleredema is commonly associated with diabetes, it can also occur after a viral illness.

▸ Eosinophilic fasciitis is a rare disorder characterized by symmetrical and painful inflammation and swelling of the extremities, leading to induration and the characteristic peau d'orange configuration. The palms may be involved, but typically the fingers and toes are spared. Contractures demonstrating the groove sign commonly evolve as a result of induration.

Eosinophilic fasciitis is slightly more common in middle-aged men, but can occur in women and children. It was initially distinguished from systemic sclerosis by the absence of Raynaud's phenomenon, autoantibodies, and visceral involvement, and—unlike systemic sclerosis—it responds to corticosteroids, Dr. Steen said.

Histologically, there are marked eosinophilia and inflammatory infiltrates in the fascia. The extent of the histologic changes depends on the stage of the disease, and thus is not a consistent component of the disease. Aside from marked peripheral eosinophilia, other laboratory features to watch for include an increased erythrocyte sedimentation rate, increased gamma globulin, and an increased aldolase, with a normal creatinine phosphokinase.

Aggressive physical therapy is a key component of treatment, because this and most scleroderma mimics discussed here can cause joint contractures. In eosinophilic fasciitis, low- to moderate-dose prednisone (20–30 mg)—and, if needed, methotrexate as a steroid-sparing agent—can be given, Dr. Steen said.

▸ Diabetic cheiroarthropathy is a syndrome of limited joint mobility in the hands. It is characterized by thickened, tight, waxy hands with sclerosis of the palmar tendon sheaths that noticeably restricts mobility in the proximal interphalangeal joints and metacarpophalangeal joints.

The “prayer sign,” in which the patient will be unable to fully oppose the palmar surfaces of the digits, is a clue to this diagnosis when it is present in a patient with diabetes, said Dr. Steen, who disclosed no relevant conflicts of interest.

The sclerotic plaque on this patient's lower leg is lipodermatosclerosis. Courtesy Dr. Kenneth E. Greer

CHICAGO — Trivalent inactivated influenza vaccine may not elicit a clinically adequate antibody response in elderly adults, pilot data suggest.

Based on blood assays taken before and 4 weeks after administration of the Fluarix 2007/2008 formula, 88% of 71 community-dwelling older adults (mean age 85 years) failed to mount a fourfold antibody response to any of the three virus strains present in the trivalent influenza vaccine (TIV).

Only two patients had a fourfold antibody response to both influenza A types, H1N1 and H3N2, and none had such a response to all three strains—H1NI, H3N2, and influenza B, Dr. Sean X. Leng said at the annual meeting of the American Geriatrics Society. A fourfold or higher vaccine antibody titer increase, also called positive seroconversion, is the criterion for a clinically adequate antibody response.

In contrast, he noted that the vaccine insert reports that 444 (60%) of 745 persons, aged 18–64 years, had a fourfold antibody response to the H1N1 strain, 461 (62%) had such a response to H3N2, and 575 (77%) did so to the influenza B strain.

“Obviously this is pilot data, but [it does] point out the importance of the need for comprehensive evaluation of this vaccine in older and frail populations,” commented Dr. Leng, of the division of geriatric medicine and gerontology at Johns Hopkins University in Baltimore.

The audience questioned whether immunity would be a more accurate measure of vaccine protection than antibody response in the elderly since they are more likely than the young to have been vaccinated before and thus would have higher baseline antibody levels.

Of note, researchers at Stanford (Calif.) University recently reported that even the type of vaccine—TIV or live attenuated influenza vaccine—received in prior years affects both serum antibody and B-cell responses to subsequent vaccination (PLoS ONE 2008;8:e2975).

Most patients involved in the current study had high baseline titer levels, which would make it more difficult to achieve positive seroconversion, Dr. Leng acknowledged.

Patients had received flu vaccine for an average of 7 years prior to study entry, although this was based on self-report and subject to memory bias.

Still, 25 (3.4%) of the participants reported having signs and symptoms of flulike illness during the 2007–2008 flu season, although laboratory confirmation of a diagnosis of influenza was not performed.

There were no reported influenza-related deaths.

Influenza is the fourth-leading cause of death in older Americans, with the elderly bearing more than 90% of influenza-related mortality.

Dr. Leng noted that those aged 75 years and older make up a small percentage of vaccine trial cohorts, despite being the fastest-growing segment of the population. In one vaccine trial, only 11% of patients were at least 75 years old (JAMA 1994;272:1661–5).

The one-size-fits-all approach to influenza vaccine needs to be reexamined, as is being done with cancer screening in elderly and other high-risk groups, he suggested.

Patients in the study ranged in age from 72 to 95 years, 79% were women, and 93% were white. The average number of diagnoses was 3.7; these included hypertension (67%), osteoarthritis (45%), and dyslipidemia (38%).

Dr. Leng and his associates reported no conflicts of interest.

The study was sponsored by the National Institute on Aging and the American Federation for Aging Research.

CHICAGO — Trivalent inactivated influenza vaccine may not elicit a clinically adequate antibody response in elderly adults, pilot data suggest.

Based on blood assays taken before and 4 weeks after administration of the Fluarix 2007/2008 formula, 88% of 71 community-dwelling older adults (mean age 85 years) failed to mount a fourfold antibody response to any of the three virus strains present in the trivalent influenza vaccine (TIV).

Only two patients had a fourfold antibody response to both influenza A types, H1N1 and H3N2, and none had such a response to all three strains—H1NI, H3N2, and influenza B, Dr. Sean X. Leng said at the annual meeting of the American Geriatrics Society. A fourfold or higher vaccine antibody titer increase, also called positive seroconversion, is the criterion for a clinically adequate antibody response.

In contrast, he noted that the vaccine insert reports that 444 (60%) of 745 persons, aged 18–64 years, had a fourfold antibody response to the H1N1 strain, 461 (62%) had such a response to H3N2, and 575 (77%) did so to the influenza B strain.

“Obviously this is pilot data, but [it does] point out the importance of the need for comprehensive evaluation of this vaccine in older and frail populations,” commented Dr. Leng, of the division of geriatric medicine and gerontology at Johns Hopkins University in Baltimore.

The audience questioned whether immunity would be a more accurate measure of vaccine protection than antibody response in the elderly since they are more likely than the young to have been vaccinated before and thus would have higher baseline antibody levels.

Of note, researchers at Stanford (Calif.) University recently reported that even the type of vaccine—TIV or live attenuated influenza vaccine—received in prior years affects both serum antibody and B-cell responses to subsequent vaccination (PLoS ONE 2008;8:e2975).

Most patients involved in the current study had high baseline titer levels, which would make it more difficult to achieve positive seroconversion, Dr. Leng acknowledged.

Patients had received flu vaccine for an average of 7 years prior to study entry, although this was based on self-report and subject to memory bias.

Still, 25 (3.4%) of the participants reported having signs and symptoms of flulike illness during the 2007–2008 flu season, although laboratory confirmation of a diagnosis of influenza was not performed.

There were no reported influenza-related deaths.

Influenza is the fourth-leading cause of death in older Americans, with the elderly bearing more than 90% of influenza-related mortality.

Dr. Leng noted that those aged 75 years and older make up a small percentage of vaccine trial cohorts, despite being the fastest-growing segment of the population. In one vaccine trial, only 11% of patients were at least 75 years old (JAMA 1994;272:1661–5).

The one-size-fits-all approach to influenza vaccine needs to be reexamined, as is being done with cancer screening in elderly and other high-risk groups, he suggested.

Patients in the study ranged in age from 72 to 95 years, 79% were women, and 93% were white. The average number of diagnoses was 3.7; these included hypertension (67%), osteoarthritis (45%), and dyslipidemia (38%).

Dr. Leng and his associates reported no conflicts of interest.

The study was sponsored by the National Institute on Aging and the American Federation for Aging Research.

CHICAGO — Trivalent inactivated influenza vaccine may not elicit a clinically adequate antibody response in elderly adults, pilot data suggest.

Based on blood assays taken before and 4 weeks after administration of the Fluarix 2007/2008 formula, 88% of 71 community-dwelling older adults (mean age 85 years) failed to mount a fourfold antibody response to any of the three virus strains present in the trivalent influenza vaccine (TIV).

Only two patients had a fourfold antibody response to both influenza A types, H1N1 and H3N2, and none had such a response to all three strains—H1NI, H3N2, and influenza B, Dr. Sean X. Leng said at the annual meeting of the American Geriatrics Society. A fourfold or higher vaccine antibody titer increase, also called positive seroconversion, is the criterion for a clinically adequate antibody response.

In contrast, he noted that the vaccine insert reports that 444 (60%) of 745 persons, aged 18–64 years, had a fourfold antibody response to the H1N1 strain, 461 (62%) had such a response to H3N2, and 575 (77%) did so to the influenza B strain.

“Obviously this is pilot data, but [it does] point out the importance of the need for comprehensive evaluation of this vaccine in older and frail populations,” commented Dr. Leng, of the division of geriatric medicine and gerontology at Johns Hopkins University in Baltimore.

The audience questioned whether immunity would be a more accurate measure of vaccine protection than antibody response in the elderly since they are more likely than the young to have been vaccinated before and thus would have higher baseline antibody levels.

Of note, researchers at Stanford (Calif.) University recently reported that even the type of vaccine—TIV or live attenuated influenza vaccine—received in prior years affects both serum antibody and B-cell responses to subsequent vaccination (PLoS ONE 2008;8:e2975).

Most patients involved in the current study had high baseline titer levels, which would make it more difficult to achieve positive seroconversion, Dr. Leng acknowledged.

Patients had received flu vaccine for an average of 7 years prior to study entry, although this was based on self-report and subject to memory bias.

Still, 25 (3.4%) of the participants reported having signs and symptoms of flulike illness during the 2007–2008 flu season, although laboratory confirmation of a diagnosis of influenza was not performed.

There were no reported influenza-related deaths.

Influenza is the fourth-leading cause of death in older Americans, with the elderly bearing more than 90% of influenza-related mortality.

Dr. Leng noted that those aged 75 years and older make up a small percentage of vaccine trial cohorts, despite being the fastest-growing segment of the population. In one vaccine trial, only 11% of patients were at least 75 years old (JAMA 1994;272:1661–5).

The one-size-fits-all approach to influenza vaccine needs to be reexamined, as is being done with cancer screening in elderly and other high-risk groups, he suggested.

Patients in the study ranged in age from 72 to 95 years, 79% were women, and 93% were white. The average number of diagnoses was 3.7; these included hypertension (67%), osteoarthritis (45%), and dyslipidemia (38%).

Dr. Leng and his associates reported no conflicts of interest.

The study was sponsored by the National Institute on Aging and the American Federation for Aging Research.

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs (such as aspirin or ibuprofen) or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Conventional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths attributed yearly to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the VA Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037-45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a conventional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the NSAID alone (Curr. Opin. Rheumatol. 2008;20:239-45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

He noted the guideline's caution concerning methadone, and recommended that only clinicians who are well versed in its use and risks initiate and titrate the drug. “That doesn't mean you don't do it,” said Dr. Fine, “but hook yourself up to someone who has a lot of experience in this when you believe this drug is indicated, if you don't already have the experience.”

Methadone-related deaths during pain treatment have risen up to eightfold in the past few years. This is largely because methadone is attractive as a relatively inexpensive drug, but it has an unpredictable and long half-life. That the drug stays active is a blessing, but that quality is also a problem because it accumulates in the body, Dr. Fine said.

Earlier this year, the American Pain Society and the American Academy of Pain Medicine released clinical guidance on the management of opioid therapy for chronic noncancer pain (J. Pain 2009;10:113-30). Like the AGS guidelines, that document stressed the need for clinicians to regularly assess patients for pain intensity, functional status, side effects, and safe and responsible use.

The updated AGS guideline gives new references and discussions on the use and limitations of newer adjuvant, topical, and other drugs for recalcitrant pain.

“Persistent pain isn't a normal part of aging and should not be ignored,” Dr. Cheryl Phillips, AGS president, said in a statement. “As seniors become susceptible to more complex health ailments, the need for a clear and precise pain management plan is key.”

The AGS published its first pain guideline in 1998. To arrive at the 2009 recommendations, a panel of experts conducted a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The panel focused on pharmacotherapy because it is the most common strategy used for pain management among elderly people, as well as the area of greatest risk, said Dr. Bruce Ferrell of the University of California, Los Angeles, who chaired the panel. The 2009 update is to be published in an upcoming issue of the Journal of the American Geriatrics Society.

Dr. Katz disclosed that he has served as a paid consultant in the last 12 months for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine said he is a paid consultant or speaker for numerous pharmaceutical companies and has commercial interests in Johnson & Johnson and Cephalon Inc. Dr. Ferrell disclosed no relevant conflict of interest.

Members of the American Geriatric Society panel on the pharmacologic management of persistent pain in older persons include (from left to right) Dr. Bruce Ferrell, Dr. Perry Fine, Dr. James Katz, Dr. F. Michael Gloth III, and Lori Reisner, Pharm.D., shown discussing the release of the guidelines at the AGS annual meeting. Patrice Wendling/Elsevier Global Medical News

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs (such as aspirin or ibuprofen) or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Conventional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths attributed yearly to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the VA Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037-45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a conventional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the NSAID alone (Curr. Opin. Rheumatol. 2008;20:239-45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

He noted the guideline's caution concerning methadone, and recommended that only clinicians who are well versed in its use and risks initiate and titrate the drug. “That doesn't mean you don't do it,” said Dr. Fine, “but hook yourself up to someone who has a lot of experience in this when you believe this drug is indicated, if you don't already have the experience.”

Methadone-related deaths during pain treatment have risen up to eightfold in the past few years. This is largely because methadone is attractive as a relatively inexpensive drug, but it has an unpredictable and long half-life. That the drug stays active is a blessing, but that quality is also a problem because it accumulates in the body, Dr. Fine said.

Earlier this year, the American Pain Society and the American Academy of Pain Medicine released clinical guidance on the management of opioid therapy for chronic noncancer pain (J. Pain 2009;10:113-30). Like the AGS guidelines, that document stressed the need for clinicians to regularly assess patients for pain intensity, functional status, side effects, and safe and responsible use.

The updated AGS guideline gives new references and discussions on the use and limitations of newer adjuvant, topical, and other drugs for recalcitrant pain.

“Persistent pain isn't a normal part of aging and should not be ignored,” Dr. Cheryl Phillips, AGS president, said in a statement. “As seniors become susceptible to more complex health ailments, the need for a clear and precise pain management plan is key.”

The AGS published its first pain guideline in 1998. To arrive at the 2009 recommendations, a panel of experts conducted a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The panel focused on pharmacotherapy because it is the most common strategy used for pain management among elderly people, as well as the area of greatest risk, said Dr. Bruce Ferrell of the University of California, Los Angeles, who chaired the panel. The 2009 update is to be published in an upcoming issue of the Journal of the American Geriatrics Society.

Dr. Katz disclosed that he has served as a paid consultant in the last 12 months for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine said he is a paid consultant or speaker for numerous pharmaceutical companies and has commercial interests in Johnson & Johnson and Cephalon Inc. Dr. Ferrell disclosed no relevant conflict of interest.

Members of the American Geriatric Society panel on the pharmacologic management of persistent pain in older persons include (from left to right) Dr. Bruce Ferrell, Dr. Perry Fine, Dr. James Katz, Dr. F. Michael Gloth III, and Lori Reisner, Pharm.D., shown discussing the release of the guidelines at the AGS annual meeting. Patrice Wendling/Elsevier Global Medical News

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs (such as aspirin or ibuprofen) or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Conventional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths attributed yearly to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the VA Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037-45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a conventional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the NSAID alone (Curr. Opin. Rheumatol. 2008;20:239-45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

He noted the guideline's caution concerning methadone, and recommended that only clinicians who are well versed in its use and risks initiate and titrate the drug. “That doesn't mean you don't do it,” said Dr. Fine, “but hook yourself up to someone who has a lot of experience in this when you believe this drug is indicated, if you don't already have the experience.”

Methadone-related deaths during pain treatment have risen up to eightfold in the past few years. This is largely because methadone is attractive as a relatively inexpensive drug, but it has an unpredictable and long half-life. That the drug stays active is a blessing, but that quality is also a problem because it accumulates in the body, Dr. Fine said.

Earlier this year, the American Pain Society and the American Academy of Pain Medicine released clinical guidance on the management of opioid therapy for chronic noncancer pain (J. Pain 2009;10:113-30). Like the AGS guidelines, that document stressed the need for clinicians to regularly assess patients for pain intensity, functional status, side effects, and safe and responsible use.

The updated AGS guideline gives new references and discussions on the use and limitations of newer adjuvant, topical, and other drugs for recalcitrant pain.

“Persistent pain isn't a normal part of aging and should not be ignored,” Dr. Cheryl Phillips, AGS president, said in a statement. “As seniors become susceptible to more complex health ailments, the need for a clear and precise pain management plan is key.”

The AGS published its first pain guideline in 1998. To arrive at the 2009 recommendations, a panel of experts conducted a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The panel focused on pharmacotherapy because it is the most common strategy used for pain management among elderly people, as well as the area of greatest risk, said Dr. Bruce Ferrell of the University of California, Los Angeles, who chaired the panel. The 2009 update is to be published in an upcoming issue of the Journal of the American Geriatrics Society.

Dr. Katz disclosed that he has served as a paid consultant in the last 12 months for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine said he is a paid consultant or speaker for numerous pharmaceutical companies and has commercial interests in Johnson & Johnson and Cephalon Inc. Dr. Ferrell disclosed no relevant conflict of interest.

Members of the American Geriatric Society panel on the pharmacologic management of persistent pain in older persons include (from left to right) Dr. Bruce Ferrell, Dr. Perry Fine, Dr. James Katz, Dr. F. Michael Gloth III, and Lori Reisner, Pharm.D., shown discussing the release of the guidelines at the AGS annual meeting. Patrice Wendling/Elsevier Global Medical News

CHICAGO — Vasculitis is less likely to kill affected patients than are complications arising from the drugs used to treat it. So thinking about vasculitis in terms of disease activity and disease damage may help avoid overtreatment.

In vasculitis, damage occurs in two peaks. The first is the direct result of the vasculitis itself, such as pulmonary fibrosis and renal insufficiency that are the direct consequence of disease flare. The second peak results from the untoward effects of therapies such as cyclophosphamide and glucocorticoids that accumulate in patients over time, Dr. Philip Seo said at a symposium sponsored by the American College of Rheumatology.

This accumulation of damage actually predicts increased mortality and is important in the way clinicians think about their patients when deciding what to do next, said Dr. Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.

“It's important to recognize in patients that there are manifestations that are clearly due to vasculitis that are not going to be amenable to immunosuppressive therapy, and really should not be treated as such,” he said. “Because the more immunosuppressive therapy you use, the more likely [patients] are to accrue damage as a consequence, and that just becomes an endless cycle.”

Data from the European Vasculitis (EUVAS) Study Group show that only 73% of patients with vasculitis were alive at 5 years. Impaired kidney function was a significant predictor of poor outcomes, whereas younger age was a clear benefit. Notably, vasculitis was not the No. 1 killer. The top three causes of death were infection, cardiovascular events, and malignancy, “all of which can relate back to the drugs we use to treat these patients,” said Dr. Seo, who reported no relevant conflicts of interest.

The WeCLOT (Wegener's Clinical Occurrence of Thrombosis) trial highlighted the increased risk of venous thromboembolism (VTE), reporting a VTE incidence rate of 7 per 100 person-years in 167 patients enrolled with active Wegener's granulomatosis and no prior VTE events (Ann. Intern. Med. 2005;142:620-5). To put this in context, patients with Wegener's are 23 times more likely than the general population to have a venous thromboembolic event and 7 times more likely to do so than patients with lupus, which is conventionally considered to be the prothrombotic disease, he said.

Perhaps less well known is the increased risk for solid malignancies. The 5-year follow-up data reported in 2008 from WGET (Wegener's Granulomatosis Etanercept Trial) showed a 4.4-fold increased risk of solid malignancies in patients with Wegener's who were treated with etanercept (Enbrel) and cyclophosphamide. It has been unclear whether this finding can be generalized beyond this population, but new unpublished data from 469 of 554 patients enrolled in the EUVAS Long-Term Follow-Up Study are moving in the same direction, Dr. Seo said. EUVAS investigators identified 31 solid malignancies (6.6%) including 8 prostate, 5 lung, and 4 bladder cancers, as well as 22 skin malignancies (3.8%).

Dr. Seo highlighted nasal blockade/chronic discharge/crusting (32%), hypertension (22%), hearing loss (20%), chronic sinusitis (12%), and osteoporosis (10%) as a short list of other common damage.

CHICAGO — Vasculitis is less likely to kill affected patients than are complications arising from the drugs used to treat it. So thinking about vasculitis in terms of disease activity and disease damage may help avoid overtreatment.

In vasculitis, damage occurs in two peaks. The first is the direct result of the vasculitis itself, such as pulmonary fibrosis and renal insufficiency that are the direct consequence of disease flare. The second peak results from the untoward effects of therapies such as cyclophosphamide and glucocorticoids that accumulate in patients over time, Dr. Philip Seo said at a symposium sponsored by the American College of Rheumatology.

This accumulation of damage actually predicts increased mortality and is important in the way clinicians think about their patients when deciding what to do next, said Dr. Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.

“It's important to recognize in patients that there are manifestations that are clearly due to vasculitis that are not going to be amenable to immunosuppressive therapy, and really should not be treated as such,” he said. “Because the more immunosuppressive therapy you use, the more likely [patients] are to accrue damage as a consequence, and that just becomes an endless cycle.”

Data from the European Vasculitis (EUVAS) Study Group show that only 73% of patients with vasculitis were alive at 5 years. Impaired kidney function was a significant predictor of poor outcomes, whereas younger age was a clear benefit. Notably, vasculitis was not the No. 1 killer. The top three causes of death were infection, cardiovascular events, and malignancy, “all of which can relate back to the drugs we use to treat these patients,” said Dr. Seo, who reported no relevant conflicts of interest.

The WeCLOT (Wegener's Clinical Occurrence of Thrombosis) trial highlighted the increased risk of venous thromboembolism (VTE), reporting a VTE incidence rate of 7 per 100 person-years in 167 patients enrolled with active Wegener's granulomatosis and no prior VTE events (Ann. Intern. Med. 2005;142:620-5). To put this in context, patients with Wegener's are 23 times more likely than the general population to have a venous thromboembolic event and 7 times more likely to do so than patients with lupus, which is conventionally considered to be the prothrombotic disease, he said.

Perhaps less well known is the increased risk for solid malignancies. The 5-year follow-up data reported in 2008 from WGET (Wegener's Granulomatosis Etanercept Trial) showed a 4.4-fold increased risk of solid malignancies in patients with Wegener's who were treated with etanercept (Enbrel) and cyclophosphamide. It has been unclear whether this finding can be generalized beyond this population, but new unpublished data from 469 of 554 patients enrolled in the EUVAS Long-Term Follow-Up Study are moving in the same direction, Dr. Seo said. EUVAS investigators identified 31 solid malignancies (6.6%) including 8 prostate, 5 lung, and 4 bladder cancers, as well as 22 skin malignancies (3.8%).

Dr. Seo highlighted nasal blockade/chronic discharge/crusting (32%), hypertension (22%), hearing loss (20%), chronic sinusitis (12%), and osteoporosis (10%) as a short list of other common damage.

CHICAGO — Vasculitis is less likely to kill affected patients than are complications arising from the drugs used to treat it. So thinking about vasculitis in terms of disease activity and disease damage may help avoid overtreatment.

In vasculitis, damage occurs in two peaks. The first is the direct result of the vasculitis itself, such as pulmonary fibrosis and renal insufficiency that are the direct consequence of disease flare. The second peak results from the untoward effects of therapies such as cyclophosphamide and glucocorticoids that accumulate in patients over time, Dr. Philip Seo said at a symposium sponsored by the American College of Rheumatology.

This accumulation of damage actually predicts increased mortality and is important in the way clinicians think about their patients when deciding what to do next, said Dr. Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.

“It's important to recognize in patients that there are manifestations that are clearly due to vasculitis that are not going to be amenable to immunosuppressive therapy, and really should not be treated as such,” he said. “Because the more immunosuppressive therapy you use, the more likely [patients] are to accrue damage as a consequence, and that just becomes an endless cycle.”

Data from the European Vasculitis (EUVAS) Study Group show that only 73% of patients with vasculitis were alive at 5 years. Impaired kidney function was a significant predictor of poor outcomes, whereas younger age was a clear benefit. Notably, vasculitis was not the No. 1 killer. The top three causes of death were infection, cardiovascular events, and malignancy, “all of which can relate back to the drugs we use to treat these patients,” said Dr. Seo, who reported no relevant conflicts of interest.

The WeCLOT (Wegener's Clinical Occurrence of Thrombosis) trial highlighted the increased risk of venous thromboembolism (VTE), reporting a VTE incidence rate of 7 per 100 person-years in 167 patients enrolled with active Wegener's granulomatosis and no prior VTE events (Ann. Intern. Med. 2005;142:620-5). To put this in context, patients with Wegener's are 23 times more likely than the general population to have a venous thromboembolic event and 7 times more likely to do so than patients with lupus, which is conventionally considered to be the prothrombotic disease, he said.

Perhaps less well known is the increased risk for solid malignancies. The 5-year follow-up data reported in 2008 from WGET (Wegener's Granulomatosis Etanercept Trial) showed a 4.4-fold increased risk of solid malignancies in patients with Wegener's who were treated with etanercept (Enbrel) and cyclophosphamide. It has been unclear whether this finding can be generalized beyond this population, but new unpublished data from 469 of 554 patients enrolled in the EUVAS Long-Term Follow-Up Study are moving in the same direction, Dr. Seo said. EUVAS investigators identified 31 solid malignancies (6.6%) including 8 prostate, 5 lung, and 4 bladder cancers, as well as 22 skin malignancies (3.8%).

Dr. Seo highlighted nasal blockade/chronic discharge/crusting (32%), hypertension (22%), hearing loss (20%), chronic sinusitis (12%), and osteoporosis (10%) as a short list of other common damage.

CHICAGO — Several pioneering treatment approaches have emerged to modify the vascular and fibrotic disease in scleroderma, Dr. Frederick Wigley said at a symposium sponsored by the American College of Rheumatology.

Dr. Wigley, director of the scleroderma center at Johns Hopkins University in Baltimore, discussed several of these novel therapies that are being studied and/or are in use, including the following:

▸ Bosentan. This endothelial inhibitor is approved in the United States and Europe to manage the symptoms of pulmonary artery hypertension (PAH). Two trials in scleroderma show that bosentan (Tracleer) reduces digital ulcers but has no benefit on Raynaud's attacks, Dr. Wigley said.

▸ Tyrosine kinase inhibition with imatinib mesylate. Industry-sponsored trials are underway evaluating imatinib (Gleevec) in systemic sclerosis and PAH, and dasatinib (Sprycel) in scleroderma pulmonary fibrosis.

▸ Immunoablation with and without stem cell transplantation. This should be looked at as “an experiment in progress,” Dr. Wigley said. In a pilot study of 34 patients with poor prognosis for systemic sclerosis, major improvements in skin and overall function were reported in 17 of 27 evaluable patients who survived 1 year after high-dose immunosuppressive treatment and autologous hematopoietic cell transplantation (Blood 2007;110:1388-96). These results came at a cost, however, with relapse occurring in 10 survivors and 23% of the 34 patients dying as a result of the procedure.

▸ Statins. These drugs have shown some benefit in early trials, possibly because they display pleiotropic effects on endothelial function that could potentially delay vascular injury. Levels of circulating endothelial precursor cells, reduced in scleroderma, were increased up to eightfold after 12 weeks of therapy with atorvastatin (Lipitor) 10 mg/day in 14 patients with systemic sclerosis in an open-label pilot study (Arthritis Rheum. 2006;54:1946-51). Endothelial markers improved and fewer new digital ulcers occurred with atorvastatin 40 mg/day for 16 weeks vs. placebo in 86 patients with scleroderma (J. Rheumatol. 2008;35:1801-8).

▸ ACE inhibitors. These agents have been shown to improve 12-month survival in patients with systemic scleroderma-induced renal disease, which is often associated with corticosteroids. ACE inhibitors can be used with angiotensin II receptor blockers (ARBs), calcium channel blockers, and prostaglandins when full doses of an ACE inhibitor do not control a crisis. The true benefits and risks of combining an ACE inhibitor with other agents in scleroderma have not been fully studied, Dr. Wigley said. ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial), which did not include scleroderma patients, showed that the use of combined ARBs and ACE inhibitors was associated with worse renal outcomes in high-risk patients.

▸ Prostaglandins. When administered intravenously, prostaglandins are an option for reducing digital ulcers, Raynaud's attacks, and PAH associated with scleroderma. Two trials are underway to evaluate oral formulations of iloprost and treprostinil in vascular scleroderma and Raynaud's, he said.

Dr. Wigley disclosed receiving research grants from MediQuest Therapeutics Inc., Novartis Pharmaceuticals Corp., and United Therapeutics Corp., and honoraria from MediQuest.

CHICAGO — Several pioneering treatment approaches have emerged to modify the vascular and fibrotic disease in scleroderma, Dr. Frederick Wigley said at a symposium sponsored by the American College of Rheumatology.

Dr. Wigley, director of the scleroderma center at Johns Hopkins University in Baltimore, discussed several of these novel therapies that are being studied and/or are in use, including the following:

▸ Bosentan. This endothelial inhibitor is approved in the United States and Europe to manage the symptoms of pulmonary artery hypertension (PAH). Two trials in scleroderma show that bosentan (Tracleer) reduces digital ulcers but has no benefit on Raynaud's attacks, Dr. Wigley said.

▸ Tyrosine kinase inhibition with imatinib mesylate. Industry-sponsored trials are underway evaluating imatinib (Gleevec) in systemic sclerosis and PAH, and dasatinib (Sprycel) in scleroderma pulmonary fibrosis.

▸ Immunoablation with and without stem cell transplantation. This should be looked at as “an experiment in progress,” Dr. Wigley said. In a pilot study of 34 patients with poor prognosis for systemic sclerosis, major improvements in skin and overall function were reported in 17 of 27 evaluable patients who survived 1 year after high-dose immunosuppressive treatment and autologous hematopoietic cell transplantation (Blood 2007;110:1388-96). These results came at a cost, however, with relapse occurring in 10 survivors and 23% of the 34 patients dying as a result of the procedure.

▸ Statins. These drugs have shown some benefit in early trials, possibly because they display pleiotropic effects on endothelial function that could potentially delay vascular injury. Levels of circulating endothelial precursor cells, reduced in scleroderma, were increased up to eightfold after 12 weeks of therapy with atorvastatin (Lipitor) 10 mg/day in 14 patients with systemic sclerosis in an open-label pilot study (Arthritis Rheum. 2006;54:1946-51). Endothelial markers improved and fewer new digital ulcers occurred with atorvastatin 40 mg/day for 16 weeks vs. placebo in 86 patients with scleroderma (J. Rheumatol. 2008;35:1801-8).

▸ ACE inhibitors. These agents have been shown to improve 12-month survival in patients with systemic scleroderma-induced renal disease, which is often associated with corticosteroids. ACE inhibitors can be used with angiotensin II receptor blockers (ARBs), calcium channel blockers, and prostaglandins when full doses of an ACE inhibitor do not control a crisis. The true benefits and risks of combining an ACE inhibitor with other agents in scleroderma have not been fully studied, Dr. Wigley said. ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial), which did not include scleroderma patients, showed that the use of combined ARBs and ACE inhibitors was associated with worse renal outcomes in high-risk patients.

▸ Prostaglandins. When administered intravenously, prostaglandins are an option for reducing digital ulcers, Raynaud's attacks, and PAH associated with scleroderma. Two trials are underway to evaluate oral formulations of iloprost and treprostinil in vascular scleroderma and Raynaud's, he said.

Dr. Wigley disclosed receiving research grants from MediQuest Therapeutics Inc., Novartis Pharmaceuticals Corp., and United Therapeutics Corp., and honoraria from MediQuest.

CHICAGO — Several pioneering treatment approaches have emerged to modify the vascular and fibrotic disease in scleroderma, Dr. Frederick Wigley said at a symposium sponsored by the American College of Rheumatology.

Dr. Wigley, director of the scleroderma center at Johns Hopkins University in Baltimore, discussed several of these novel therapies that are being studied and/or are in use, including the following:

▸ Bosentan. This endothelial inhibitor is approved in the United States and Europe to manage the symptoms of pulmonary artery hypertension (PAH). Two trials in scleroderma show that bosentan (Tracleer) reduces digital ulcers but has no benefit on Raynaud's attacks, Dr. Wigley said.

▸ Tyrosine kinase inhibition with imatinib mesylate. Industry-sponsored trials are underway evaluating imatinib (Gleevec) in systemic sclerosis and PAH, and dasatinib (Sprycel) in scleroderma pulmonary fibrosis.

▸ Immunoablation with and without stem cell transplantation. This should be looked at as “an experiment in progress,” Dr. Wigley said. In a pilot study of 34 patients with poor prognosis for systemic sclerosis, major improvements in skin and overall function were reported in 17 of 27 evaluable patients who survived 1 year after high-dose immunosuppressive treatment and autologous hematopoietic cell transplantation (Blood 2007;110:1388-96). These results came at a cost, however, with relapse occurring in 10 survivors and 23% of the 34 patients dying as a result of the procedure.

▸ Statins. These drugs have shown some benefit in early trials, possibly because they display pleiotropic effects on endothelial function that could potentially delay vascular injury. Levels of circulating endothelial precursor cells, reduced in scleroderma, were increased up to eightfold after 12 weeks of therapy with atorvastatin (Lipitor) 10 mg/day in 14 patients with systemic sclerosis in an open-label pilot study (Arthritis Rheum. 2006;54:1946-51). Endothelial markers improved and fewer new digital ulcers occurred with atorvastatin 40 mg/day for 16 weeks vs. placebo in 86 patients with scleroderma (J. Rheumatol. 2008;35:1801-8).

▸ ACE inhibitors. These agents have been shown to improve 12-month survival in patients with systemic scleroderma-induced renal disease, which is often associated with corticosteroids. ACE inhibitors can be used with angiotensin II receptor blockers (ARBs), calcium channel blockers, and prostaglandins when full doses of an ACE inhibitor do not control a crisis. The true benefits and risks of combining an ACE inhibitor with other agents in scleroderma have not been fully studied, Dr. Wigley said. ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial), which did not include scleroderma patients, showed that the use of combined ARBs and ACE inhibitors was associated with worse renal outcomes in high-risk patients.

▸ Prostaglandins. When administered intravenously, prostaglandins are an option for reducing digital ulcers, Raynaud's attacks, and PAH associated with scleroderma. Two trials are underway to evaluate oral formulations of iloprost and treprostinil in vascular scleroderma and Raynaud's, he said.

Dr. Wigley disclosed receiving research grants from MediQuest Therapeutics Inc., Novartis Pharmaceuticals Corp., and United Therapeutics Corp., and honoraria from MediQuest.

CHICAGO — Few rheumatologists would be fooled nowadays by gadolinium-induced nephrogenic systemic fibrosis, but there are other diseases that can masquerade as scleroderma.

The precise diagnosis of scleroderma-like illnesses is important because even though many of them are called scleroderma, they differ from systemic sclerosis in both treatment and outcome, Dr. Virginia Steen said at a symposium sponsored by the American College of Rheumatology.

The diagnosis is most often based on the distribution and clinical characteristics of skin findings, as biopsies don't always differentiate types of scleroderma. Rheumatologists would do well to keep in mind the following scleroderma mimics to avoid misdiagnosis:

▸ Lipodermatosclerosis is one condition that physicians often fail to think of as a scleroderma mimic. Also known as hypodermatitis sclerodermaformis, it refers to localized chronic inflammation and fibrosis of the skin and subcutaneous tissues of the lower leg. In the acute stage, the leg is inflamed and warm, the skin is very tight, and cellulitis may be present. The ankle and toes are not involved.

In its chronic stage, there is induration, contraction of the skin and subcutaneous tissues, and irregular depressions that can look almost identical to lower-leg scleroderma, she said. The leg eventually resembles an inverted champagne bottle, in which the upper half remains edematous and has a much greater circumference than does the lower sclerotic portion.

Lipodermatosclerosis is a sign of severe end-stage venous insufficiency, and should be differentiated from scleroderma, cellulitis, superficial thrombophlebitis, and erythema nodosum. The diagnosis is made from clinical observation, but direct immunofluorescence of early and late lesions has been used to show dermal pericapillary fibrin deposits.

If left untreated, lipodermatosclerosis can progress to ulceration, atrophy blanche, or shortening of the Achilles tendon. Treatment involves weight loss, controlling the underlying disease, and consistent wearing of support stockings that may need to be specially made, said Dr. Steen, professor of medicine and director of the rheumatology fellowship program at Georgetown University in Washington. Topical steroids are useful if the skin is inflamed, and antibiotics are recommended for cellulitis.

▸ Scleredema tends to target the upper body without affecting the lower extremities. Thickening occurs on the skin of the neck and face; severely affected patients are unable to wrinkle their foreheads or open their mouths. In most patients, the shawl sign is present, with skin involvement over the chest and arms, according to Dr. Steen.

Pathological features include swollen collagen with clear spaces and accumulation of hyaluronic acid and glycosaminoglycans. Although scleredema is commonly associated with diabetes, it can also occur after a viral illness. The treatment emphasis is on better diabetes control, but spontaneous resolution of symptoms is possible after infection.

▸ Eosinophilic fasciitis is a rare disorder characterized by symmetrical and painful inflammation and swelling of the extremities, leading to induration and the characteristic peau d'orange configuration. The palms may be involved, but typically the fingers and toes are spared. Contractures demonstrating the groove sign commonly evolve as a result of induration.

Eosinophilic fasciitis is slightly more common in middle-aged men, but can occur in women and children. It was initially distinguished from systemic sclerosis by the absence of Raynaud's phenomenon, autoantibodies, and visceral involvement, and—unlike systemic sclerosis—it responds to corticosteroids.

Histologically, there are marked eosinophilia and inflammatory infiltrates in the fascia. The extent of the histologic changes depends on the stage of the disease, and thus is not a consistent component of the disease. Aside from marked peripheral eosinophilia, other laboratory features to watch for include an increased erythrocyte sedimentation rate, increased gamma globulin, and an increased aldolase, with a normal creatinine phosphokinase.

Physical therapy is a key component of treatment, because this and most scleroderma mimics discussed here can cause joint contractures.

In eosinophilic fasciitis, low- to moderate-dose prednisone (20-30 mg)—and, if needed, methotrexate as a steroid-sparing agent—can be given. There is also some anecdotal evidence to suggest that rituximab (Rituxan), mycophenolate mofetil (CellCept), or tumor necrosis factor inhibitors may be useful, said Dr. Steen, who disclosed no conflicts of interest.

CHICAGO — Few rheumatologists would be fooled nowadays by gadolinium-induced nephrogenic systemic fibrosis, but there are other diseases that can masquerade as scleroderma.

The precise diagnosis of scleroderma-like illnesses is important because even though many of them are called scleroderma, they differ from systemic sclerosis in both treatment and outcome, Dr. Virginia Steen said at a symposium sponsored by the American College of Rheumatology.

The diagnosis is most often based on the distribution and clinical characteristics of skin findings, as biopsies don't always differentiate types of scleroderma. Rheumatologists would do well to keep in mind the following scleroderma mimics to avoid misdiagnosis:

▸ Lipodermatosclerosis is one condition that physicians often fail to think of as a scleroderma mimic. Also known as hypodermatitis sclerodermaformis, it refers to localized chronic inflammation and fibrosis of the skin and subcutaneous tissues of the lower leg. In the acute stage, the leg is inflamed and warm, the skin is very tight, and cellulitis may be present. The ankle and toes are not involved.

In its chronic stage, there is induration, contraction of the skin and subcutaneous tissues, and irregular depressions that can look almost identical to lower-leg scleroderma, she said. The leg eventually resembles an inverted champagne bottle, in which the upper half remains edematous and has a much greater circumference than does the lower sclerotic portion.

Lipodermatosclerosis is a sign of severe end-stage venous insufficiency, and should be differentiated from scleroderma, cellulitis, superficial thrombophlebitis, and erythema nodosum. The diagnosis is made from clinical observation, but direct immunofluorescence of early and late lesions has been used to show dermal pericapillary fibrin deposits.

If left untreated, lipodermatosclerosis can progress to ulceration, atrophy blanche, or shortening of the Achilles tendon. Treatment involves weight loss, controlling the underlying disease, and consistent wearing of support stockings that may need to be specially made, said Dr. Steen, professor of medicine and director of the rheumatology fellowship program at Georgetown University in Washington. Topical steroids are useful if the skin is inflamed, and antibiotics are recommended for cellulitis.

▸ Scleredema tends to target the upper body without affecting the lower extremities. Thickening occurs on the skin of the neck and face; severely affected patients are unable to wrinkle their foreheads or open their mouths. In most patients, the shawl sign is present, with skin involvement over the chest and arms, according to Dr. Steen.

Pathological features include swollen collagen with clear spaces and accumulation of hyaluronic acid and glycosaminoglycans. Although scleredema is commonly associated with diabetes, it can also occur after a viral illness. The treatment emphasis is on better diabetes control, but spontaneous resolution of symptoms is possible after infection.

▸ Eosinophilic fasciitis is a rare disorder characterized by symmetrical and painful inflammation and swelling of the extremities, leading to induration and the characteristic peau d'orange configuration. The palms may be involved, but typically the fingers and toes are spared. Contractures demonstrating the groove sign commonly evolve as a result of induration.

Eosinophilic fasciitis is slightly more common in middle-aged men, but can occur in women and children. It was initially distinguished from systemic sclerosis by the absence of Raynaud's phenomenon, autoantibodies, and visceral involvement, and—unlike systemic sclerosis—it responds to corticosteroids.

Histologically, there are marked eosinophilia and inflammatory infiltrates in the fascia. The extent of the histologic changes depends on the stage of the disease, and thus is not a consistent component of the disease. Aside from marked peripheral eosinophilia, other laboratory features to watch for include an increased erythrocyte sedimentation rate, increased gamma globulin, and an increased aldolase, with a normal creatinine phosphokinase.

Physical therapy is a key component of treatment, because this and most scleroderma mimics discussed here can cause joint contractures.

In eosinophilic fasciitis, low- to moderate-dose prednisone (20-30 mg)—and, if needed, methotrexate as a steroid-sparing agent—can be given. There is also some anecdotal evidence to suggest that rituximab (Rituxan), mycophenolate mofetil (CellCept), or tumor necrosis factor inhibitors may be useful, said Dr. Steen, who disclosed no conflicts of interest.

CHICAGO — Few rheumatologists would be fooled nowadays by gadolinium-induced nephrogenic systemic fibrosis, but there are other diseases that can masquerade as scleroderma.

The precise diagnosis of scleroderma-like illnesses is important because even though many of them are called scleroderma, they differ from systemic sclerosis in both treatment and outcome, Dr. Virginia Steen said at a symposium sponsored by the American College of Rheumatology.

The diagnosis is most often based on the distribution and clinical characteristics of skin findings, as biopsies don't always differentiate types of scleroderma. Rheumatologists would do well to keep in mind the following scleroderma mimics to avoid misdiagnosis:

▸ Lipodermatosclerosis is one condition that physicians often fail to think of as a scleroderma mimic. Also known as hypodermatitis sclerodermaformis, it refers to localized chronic inflammation and fibrosis of the skin and subcutaneous tissues of the lower leg. In the acute stage, the leg is inflamed and warm, the skin is very tight, and cellulitis may be present. The ankle and toes are not involved.

In its chronic stage, there is induration, contraction of the skin and subcutaneous tissues, and irregular depressions that can look almost identical to lower-leg scleroderma, she said. The leg eventually resembles an inverted champagne bottle, in which the upper half remains edematous and has a much greater circumference than does the lower sclerotic portion.

Lipodermatosclerosis is a sign of severe end-stage venous insufficiency, and should be differentiated from scleroderma, cellulitis, superficial thrombophlebitis, and erythema nodosum. The diagnosis is made from clinical observation, but direct immunofluorescence of early and late lesions has been used to show dermal pericapillary fibrin deposits.

If left untreated, lipodermatosclerosis can progress to ulceration, atrophy blanche, or shortening of the Achilles tendon. Treatment involves weight loss, controlling the underlying disease, and consistent wearing of support stockings that may need to be specially made, said Dr. Steen, professor of medicine and director of the rheumatology fellowship program at Georgetown University in Washington. Topical steroids are useful if the skin is inflamed, and antibiotics are recommended for cellulitis.

▸ Scleredema tends to target the upper body without affecting the lower extremities. Thickening occurs on the skin of the neck and face; severely affected patients are unable to wrinkle their foreheads or open their mouths. In most patients, the shawl sign is present, with skin involvement over the chest and arms, according to Dr. Steen.

Pathological features include swollen collagen with clear spaces and accumulation of hyaluronic acid and glycosaminoglycans. Although scleredema is commonly associated with diabetes, it can also occur after a viral illness. The treatment emphasis is on better diabetes control, but spontaneous resolution of symptoms is possible after infection.

▸ Eosinophilic fasciitis is a rare disorder characterized by symmetrical and painful inflammation and swelling of the extremities, leading to induration and the characteristic peau d'orange configuration. The palms may be involved, but typically the fingers and toes are spared. Contractures demonstrating the groove sign commonly evolve as a result of induration.

Eosinophilic fasciitis is slightly more common in middle-aged men, but can occur in women and children. It was initially distinguished from systemic sclerosis by the absence of Raynaud's phenomenon, autoantibodies, and visceral involvement, and—unlike systemic sclerosis—it responds to corticosteroids.

Histologically, there are marked eosinophilia and inflammatory infiltrates in the fascia. The extent of the histologic changes depends on the stage of the disease, and thus is not a consistent component of the disease. Aside from marked peripheral eosinophilia, other laboratory features to watch for include an increased erythrocyte sedimentation rate, increased gamma globulin, and an increased aldolase, with a normal creatinine phosphokinase.

Physical therapy is a key component of treatment, because this and most scleroderma mimics discussed here can cause joint contractures.

In eosinophilic fasciitis, low- to moderate-dose prednisone (20-30 mg)—and, if needed, methotrexate as a steroid-sparing agent—can be given. There is also some anecdotal evidence to suggest that rituximab (Rituxan), mycophenolate mofetil (CellCept), or tumor necrosis factor inhibitors may be useful, said Dr. Steen, who disclosed no conflicts of interest.

CHICAGO — Disease flare rather than infection or treatment complication may explain most cases of macrophage activation syndrome, and the wider use of new biologic agents may significantly reduce its incidence.

Epstein-Barr virus and cytomega-lovirus infections are the most commonly reported causes of macrophage activation syndrome (MAS), and several case reports have implicated gold preparations and sulfa drugs. But most cases of this potentially lethal complication of systemic juvenile idiopathic arthritis (JIA) have remained unexplained, pediatric rheumatologist Alexi Grom said at a symposium sponsored by the American College of Rheumatology.

“If we treat systemic JIA better with new biologics, we are less likely to see MAS because the underlying disease is the setup for this complication,” he said in an interview.

Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic JIA, affecting about 10% of these patients. It may occur at any stage of the disease, even in remission. Recent research suggests that a mild subclinical form of MAS may occur in about 30%-40% of children with active systemic JIA.

“Macrophage activation syndrome is the most devastating aspect” of JIA, Dr. Grom of Cincinnati Children's Hospital Medical Center told the audience.

There are strong clinical similarities between MAS and the genetic disorder familial hemophagocytic lymphohistiocytosis, both of which are characterized by uncontrolled proliferation of T cells and macrophages that exhibit hemophagocytic activity. Recent observations also suggest that dysfunction of the natural killer cell function is relevant to the pathogenesis of both disorders, Dr. Grom said. These cellular abnormalities in MAS patients result in a massive systemic inflammatory response marked by liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulopathy.

The first laboratory signs of MAS are sharp falls in white blood count, hemoglobin count, and platelet count, as well as some evidence of coagulopathy, including a significant elevation of D-dimers and alterations in clotting times. Because liver function is impaired, decreasing serum fibrinogen activity often results in a sharp fall in the erythrocyte sedimentation rate despite persistently elevated C-reactive protein, he said.

Two other important diagnostic features are hypertriglyceridemia, which reflects increased tumor necrosis factor-alpha activity, and extreme hyperferritinemia, with levels of serum ferritin in excess of 10,000 ng/mL in some patients. The diagnosis of MAS is typically confirmed with bone marrow studies, although Dr. Grom noted that abnormalities may not be evident in the early phase. Children with MAS often present with persistent fevers. They usually have enlarged nodes and hepatosplenomegaly, and at later stages bruising, purpura, and mucosal bleeding may be present. In severe cases, there are mental status changes or seizures.

There is no definitive treatment for MAS, but high-dose IV methylprednisolone (30 mg/kg; maximum, 1,000 mg), and cyclosporine oral or IV (2–5 mg/kg) are typically used. If the MAS severity does not lessen with this treatment, clinicians may want to consider chemotherapy with etoposide, which induces apoptosis of various immune cells including macrophages. Data show success with rabbit antithymocyte globulin, which takes aim at the T cells rather than the macrophages (Clin. Immunol. 2009 March 16 [Epub ahead of print]).

Dr. Grom reported no relevant conflicts of interest.

Subclinical MAS may occur in up to 40% of children with active JIA. Its more severe form is devastating. DR. GROM

CHICAGO — Disease flare rather than infection or treatment complication may explain most cases of macrophage activation syndrome, and the wider use of new biologic agents may significantly reduce its incidence.

Epstein-Barr virus and cytomega-lovirus infections are the most commonly reported causes of macrophage activation syndrome (MAS), and several case reports have implicated gold preparations and sulfa drugs. But most cases of this potentially lethal complication of systemic juvenile idiopathic arthritis (JIA) have remained unexplained, pediatric rheumatologist Alexi Grom said at a symposium sponsored by the American College of Rheumatology.

“If we treat systemic JIA better with new biologics, we are less likely to see MAS because the underlying disease is the setup for this complication,” he said in an interview.

Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic JIA, affecting about 10% of these patients. It may occur at any stage of the disease, even in remission. Recent research suggests that a mild subclinical form of MAS may occur in about 30%-40% of children with active systemic JIA.

“Macrophage activation syndrome is the most devastating aspect” of JIA, Dr. Grom of Cincinnati Children's Hospital Medical Center told the audience.

There are strong clinical similarities between MAS and the genetic disorder familial hemophagocytic lymphohistiocytosis, both of which are characterized by uncontrolled proliferation of T cells and macrophages that exhibit hemophagocytic activity. Recent observations also suggest that dysfunction of the natural killer cell function is relevant to the pathogenesis of both disorders, Dr. Grom said. These cellular abnormalities in MAS patients result in a massive systemic inflammatory response marked by liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulopathy.

The first laboratory signs of MAS are sharp falls in white blood count, hemoglobin count, and platelet count, as well as some evidence of coagulopathy, including a significant elevation of D-dimers and alterations in clotting times. Because liver function is impaired, decreasing serum fibrinogen activity often results in a sharp fall in the erythrocyte sedimentation rate despite persistently elevated C-reactive protein, he said.

Two other important diagnostic features are hypertriglyceridemia, which reflects increased tumor necrosis factor-alpha activity, and extreme hyperferritinemia, with levels of serum ferritin in excess of 10,000 ng/mL in some patients. The diagnosis of MAS is typically confirmed with bone marrow studies, although Dr. Grom noted that abnormalities may not be evident in the early phase. Children with MAS often present with persistent fevers. They usually have enlarged nodes and hepatosplenomegaly, and at later stages bruising, purpura, and mucosal bleeding may be present. In severe cases, there are mental status changes or seizures.

There is no definitive treatment for MAS, but high-dose IV methylprednisolone (30 mg/kg; maximum, 1,000 mg), and cyclosporine oral or IV (2–5 mg/kg) are typically used. If the MAS severity does not lessen with this treatment, clinicians may want to consider chemotherapy with etoposide, which induces apoptosis of various immune cells including macrophages. Data show success with rabbit antithymocyte globulin, which takes aim at the T cells rather than the macrophages (Clin. Immunol. 2009 March 16 [Epub ahead of print]).

Dr. Grom reported no relevant conflicts of interest.

Subclinical MAS may occur in up to 40% of children with active JIA. Its more severe form is devastating. DR. GROM

CHICAGO — Disease flare rather than infection or treatment complication may explain most cases of macrophage activation syndrome, and the wider use of new biologic agents may significantly reduce its incidence.

Epstein-Barr virus and cytomega-lovirus infections are the most commonly reported causes of macrophage activation syndrome (MAS), and several case reports have implicated gold preparations and sulfa drugs. But most cases of this potentially lethal complication of systemic juvenile idiopathic arthritis (JIA) have remained unexplained, pediatric rheumatologist Alexi Grom said at a symposium sponsored by the American College of Rheumatology.

“If we treat systemic JIA better with new biologics, we are less likely to see MAS because the underlying disease is the setup for this complication,” he said in an interview.

Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic JIA, affecting about 10% of these patients. It may occur at any stage of the disease, even in remission. Recent research suggests that a mild subclinical form of MAS may occur in about 30%-40% of children with active systemic JIA.

“Macrophage activation syndrome is the most devastating aspect” of JIA, Dr. Grom of Cincinnati Children's Hospital Medical Center told the audience.

There are strong clinical similarities between MAS and the genetic disorder familial hemophagocytic lymphohistiocytosis, both of which are characterized by uncontrolled proliferation of T cells and macrophages that exhibit hemophagocytic activity. Recent observations also suggest that dysfunction of the natural killer cell function is relevant to the pathogenesis of both disorders, Dr. Grom said. These cellular abnormalities in MAS patients result in a massive systemic inflammatory response marked by liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulopathy.

The first laboratory signs of MAS are sharp falls in white blood count, hemoglobin count, and platelet count, as well as some evidence of coagulopathy, including a significant elevation of D-dimers and alterations in clotting times. Because liver function is impaired, decreasing serum fibrinogen activity often results in a sharp fall in the erythrocyte sedimentation rate despite persistently elevated C-reactive protein, he said.

Two other important diagnostic features are hypertriglyceridemia, which reflects increased tumor necrosis factor-alpha activity, and extreme hyperferritinemia, with levels of serum ferritin in excess of 10,000 ng/mL in some patients. The diagnosis of MAS is typically confirmed with bone marrow studies, although Dr. Grom noted that abnormalities may not be evident in the early phase. Children with MAS often present with persistent fevers. They usually have enlarged nodes and hepatosplenomegaly, and at later stages bruising, purpura, and mucosal bleeding may be present. In severe cases, there are mental status changes or seizures.

There is no definitive treatment for MAS, but high-dose IV methylprednisolone (30 mg/kg; maximum, 1,000 mg), and cyclosporine oral or IV (2–5 mg/kg) are typically used. If the MAS severity does not lessen with this treatment, clinicians may want to consider chemotherapy with etoposide, which induces apoptosis of various immune cells including macrophages. Data show success with rabbit antithymocyte globulin, which takes aim at the T cells rather than the macrophages (Clin. Immunol. 2009 March 16 [Epub ahead of print]).

Dr. Grom reported no relevant conflicts of interest.

Subclinical MAS may occur in up to 40% of children with active JIA. Its more severe form is devastating. DR. GROM

CHICAGO — Oxybutynin chloride topical gel provides a novel treatment option for patients with overactive bladder, according to the findings of a randomized, multicenter phase III study.

In the trial, 24% of 246 patients, younger than age 65 years, with overactive bladder who applied 1 g of oxybutynin gel once daily achieved complete urinary continence at 12 weeks, compared with 17% of 260 age-matched placebo-treated patients.

Among those participants who were aged 65 years or older, 34% of 143 patients using oxybutynin were continent at 12 weeks compared with 18% of 140 patients using placebo, Dr. Norman Zinner reported in a poster at the annual meeting of the American Geriatrics Society.

Oxybutynin (Gelnique) 10% gel was approved for treating overactive bladder.

Most of the study participants were white women, with a mean duration of incontinence of about 7.5 years. In patients younger than 65 years, oxybutynin gel achieved a significantly greater reduction than placebo in average number of daily incontinence episodes (−3.2 vs. −2.6 per day), said Dr. Zinner, a urologist with Western Clinical Research Inc. in Torrance, Calif. In patients 65 years and older, oxybutynin gel resulted in a greater reduction than placebo in daily incontinence episodes (−2.6 vs. −2.2), but the difference between groups was not significant.

Possible side effects from oxybutynin gel include dry mouth and dizziness.

Dr. Zinner is on the speakers and advisory boards for Watson Laboratories, which manufacturers oxybutynin gel. His colleagues are Watson employees.

CHICAGO — Oxybutynin chloride topical gel provides a novel treatment option for patients with overactive bladder, according to the findings of a randomized, multicenter phase III study.

In the trial, 24% of 246 patients, younger than age 65 years, with overactive bladder who applied 1 g of oxybutynin gel once daily achieved complete urinary continence at 12 weeks, compared with 17% of 260 age-matched placebo-treated patients.

Among those participants who were aged 65 years or older, 34% of 143 patients using oxybutynin were continent at 12 weeks compared with 18% of 140 patients using placebo, Dr. Norman Zinner reported in a poster at the annual meeting of the American Geriatrics Society.

Oxybutynin (Gelnique) 10% gel was approved for treating overactive bladder.

Most of the study participants were white women, with a mean duration of incontinence of about 7.5 years. In patients younger than 65 years, oxybutynin gel achieved a significantly greater reduction than placebo in average number of daily incontinence episodes (−3.2 vs. −2.6 per day), said Dr. Zinner, a urologist with Western Clinical Research Inc. in Torrance, Calif. In patients 65 years and older, oxybutynin gel resulted in a greater reduction than placebo in daily incontinence episodes (−2.6 vs. −2.2), but the difference between groups was not significant.

Possible side effects from oxybutynin gel include dry mouth and dizziness.

Dr. Zinner is on the speakers and advisory boards for Watson Laboratories, which manufacturers oxybutynin gel. His colleagues are Watson employees.

CHICAGO — Oxybutynin chloride topical gel provides a novel treatment option for patients with overactive bladder, according to the findings of a randomized, multicenter phase III study.

In the trial, 24% of 246 patients, younger than age 65 years, with overactive bladder who applied 1 g of oxybutynin gel once daily achieved complete urinary continence at 12 weeks, compared with 17% of 260 age-matched placebo-treated patients.

Among those participants who were aged 65 years or older, 34% of 143 patients using oxybutynin were continent at 12 weeks compared with 18% of 140 patients using placebo, Dr. Norman Zinner reported in a poster at the annual meeting of the American Geriatrics Society.

Oxybutynin (Gelnique) 10% gel was approved for treating overactive bladder.

Most of the study participants were white women, with a mean duration of incontinence of about 7.5 years. In patients younger than 65 years, oxybutynin gel achieved a significantly greater reduction than placebo in average number of daily incontinence episodes (−3.2 vs. −2.6 per day), said Dr. Zinner, a urologist with Western Clinical Research Inc. in Torrance, Calif. In patients 65 years and older, oxybutynin gel resulted in a greater reduction than placebo in daily incontinence episodes (−2.6 vs. −2.2), but the difference between groups was not significant.

Possible side effects from oxybutynin gel include dry mouth and dizziness.

Dr. Zinner is on the speakers and advisory boards for Watson Laboratories, which manufacturers oxybutynin gel. His colleagues are Watson employees.

CHICAGO — A brief exercise program reduced agitated behavior in a pilot study of 50 nursing home residents with severe cognitive impairment.

Other studies have already shown that exercise programs can reduce agitation and depression, and improve the ability to perform activities of daily living.

The current study involved 30 minutes of supervised exercise for 3 days per week for 3 weeks. Residents of locked special needs units at two nursing homes walked outdoors for 15 minutes in large groups and did 5 minutes each of weight lifting, sitting and standing, and throwing a beach ball in small groups.

At baseline, the mean St. Louis Mental Status Examination score among the 50 residents was 1.45 on a 30-point scale, with a score of 30 indicating full cognitive faculty.

Mean Pittsburgh Agitation Scale (PAS) scores improved significantly from 5.8 at baseline to 4.5 post-intervention on a 16-point scale, with 0 meaning no agitation, Edris Aman reported at the annual meeting of the American Geriatrics Society.

Those categorized with the highest PAS scores at baseline had the largest reductions in PAS scores falling from a mean score of 9.1 to 6.1.

“When you have a structured exercise program it seems like it kind of changes the way they think, especially when they interact one-on-one” said Mr. Aman, a medical student at St. Louis University School of Medicine in Missouri.

Continuous activity programming, in which residents are engaged in meaningful activities like exercise or casual conversation whenever they are in the main activity area, has been shown to reduce the number of days with agitation and psychoactive medication use and improve sleep in two dementia special care units (J. Am. Med. Dir. Assoc. 2006 Sep;7:426–31).

Mr. Aman said that anecdotally nurses reported that after a week of exercising patients who were previously up all night began sleeping through the night and remaining awake during the day.

Mr. Aman reported no conflicts of interest. The study was funded by a grant from the American Foundation for Aging Research.

CHICAGO — A brief exercise program reduced agitated behavior in a pilot study of 50 nursing home residents with severe cognitive impairment.

Other studies have already shown that exercise programs can reduce agitation and depression, and improve the ability to perform activities of daily living.

The current study involved 30 minutes of supervised exercise for 3 days per week for 3 weeks. Residents of locked special needs units at two nursing homes walked outdoors for 15 minutes in large groups and did 5 minutes each of weight lifting, sitting and standing, and throwing a beach ball in small groups.

At baseline, the mean St. Louis Mental Status Examination score among the 50 residents was 1.45 on a 30-point scale, with a score of 30 indicating full cognitive faculty.

Mean Pittsburgh Agitation Scale (PAS) scores improved significantly from 5.8 at baseline to 4.5 post-intervention on a 16-point scale, with 0 meaning no agitation, Edris Aman reported at the annual meeting of the American Geriatrics Society.

Those categorized with the highest PAS scores at baseline had the largest reductions in PAS scores falling from a mean score of 9.1 to 6.1.

“When you have a structured exercise program it seems like it kind of changes the way they think, especially when they interact one-on-one” said Mr. Aman, a medical student at St. Louis University School of Medicine in Missouri.

Continuous activity programming, in which residents are engaged in meaningful activities like exercise or casual conversation whenever they are in the main activity area, has been shown to reduce the number of days with agitation and psychoactive medication use and improve sleep in two dementia special care units (J. Am. Med. Dir. Assoc. 2006 Sep;7:426–31).

Mr. Aman said that anecdotally nurses reported that after a week of exercising patients who were previously up all night began sleeping through the night and remaining awake during the day.

Mr. Aman reported no conflicts of interest. The study was funded by a grant from the American Foundation for Aging Research.

CHICAGO — A brief exercise program reduced agitated behavior in a pilot study of 50 nursing home residents with severe cognitive impairment.

Other studies have already shown that exercise programs can reduce agitation and depression, and improve the ability to perform activities of daily living.

The current study involved 30 minutes of supervised exercise for 3 days per week for 3 weeks. Residents of locked special needs units at two nursing homes walked outdoors for 15 minutes in large groups and did 5 minutes each of weight lifting, sitting and standing, and throwing a beach ball in small groups.

At baseline, the mean St. Louis Mental Status Examination score among the 50 residents was 1.45 on a 30-point scale, with a score of 30 indicating full cognitive faculty.

Mean Pittsburgh Agitation Scale (PAS) scores improved significantly from 5.8 at baseline to 4.5 post-intervention on a 16-point scale, with 0 meaning no agitation, Edris Aman reported at the annual meeting of the American Geriatrics Society.

Those categorized with the highest PAS scores at baseline had the largest reductions in PAS scores falling from a mean score of 9.1 to 6.1.

“When you have a structured exercise program it seems like it kind of changes the way they think, especially when they interact one-on-one” said Mr. Aman, a medical student at St. Louis University School of Medicine in Missouri.

Continuous activity programming, in which residents are engaged in meaningful activities like exercise or casual conversation whenever they are in the main activity area, has been shown to reduce the number of days with agitation and psychoactive medication use and improve sleep in two dementia special care units (J. Am. Med. Dir. Assoc. 2006 Sep;7:426–31).

Mr. Aman said that anecdotally nurses reported that after a week of exercising patients who were previously up all night began sleeping through the night and remaining awake during the day.

Mr. Aman reported no conflicts of interest. The study was funded by a grant from the American Foundation for Aging Research.

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs, such as aspirin or ibuprofen, or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Traditional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths yearly attributed to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the Veterans Affairs Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037–45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a traditional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the traditional NSAID alone (Curr. Opin. Rheumatol. 2008;20:239–45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

The recommendations are based on a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The update is to be published in the Journal of the American Geriatrics Society.

Dr. Katz has served as a consultant for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine is as a consultant or speaker for numerous pharmaceutical companies and has interests in Johnson & Johnson and Cephalon Inc.

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs, such as aspirin or ibuprofen, or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Traditional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths yearly attributed to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the Veterans Affairs Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037–45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a traditional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the traditional NSAID alone (Curr. Opin. Rheumatol. 2008;20:239–45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

The recommendations are based on a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The update is to be published in the Journal of the American Geriatrics Society.

Dr. Katz has served as a consultant for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine is as a consultant or speaker for numerous pharmaceutical companies and has interests in Johnson & Johnson and Cephalon Inc.

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs, such as aspirin or ibuprofen, or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Traditional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths yearly attributed to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the Veterans Affairs Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037–45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a traditional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the traditional NSAID alone (Curr. Opin. Rheumatol. 2008;20:239–45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

The recommendations are based on a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The update is to be published in the Journal of the American Geriatrics Society.

Dr. Katz has served as a consultant for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine is as a consultant or speaker for numerous pharmaceutical companies and has interests in Johnson & Johnson and Cephalon Inc.