Rheumatoid Arthritis

ATLANTA – Women with Lyme disease display more clinical symptoms than do men with the disease and also are less likely to seroconvert following treatment, according to findings from a prospective cohort study involving 77 patients.

Numerous symptoms were reported more often by the 37 women in the study than by the 40 men. For example, significantly more women than men reported joint pain, muscle pain, headache, back pain, heart palpitations, nausea, vomiting, anxiety, numbness and tingling, and changes in vision during at least one of six preplanned study visits with a physician, Lauren A. Crowder, M.P.H. reported in a poster at the International Conference on Emerging Infectious Diseases.

Photo courtesy Janice Haney Carr/CDC

Joint pain, heart palpitations, nausea, vomiting, and changes in vision were reported significantly more often by women at two of the six visits, and headache was reported significantly more often by women at four of the six visits.

"The second preliminary finding we observed in our cohort of patients was that women were less likely to seroconvert on the antibody tests for serodiagnosis of Lyme disease," Ms. Crowder of the Lyme Disease Research Foundation, Lutherville, Md., said in an interview.

At the initial study visit, a similar proportion of men and women (about 60% of each) tested negative for Lyme disease using the Centers for Disease Control and Prevention’s recommended two-tier testing criteria for serodiagnosis. However, at the second visit, which was performed immediately post treatment, 70% of women who tested negative at the first visit remained negative, compared with only 35% of the men who initially tested negative.

Additionally, polychromatic flow cytometry performed on patient samples indicated that women had significantly higher frequency of CD4+CCR5+ T-cells prior to treatment than did men (mean of 9.82% vs. 5.96%).

"These findings suggest to us that there may be a difference between how men and women respond to infection with Lyme disease. One hypothesis for these differences is that there may be an immunological variation in response to Borrelia burgdorferi, the bacterial infection that causes Lyme disease, between men and women," Ms. Crowder said.

Study participants had early, untreated erythema migrans and clinically confirmed Lyme disease. At the first of the six study visits, they were tested using the CDC criteria by a commercial laboratory. All were treated with 3-week course of doxycycline and were then followed for up to 2 years. At each study visit, participants underwent a physical examination and interval history, reported clinical symptoms and completed self-administered surveys, and underwent repeat laboratory evaluations.

The findings highlight a need for additional research on sex-based differences in the effects of early Lyme disease. Such differences have been seen in other infectious disease, but have not been thoroughly explored in early Lyme disease, Ms. Crowder noted.

Such study is important given that Lyme disease is the most common vector-borne infectious disease in the United States. Although most patients recover from acute infection with proper antibiotic treatment, a subset of patients develop Post-Treatment Lyme Disease Syndrome. The CDC defines this syndrome as involving lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months.

"We will continue to explore these suggested differences both in this cohort and in future research studies," she said.

Ms. Crowder also stressed the importance of encouraging patients to look for ticks if they live in Lyme endemic areas.

This study was supported by the Lyme Disease Research Foundation. Ms. Crowder had no disclosures to report.

ATLANTA – Women with Lyme disease display more clinical symptoms than do men with the disease and also are less likely to seroconvert following treatment, according to findings from a prospective cohort study involving 77 patients.

Numerous symptoms were reported more often by the 37 women in the study than by the 40 men. For example, significantly more women than men reported joint pain, muscle pain, headache, back pain, heart palpitations, nausea, vomiting, anxiety, numbness and tingling, and changes in vision during at least one of six preplanned study visits with a physician, Lauren A. Crowder, M.P.H. reported in a poster at the International Conference on Emerging Infectious Diseases.

Photo courtesy Janice Haney Carr/CDC

Joint pain, heart palpitations, nausea, vomiting, and changes in vision were reported significantly more often by women at two of the six visits, and headache was reported significantly more often by women at four of the six visits.

"The second preliminary finding we observed in our cohort of patients was that women were less likely to seroconvert on the antibody tests for serodiagnosis of Lyme disease," Ms. Crowder of the Lyme Disease Research Foundation, Lutherville, Md., said in an interview.

At the initial study visit, a similar proportion of men and women (about 60% of each) tested negative for Lyme disease using the Centers for Disease Control and Prevention’s recommended two-tier testing criteria for serodiagnosis. However, at the second visit, which was performed immediately post treatment, 70% of women who tested negative at the first visit remained negative, compared with only 35% of the men who initially tested negative.

Additionally, polychromatic flow cytometry performed on patient samples indicated that women had significantly higher frequency of CD4+CCR5+ T-cells prior to treatment than did men (mean of 9.82% vs. 5.96%).

"These findings suggest to us that there may be a difference between how men and women respond to infection with Lyme disease. One hypothesis for these differences is that there may be an immunological variation in response to Borrelia burgdorferi, the bacterial infection that causes Lyme disease, between men and women," Ms. Crowder said.

Study participants had early, untreated erythema migrans and clinically confirmed Lyme disease. At the first of the six study visits, they were tested using the CDC criteria by a commercial laboratory. All were treated with 3-week course of doxycycline and were then followed for up to 2 years. At each study visit, participants underwent a physical examination and interval history, reported clinical symptoms and completed self-administered surveys, and underwent repeat laboratory evaluations.

The findings highlight a need for additional research on sex-based differences in the effects of early Lyme disease. Such differences have been seen in other infectious disease, but have not been thoroughly explored in early Lyme disease, Ms. Crowder noted.

Such study is important given that Lyme disease is the most common vector-borne infectious disease in the United States. Although most patients recover from acute infection with proper antibiotic treatment, a subset of patients develop Post-Treatment Lyme Disease Syndrome. The CDC defines this syndrome as involving lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months.

"We will continue to explore these suggested differences both in this cohort and in future research studies," she said.

Ms. Crowder also stressed the importance of encouraging patients to look for ticks if they live in Lyme endemic areas.

This study was supported by the Lyme Disease Research Foundation. Ms. Crowder had no disclosures to report.

ATLANTA – Women with Lyme disease display more clinical symptoms than do men with the disease and also are less likely to seroconvert following treatment, according to findings from a prospective cohort study involving 77 patients.

Numerous symptoms were reported more often by the 37 women in the study than by the 40 men. For example, significantly more women than men reported joint pain, muscle pain, headache, back pain, heart palpitations, nausea, vomiting, anxiety, numbness and tingling, and changes in vision during at least one of six preplanned study visits with a physician, Lauren A. Crowder, M.P.H. reported in a poster at the International Conference on Emerging Infectious Diseases.

Photo courtesy Janice Haney Carr/CDC

Joint pain, heart palpitations, nausea, vomiting, and changes in vision were reported significantly more often by women at two of the six visits, and headache was reported significantly more often by women at four of the six visits.

"The second preliminary finding we observed in our cohort of patients was that women were less likely to seroconvert on the antibody tests for serodiagnosis of Lyme disease," Ms. Crowder of the Lyme Disease Research Foundation, Lutherville, Md., said in an interview.

At the initial study visit, a similar proportion of men and women (about 60% of each) tested negative for Lyme disease using the Centers for Disease Control and Prevention’s recommended two-tier testing criteria for serodiagnosis. However, at the second visit, which was performed immediately post treatment, 70% of women who tested negative at the first visit remained negative, compared with only 35% of the men who initially tested negative.

Additionally, polychromatic flow cytometry performed on patient samples indicated that women had significantly higher frequency of CD4+CCR5+ T-cells prior to treatment than did men (mean of 9.82% vs. 5.96%).

"These findings suggest to us that there may be a difference between how men and women respond to infection with Lyme disease. One hypothesis for these differences is that there may be an immunological variation in response to Borrelia burgdorferi, the bacterial infection that causes Lyme disease, between men and women," Ms. Crowder said.

Study participants had early, untreated erythema migrans and clinically confirmed Lyme disease. At the first of the six study visits, they were tested using the CDC criteria by a commercial laboratory. All were treated with 3-week course of doxycycline and were then followed for up to 2 years. At each study visit, participants underwent a physical examination and interval history, reported clinical symptoms and completed self-administered surveys, and underwent repeat laboratory evaluations.

The findings highlight a need for additional research on sex-based differences in the effects of early Lyme disease. Such differences have been seen in other infectious disease, but have not been thoroughly explored in early Lyme disease, Ms. Crowder noted.

Such study is important given that Lyme disease is the most common vector-borne infectious disease in the United States. Although most patients recover from acute infection with proper antibiotic treatment, a subset of patients develop Post-Treatment Lyme Disease Syndrome. The CDC defines this syndrome as involving lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months.

"We will continue to explore these suggested differences both in this cohort and in future research studies," she said.

Ms. Crowder also stressed the importance of encouraging patients to look for ticks if they live in Lyme endemic areas.

This study was supported by the Lyme Disease Research Foundation. Ms. Crowder had no disclosures to report.

WAIKOLOA, HAWAII – Extramammary Paget’s disease poses a particular challenge because of its multifocal/multicentric nature.

"What you see with extramammary Paget’s is not necessarily what you get," Dr. Theodore Rosen cautioned at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Bruce Jancin/IMNG Medical Media

This is an uncommon neoplasia that’s typically described as an erythematous, erosive, itchy patch or plaque having a strawberries-and-cream appearance. Yet there may be other areas of subclinical involvement at a distance from the obvious lesion.

"That’s why Mohs surgery for this condition may be difficult without something being done in advance," said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

He suggested applying topical 5% imiquimod or 5-fluorouracil to identify all of the active foci by lighting up the affected areas to allow more precise surgery or ablative therapy.

Dr. Rosen does not, however, recommend using imiquimod as primary therapy. He noted that a review of 27 published cases of 5% imiquimod for the treatment of extramammary Paget’s disease reported a 22% failure rate (Arch. Dermatol. 2011;147:704-8).

Mohs surgery shows promise for treatment of extramammary Paget’s disease, with lower recurrence rates than reported for wide surgical excision. However, experience to date with Mohs surgery for extensive disease is limited. For this reason, most authorities still consider wide surgical excision the gold standard therapy for extramammary Paget’s disease, despite published recurrence rates of 42%-54% even with clear surgical margins. Use of preoperative topical 5-fluorouracil or 5% imiquimod should substantially reduce those high recurrence rates, the dermatologist said.

Extramammary Paget’s disease is typically slow-growing for a decade or more before invading the dermis, at which point it quickly becomes widely metastatic.

"Once extramammary Paget’s disease has broken through the dermal/epidermal junction, it becomes a very nasty, bad-acting disease," Dr. Rosen said.

It’s well recognized that extramammary Paget’s is associated with an increased risk of underlying internal malignancy of the lower gastrointestinal or genitourinary tract. This increased risk is typically described as being in the 10%-20% range. But that figure may be too low. A recent report from investigators at Houston’s M.D. Anderson Cancer Center involving 20 consecutive patients with extramammary Paget’s on the penis or scrotum indicated that 8 of them – fully 40% – had an associated underlying internal adenocarcinoma (J. Urol. 2011;186:97-102).

The risk of underlying internal malignancy is known to be considerably greater in white patients than in Asians. It’s very uncommon for black patients with extramammary Paget’s to have an associated internal malignancy.

Because the full workup for an associated occult internal adenocarcinoma is elaborate and costly, a means of determining which patients are at greater or lesser risk would be welcome in order to guide the extent of testing. Cytokeratin staining may be the solution. Spanish dermatologists have reported that cutaneous extramammary Paget’s disease is characteristically positive for cytokeratin 7, negative for cytokeratin 20, and positive for cystic disease fluid protein 15.

In contrast, endodermal extramammary Paget’s, which is more strongly associated with internal malignancy, is positive for cytokeratin 7 and 20 and negative for cystic disease fluid protein 15, according to the investigators (Clin. Exp. Dermatol. 2008;33:595-8). A cautionary note: Dr. Rosen said that to his knowledge these findings haven’t yet been confirmed by other groups.

He reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Extramammary Paget’s disease poses a particular challenge because of its multifocal/multicentric nature.

"What you see with extramammary Paget’s is not necessarily what you get," Dr. Theodore Rosen cautioned at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Bruce Jancin/IMNG Medical Media

This is an uncommon neoplasia that’s typically described as an erythematous, erosive, itchy patch or plaque having a strawberries-and-cream appearance. Yet there may be other areas of subclinical involvement at a distance from the obvious lesion.

"That’s why Mohs surgery for this condition may be difficult without something being done in advance," said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

He suggested applying topical 5% imiquimod or 5-fluorouracil to identify all of the active foci by lighting up the affected areas to allow more precise surgery or ablative therapy.

Dr. Rosen does not, however, recommend using imiquimod as primary therapy. He noted that a review of 27 published cases of 5% imiquimod for the treatment of extramammary Paget’s disease reported a 22% failure rate (Arch. Dermatol. 2011;147:704-8).

Mohs surgery shows promise for treatment of extramammary Paget’s disease, with lower recurrence rates than reported for wide surgical excision. However, experience to date with Mohs surgery for extensive disease is limited. For this reason, most authorities still consider wide surgical excision the gold standard therapy for extramammary Paget’s disease, despite published recurrence rates of 42%-54% even with clear surgical margins. Use of preoperative topical 5-fluorouracil or 5% imiquimod should substantially reduce those high recurrence rates, the dermatologist said.

Extramammary Paget’s disease is typically slow-growing for a decade or more before invading the dermis, at which point it quickly becomes widely metastatic.

"Once extramammary Paget’s disease has broken through the dermal/epidermal junction, it becomes a very nasty, bad-acting disease," Dr. Rosen said.

It’s well recognized that extramammary Paget’s is associated with an increased risk of underlying internal malignancy of the lower gastrointestinal or genitourinary tract. This increased risk is typically described as being in the 10%-20% range. But that figure may be too low. A recent report from investigators at Houston’s M.D. Anderson Cancer Center involving 20 consecutive patients with extramammary Paget’s on the penis or scrotum indicated that 8 of them – fully 40% – had an associated underlying internal adenocarcinoma (J. Urol. 2011;186:97-102).

The risk of underlying internal malignancy is known to be considerably greater in white patients than in Asians. It’s very uncommon for black patients with extramammary Paget’s to have an associated internal malignancy.

Because the full workup for an associated occult internal adenocarcinoma is elaborate and costly, a means of determining which patients are at greater or lesser risk would be welcome in order to guide the extent of testing. Cytokeratin staining may be the solution. Spanish dermatologists have reported that cutaneous extramammary Paget’s disease is characteristically positive for cytokeratin 7, negative for cytokeratin 20, and positive for cystic disease fluid protein 15.

In contrast, endodermal extramammary Paget’s, which is more strongly associated with internal malignancy, is positive for cytokeratin 7 and 20 and negative for cystic disease fluid protein 15, according to the investigators (Clin. Exp. Dermatol. 2008;33:595-8). A cautionary note: Dr. Rosen said that to his knowledge these findings haven’t yet been confirmed by other groups.

He reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Extramammary Paget’s disease poses a particular challenge because of its multifocal/multicentric nature.

"What you see with extramammary Paget’s is not necessarily what you get," Dr. Theodore Rosen cautioned at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Bruce Jancin/IMNG Medical Media

This is an uncommon neoplasia that’s typically described as an erythematous, erosive, itchy patch or plaque having a strawberries-and-cream appearance. Yet there may be other areas of subclinical involvement at a distance from the obvious lesion.

"That’s why Mohs surgery for this condition may be difficult without something being done in advance," said Dr. Rosen, professor of dermatology at Baylor College of Medicine, Houston.

He suggested applying topical 5% imiquimod or 5-fluorouracil to identify all of the active foci by lighting up the affected areas to allow more precise surgery or ablative therapy.

Dr. Rosen does not, however, recommend using imiquimod as primary therapy. He noted that a review of 27 published cases of 5% imiquimod for the treatment of extramammary Paget’s disease reported a 22% failure rate (Arch. Dermatol. 2011;147:704-8).

Mohs surgery shows promise for treatment of extramammary Paget’s disease, with lower recurrence rates than reported for wide surgical excision. However, experience to date with Mohs surgery for extensive disease is limited. For this reason, most authorities still consider wide surgical excision the gold standard therapy for extramammary Paget’s disease, despite published recurrence rates of 42%-54% even with clear surgical margins. Use of preoperative topical 5-fluorouracil or 5% imiquimod should substantially reduce those high recurrence rates, the dermatologist said.

Extramammary Paget’s disease is typically slow-growing for a decade or more before invading the dermis, at which point it quickly becomes widely metastatic.

"Once extramammary Paget’s disease has broken through the dermal/epidermal junction, it becomes a very nasty, bad-acting disease," Dr. Rosen said.

It’s well recognized that extramammary Paget’s is associated with an increased risk of underlying internal malignancy of the lower gastrointestinal or genitourinary tract. This increased risk is typically described as being in the 10%-20% range. But that figure may be too low. A recent report from investigators at Houston’s M.D. Anderson Cancer Center involving 20 consecutive patients with extramammary Paget’s on the penis or scrotum indicated that 8 of them – fully 40% – had an associated underlying internal adenocarcinoma (J. Urol. 2011;186:97-102).

The risk of underlying internal malignancy is known to be considerably greater in white patients than in Asians. It’s very uncommon for black patients with extramammary Paget’s to have an associated internal malignancy.

Because the full workup for an associated occult internal adenocarcinoma is elaborate and costly, a means of determining which patients are at greater or lesser risk would be welcome in order to guide the extent of testing. Cytokeratin staining may be the solution. Spanish dermatologists have reported that cutaneous extramammary Paget’s disease is characteristically positive for cytokeratin 7, negative for cytokeratin 20, and positive for cystic disease fluid protein 15.

In contrast, endodermal extramammary Paget’s, which is more strongly associated with internal malignancy, is positive for cytokeratin 7 and 20 and negative for cystic disease fluid protein 15, according to the investigators (Clin. Exp. Dermatol. 2008;33:595-8). A cautionary note: Dr. Rosen said that to his knowledge these findings haven’t yet been confirmed by other groups.

He reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Even the most careful clinical pain management cannot eliminate the risk of opioid misuse in patients with a history of addiction, but good communication can help reduce the risk significantly, Dr. Sean Mackey said during a psychopharmacology conference sponsored by the Nevada Psychiatric Association.

"Some of the basic tenets of managing patients with chronic opioids are education, education, and education," said Dr. Mackey, chief of the pain management division at Stanford (Calif.) University. "It’s important to set expectations for people with chronic pain. The cure is not the goal; we’re there to help improve quality of life and get people back in control of their lives, better manage pain, and improve physical functioning."

According to best estimates from existing medical literature, the prevalence of comorbid chronic pain and opioid addiction in the United States ranges between 0.6-1.2 million people, mainly affecting young adults and the elderly. But that estimate might be conservative. A June 2011 report from the Institute of Medicine noted that chronic pain affects 116 million Americans – more than the total affected by heart disease, cancer and diabetes combined – at a cost of $560-$630 billion per year. Chronic pain "is the No. 1 reason people are out of work, hitting people often at their most productive ages, and also hitting people more and more as we advance in years," Dr. Mackey said.

In his opinion, optimal management of patients with chronic pain consists of a multidisciplinary approach "in which we bring together specialists who take care of pharmacologic aspects to pain management, physical and occupational therapy approaches, psychological/behavioral approaches, and complementary and alternative medicine approaches. It’s a team-based approach. A lot of this is dealing with body education: helping people understand what is safe for them to do and what is not safe for them to do, alleviating their fears about their body.

"We do procedural approaches as well, everything from simple trigger-point injections to spinal cord stimulation – all in the context of a functional rehabilitation approach."

Psychological approaches include giving patients time-contingent dosing of medications, "on-the-clock rather than when they are experiencing pain," said Dr. Mackey, who also directs the Stanford Systems Neuroscience and Pain Lab. "We also give positive reinforcement for healthy behaviors, negative reinforcement for unhealthy behaviors, and we get their spouse involved, because their involvement is crucial to success."

To responsibly prescribe opioids, Dr. Mackey recommends that physicians become familiar with the Federation of State Medical Boards’ Model Policy for the Treatment of Pain. He also recommends the book "Responsible Opioid Prescribing: A Physician’s Guide," by pain expert Dr. Scott M. Fishman (Waterford, Mich.: Waterford Life Sciences, 2007). This book incorporates the tenets set out in the FSMB’s model policy. "The basic tenet of this model is that pain management is a moral imperative; we should all be aware of the problems of pain management and the use of opioids may be necessary for our patients in pain," Dr. Mackey said.

The model also emphasizes that the use of opioids other than for a legitimate medical purpose "does pose a problem, that we have a responsibility to minimize the abuse and diversion with risk mitigation, [and] that physicians may deviate from recommended treatment when they have good cause. That means we’re not trying to box people in to rigid policies."

His recommended strategy for prescribing opioids in patients with a history of substance abuse starts with a careful assessment and formation of an appropriate differential diagnosis and a psychological assessment, including risk of addictive disorders. Next, have patients sign an informed consent for opioid treatment. "Our consent form has changed somewhat," Dr. Mackey said. "I’m giving patients more information about the potential for organ toxicity and the endocrine abnormalities that can occur as a consequence of opioid use, such as depression of sex hormones."

This is followed by asking patients to sign an opioid treatment agreement that informs them about your standard opioid prescribing policy, such as stating that medication will be refilled during regular office hours, Mondays through Fridays, that lost narcotic medication cannot be replaced, and that stolen narcotic medication may be replaced provided they obtain a police report and are seen in the office.

Dr. Mackey then begins patients on an appropriate trial of opioid therapy with or without adjunctive medications.

"I use the word ‘trial’ because people often think this is meant to be a long-term use of these medications when we try to make it clear right up front that use is for the short term," he explained. "I then assess and reassess their level of pain and function."

He also recommends that clinicians follow the "four As" for ongoing monitoring of pain treatment outcomes, a system developed by Steven D. Passik, Ph.D. These are analgesia (pain relief), activities of daily living (psychosocial functioning), adverse events (side effects), and aberrant drug taking (addiction-related outcomes).

"If you focus on those four As and document them, you can usually stay out of trouble when prescribing these medications," Dr. Mackey said. "Document everything in the medical record, because 95% of the problems that doctors run into with their state medical board have to do with failure to appropriately document."

Other efforts to mitigate risk include using predictive tools, urine drug testing when appropriate, and using your state’s prescription monitoring program. "Use family and friends and others to gather information to make sure that the patient is using the medication appropriately," he advised.

Potential signs of abuse and diversion include patients "who show up at the end of office hours and arrive without an appointment, or who often arrive right when your staff is trying to leave for the day," Dr. Mackey said. "They’re typically reluctant to have a thorough physical exam and don’t give you past medical records, they don’t follow up with appointments, and they have very unusual stories."

Dr. Mackey disclosed that he has received research funding from the National Institutes of Health, the Dodie and John Rosekrans Pain Research Endowment, and the Redlich Pain Research Endowment.

LAS VEGAS – Even the most careful clinical pain management cannot eliminate the risk of opioid misuse in patients with a history of addiction, but good communication can help reduce the risk significantly, Dr. Sean Mackey said during a psychopharmacology conference sponsored by the Nevada Psychiatric Association.

"Some of the basic tenets of managing patients with chronic opioids are education, education, and education," said Dr. Mackey, chief of the pain management division at Stanford (Calif.) University. "It’s important to set expectations for people with chronic pain. The cure is not the goal; we’re there to help improve quality of life and get people back in control of their lives, better manage pain, and improve physical functioning."

According to best estimates from existing medical literature, the prevalence of comorbid chronic pain and opioid addiction in the United States ranges between 0.6-1.2 million people, mainly affecting young adults and the elderly. But that estimate might be conservative. A June 2011 report from the Institute of Medicine noted that chronic pain affects 116 million Americans – more than the total affected by heart disease, cancer and diabetes combined – at a cost of $560-$630 billion per year. Chronic pain "is the No. 1 reason people are out of work, hitting people often at their most productive ages, and also hitting people more and more as we advance in years," Dr. Mackey said.

In his opinion, optimal management of patients with chronic pain consists of a multidisciplinary approach "in which we bring together specialists who take care of pharmacologic aspects to pain management, physical and occupational therapy approaches, psychological/behavioral approaches, and complementary and alternative medicine approaches. It’s a team-based approach. A lot of this is dealing with body education: helping people understand what is safe for them to do and what is not safe for them to do, alleviating their fears about their body.

"We do procedural approaches as well, everything from simple trigger-point injections to spinal cord stimulation – all in the context of a functional rehabilitation approach."

Psychological approaches include giving patients time-contingent dosing of medications, "on-the-clock rather than when they are experiencing pain," said Dr. Mackey, who also directs the Stanford Systems Neuroscience and Pain Lab. "We also give positive reinforcement for healthy behaviors, negative reinforcement for unhealthy behaviors, and we get their spouse involved, because their involvement is crucial to success."

To responsibly prescribe opioids, Dr. Mackey recommends that physicians become familiar with the Federation of State Medical Boards’ Model Policy for the Treatment of Pain. He also recommends the book "Responsible Opioid Prescribing: A Physician’s Guide," by pain expert Dr. Scott M. Fishman (Waterford, Mich.: Waterford Life Sciences, 2007). This book incorporates the tenets set out in the FSMB’s model policy. "The basic tenet of this model is that pain management is a moral imperative; we should all be aware of the problems of pain management and the use of opioids may be necessary for our patients in pain," Dr. Mackey said.

The model also emphasizes that the use of opioids other than for a legitimate medical purpose "does pose a problem, that we have a responsibility to minimize the abuse and diversion with risk mitigation, [and] that physicians may deviate from recommended treatment when they have good cause. That means we’re not trying to box people in to rigid policies."

His recommended strategy for prescribing opioids in patients with a history of substance abuse starts with a careful assessment and formation of an appropriate differential diagnosis and a psychological assessment, including risk of addictive disorders. Next, have patients sign an informed consent for opioid treatment. "Our consent form has changed somewhat," Dr. Mackey said. "I’m giving patients more information about the potential for organ toxicity and the endocrine abnormalities that can occur as a consequence of opioid use, such as depression of sex hormones."

This is followed by asking patients to sign an opioid treatment agreement that informs them about your standard opioid prescribing policy, such as stating that medication will be refilled during regular office hours, Mondays through Fridays, that lost narcotic medication cannot be replaced, and that stolen narcotic medication may be replaced provided they obtain a police report and are seen in the office.

Dr. Mackey then begins patients on an appropriate trial of opioid therapy with or without adjunctive medications.

"I use the word ‘trial’ because people often think this is meant to be a long-term use of these medications when we try to make it clear right up front that use is for the short term," he explained. "I then assess and reassess their level of pain and function."

He also recommends that clinicians follow the "four As" for ongoing monitoring of pain treatment outcomes, a system developed by Steven D. Passik, Ph.D. These are analgesia (pain relief), activities of daily living (psychosocial functioning), adverse events (side effects), and aberrant drug taking (addiction-related outcomes).

"If you focus on those four As and document them, you can usually stay out of trouble when prescribing these medications," Dr. Mackey said. "Document everything in the medical record, because 95% of the problems that doctors run into with their state medical board have to do with failure to appropriately document."

Other efforts to mitigate risk include using predictive tools, urine drug testing when appropriate, and using your state’s prescription monitoring program. "Use family and friends and others to gather information to make sure that the patient is using the medication appropriately," he advised.

Potential signs of abuse and diversion include patients "who show up at the end of office hours and arrive without an appointment, or who often arrive right when your staff is trying to leave for the day," Dr. Mackey said. "They’re typically reluctant to have a thorough physical exam and don’t give you past medical records, they don’t follow up with appointments, and they have very unusual stories."

Dr. Mackey disclosed that he has received research funding from the National Institutes of Health, the Dodie and John Rosekrans Pain Research Endowment, and the Redlich Pain Research Endowment.

LAS VEGAS – Even the most careful clinical pain management cannot eliminate the risk of opioid misuse in patients with a history of addiction, but good communication can help reduce the risk significantly, Dr. Sean Mackey said during a psychopharmacology conference sponsored by the Nevada Psychiatric Association.

"Some of the basic tenets of managing patients with chronic opioids are education, education, and education," said Dr. Mackey, chief of the pain management division at Stanford (Calif.) University. "It’s important to set expectations for people with chronic pain. The cure is not the goal; we’re there to help improve quality of life and get people back in control of their lives, better manage pain, and improve physical functioning."

According to best estimates from existing medical literature, the prevalence of comorbid chronic pain and opioid addiction in the United States ranges between 0.6-1.2 million people, mainly affecting young adults and the elderly. But that estimate might be conservative. A June 2011 report from the Institute of Medicine noted that chronic pain affects 116 million Americans – more than the total affected by heart disease, cancer and diabetes combined – at a cost of $560-$630 billion per year. Chronic pain "is the No. 1 reason people are out of work, hitting people often at their most productive ages, and also hitting people more and more as we advance in years," Dr. Mackey said.

In his opinion, optimal management of patients with chronic pain consists of a multidisciplinary approach "in which we bring together specialists who take care of pharmacologic aspects to pain management, physical and occupational therapy approaches, psychological/behavioral approaches, and complementary and alternative medicine approaches. It’s a team-based approach. A lot of this is dealing with body education: helping people understand what is safe for them to do and what is not safe for them to do, alleviating their fears about their body.

"We do procedural approaches as well, everything from simple trigger-point injections to spinal cord stimulation – all in the context of a functional rehabilitation approach."

Psychological approaches include giving patients time-contingent dosing of medications, "on-the-clock rather than when they are experiencing pain," said Dr. Mackey, who also directs the Stanford Systems Neuroscience and Pain Lab. "We also give positive reinforcement for healthy behaviors, negative reinforcement for unhealthy behaviors, and we get their spouse involved, because their involvement is crucial to success."

To responsibly prescribe opioids, Dr. Mackey recommends that physicians become familiar with the Federation of State Medical Boards’ Model Policy for the Treatment of Pain. He also recommends the book "Responsible Opioid Prescribing: A Physician’s Guide," by pain expert Dr. Scott M. Fishman (Waterford, Mich.: Waterford Life Sciences, 2007). This book incorporates the tenets set out in the FSMB’s model policy. "The basic tenet of this model is that pain management is a moral imperative; we should all be aware of the problems of pain management and the use of opioids may be necessary for our patients in pain," Dr. Mackey said.

The model also emphasizes that the use of opioids other than for a legitimate medical purpose "does pose a problem, that we have a responsibility to minimize the abuse and diversion with risk mitigation, [and] that physicians may deviate from recommended treatment when they have good cause. That means we’re not trying to box people in to rigid policies."

His recommended strategy for prescribing opioids in patients with a history of substance abuse starts with a careful assessment and formation of an appropriate differential diagnosis and a psychological assessment, including risk of addictive disorders. Next, have patients sign an informed consent for opioid treatment. "Our consent form has changed somewhat," Dr. Mackey said. "I’m giving patients more information about the potential for organ toxicity and the endocrine abnormalities that can occur as a consequence of opioid use, such as depression of sex hormones."

This is followed by asking patients to sign an opioid treatment agreement that informs them about your standard opioid prescribing policy, such as stating that medication will be refilled during regular office hours, Mondays through Fridays, that lost narcotic medication cannot be replaced, and that stolen narcotic medication may be replaced provided they obtain a police report and are seen in the office.

Dr. Mackey then begins patients on an appropriate trial of opioid therapy with or without adjunctive medications.

"I use the word ‘trial’ because people often think this is meant to be a long-term use of these medications when we try to make it clear right up front that use is for the short term," he explained. "I then assess and reassess their level of pain and function."

He also recommends that clinicians follow the "four As" for ongoing monitoring of pain treatment outcomes, a system developed by Steven D. Passik, Ph.D. These are analgesia (pain relief), activities of daily living (psychosocial functioning), adverse events (side effects), and aberrant drug taking (addiction-related outcomes).

"If you focus on those four As and document them, you can usually stay out of trouble when prescribing these medications," Dr. Mackey said. "Document everything in the medical record, because 95% of the problems that doctors run into with their state medical board have to do with failure to appropriately document."

Other efforts to mitigate risk include using predictive tools, urine drug testing when appropriate, and using your state’s prescription monitoring program. "Use family and friends and others to gather information to make sure that the patient is using the medication appropriately," he advised.

Potential signs of abuse and diversion include patients "who show up at the end of office hours and arrive without an appointment, or who often arrive right when your staff is trying to leave for the day," Dr. Mackey said. "They’re typically reluctant to have a thorough physical exam and don’t give you past medical records, they don’t follow up with appointments, and they have very unusual stories."

Dr. Mackey disclosed that he has received research funding from the National Institutes of Health, the Dodie and John Rosekrans Pain Research Endowment, and the Redlich Pain Research Endowment.

SNOWMASS, COLO. – One of the most interesting questions in all of rheumatology is this: Where does rheumatoid arthritis hang out in the body preclinically during the years following autoantibody formation but before symptomatic joint involvement?

Increasing evidence suggests that RA is smoldering in the lungs during this preclinical stage, which can last a decade or more. Indeed, bronchiole-associated lymphoid tissue may actually be the site where tolerance is broken and RA-related autoimmunity and systemic inflammation are generated, according to Dr. William F.C. Rigby, professor of medicine and professor of microbiology and immunology at Dartmouth Medical School, Hanover, N.H.

The great hope is that as this preclinical seropositive phase of RA becomes more fully understood, it will be possible to develop an autoantibody/cytokine biomarker profile in affected individuals that reliably predicts time to diagnosis. Efforts are well underway in this regard (Arthritis Rheum. 2010;62:3161-72). If such studies are validated, it will be time to launch randomized trials with the aim of preventing RA via drug therapy using methotrexate or other candidate medications while individuals are still in the preclinical stage. It’s even possible such therapy would be curative rather than suppressive, such that the medication could eventually be withdrawn.

"If methotrexate can be used to prevent the vascular complications of atherosclerosis, why can’t we use it to prevent RA? There is now [a National Institutes of Health] clinical trial proposing this. Because once the joint gets targeted, damage can happen very, very quickly. Many people have erosions on x-ray after only weeks of symptoms," the rheumatologist observed.

He credited the discovery of the existence of a lengthy preclinical seropositive phase of RA to landmark studies involving U.S. military personnel with centrally stored blood samples that were available for many years prior to their being diagnosed with RA (Ann. Rheum. Dis. 2008;67:801-7). The existence of this years-long preclinical lag time has since been confirmed in multiple other populations.

Recently, investigators at the University of Colorado at Denver, Aurora, identified the lung as an early site of autoimmune-related injury in subjects with what is being called preclinical seropositive RA (Arthritis Rheum. 2011 Dec. 19 [doi:10.1002/art.34344]).

"This is a great paper, profound in its implications," Dr. Rigby commented.

By conducting mass screenings at an annual Colorado health fair, the investigators identified a cohort of 45 subjects with preclinical RA (defined by elevated anti–cyclic citrullinated peptide antibodies and/or two or more rheumatoid factor isotypes, along with no evidence of arthritis on a 68-joint examination). Earlier work with the Armed Forces cohort had established that this serologic profile is 96% specific for RA.

All 45 subjects underwent chest CT with blinded scan readings. So did 16 seronegative healthy controls matched for age, sex, and smoking status, as well as 12 patients with early RA diagnosed less than 1 year before.

The prevalence of airways disease on CT (air trapping, bronchial wall thickening, bronchiectasis, and/or centrilobular opacities) was 77% in the autoantibody-positive preclinical RA group, compared with 31% of controls. Moreover, none of the seropositive preclinical RA subjects with CT lung abnormalities had any evidence of synovitis of their joints on MRI, indicating that RA isn’t smoldering preclinically in their joints for a long time prior to the time they show up in a rheumatologist’s office with joint symptoms. The prevalence of CT airways changes in the early RA group was similar to that in the preclinical seropositive group.

Of note, none of the subjects with preclinical RA had CT evidence of interstitial lung disease; it was all airways disease, Dr. Rigby observed.

The lung is quite plausible as the site where tolerance is broken (that is, autoantibodies against self-proteins such as cyclic citrullinated peptides are first formed), in light of the fact that smoking is a well-established environmental risk factor for RA, associated with a greater than five-fold increased risk of the rheumatologic disease in epidemiologic studies. Infectious respiratory illness could also hypothetically serve as a trigger for the breaking of tolerance, the rheumatologist said.

Some research groups are homing in on the gut or periodontal colonization by Porphyromonas gingivalis as possible key sites where tolerance is broken in individuals who will years later be diagnosed with RA. At this time, however, Dr. Rigby considers the evidence for the lung as the major player to be further along and more persuasive.

He reported having no financial conflicts.

SNOWMASS, COLO. – One of the most interesting questions in all of rheumatology is this: Where does rheumatoid arthritis hang out in the body preclinically during the years following autoantibody formation but before symptomatic joint involvement?

Increasing evidence suggests that RA is smoldering in the lungs during this preclinical stage, which can last a decade or more. Indeed, bronchiole-associated lymphoid tissue may actually be the site where tolerance is broken and RA-related autoimmunity and systemic inflammation are generated, according to Dr. William F.C. Rigby, professor of medicine and professor of microbiology and immunology at Dartmouth Medical School, Hanover, N.H.

The great hope is that as this preclinical seropositive phase of RA becomes more fully understood, it will be possible to develop an autoantibody/cytokine biomarker profile in affected individuals that reliably predicts time to diagnosis. Efforts are well underway in this regard (Arthritis Rheum. 2010;62:3161-72). If such studies are validated, it will be time to launch randomized trials with the aim of preventing RA via drug therapy using methotrexate or other candidate medications while individuals are still in the preclinical stage. It’s even possible such therapy would be curative rather than suppressive, such that the medication could eventually be withdrawn.

"If methotrexate can be used to prevent the vascular complications of atherosclerosis, why can’t we use it to prevent RA? There is now [a National Institutes of Health] clinical trial proposing this. Because once the joint gets targeted, damage can happen very, very quickly. Many people have erosions on x-ray after only weeks of symptoms," the rheumatologist observed.

He credited the discovery of the existence of a lengthy preclinical seropositive phase of RA to landmark studies involving U.S. military personnel with centrally stored blood samples that were available for many years prior to their being diagnosed with RA (Ann. Rheum. Dis. 2008;67:801-7). The existence of this years-long preclinical lag time has since been confirmed in multiple other populations.

Recently, investigators at the University of Colorado at Denver, Aurora, identified the lung as an early site of autoimmune-related injury in subjects with what is being called preclinical seropositive RA (Arthritis Rheum. 2011 Dec. 19 [doi:10.1002/art.34344]).

"This is a great paper, profound in its implications," Dr. Rigby commented.

By conducting mass screenings at an annual Colorado health fair, the investigators identified a cohort of 45 subjects with preclinical RA (defined by elevated anti–cyclic citrullinated peptide antibodies and/or two or more rheumatoid factor isotypes, along with no evidence of arthritis on a 68-joint examination). Earlier work with the Armed Forces cohort had established that this serologic profile is 96% specific for RA.

All 45 subjects underwent chest CT with blinded scan readings. So did 16 seronegative healthy controls matched for age, sex, and smoking status, as well as 12 patients with early RA diagnosed less than 1 year before.

The prevalence of airways disease on CT (air trapping, bronchial wall thickening, bronchiectasis, and/or centrilobular opacities) was 77% in the autoantibody-positive preclinical RA group, compared with 31% of controls. Moreover, none of the seropositive preclinical RA subjects with CT lung abnormalities had any evidence of synovitis of their joints on MRI, indicating that RA isn’t smoldering preclinically in their joints for a long time prior to the time they show up in a rheumatologist’s office with joint symptoms. The prevalence of CT airways changes in the early RA group was similar to that in the preclinical seropositive group.

Of note, none of the subjects with preclinical RA had CT evidence of interstitial lung disease; it was all airways disease, Dr. Rigby observed.

The lung is quite plausible as the site where tolerance is broken (that is, autoantibodies against self-proteins such as cyclic citrullinated peptides are first formed), in light of the fact that smoking is a well-established environmental risk factor for RA, associated with a greater than five-fold increased risk of the rheumatologic disease in epidemiologic studies. Infectious respiratory illness could also hypothetically serve as a trigger for the breaking of tolerance, the rheumatologist said.

Some research groups are homing in on the gut or periodontal colonization by Porphyromonas gingivalis as possible key sites where tolerance is broken in individuals who will years later be diagnosed with RA. At this time, however, Dr. Rigby considers the evidence for the lung as the major player to be further along and more persuasive.

He reported having no financial conflicts.

SNOWMASS, COLO. – One of the most interesting questions in all of rheumatology is this: Where does rheumatoid arthritis hang out in the body preclinically during the years following autoantibody formation but before symptomatic joint involvement?

Increasing evidence suggests that RA is smoldering in the lungs during this preclinical stage, which can last a decade or more. Indeed, bronchiole-associated lymphoid tissue may actually be the site where tolerance is broken and RA-related autoimmunity and systemic inflammation are generated, according to Dr. William F.C. Rigby, professor of medicine and professor of microbiology and immunology at Dartmouth Medical School, Hanover, N.H.

The great hope is that as this preclinical seropositive phase of RA becomes more fully understood, it will be possible to develop an autoantibody/cytokine biomarker profile in affected individuals that reliably predicts time to diagnosis. Efforts are well underway in this regard (Arthritis Rheum. 2010;62:3161-72). If such studies are validated, it will be time to launch randomized trials with the aim of preventing RA via drug therapy using methotrexate or other candidate medications while individuals are still in the preclinical stage. It’s even possible such therapy would be curative rather than suppressive, such that the medication could eventually be withdrawn.

"If methotrexate can be used to prevent the vascular complications of atherosclerosis, why can’t we use it to prevent RA? There is now [a National Institutes of Health] clinical trial proposing this. Because once the joint gets targeted, damage can happen very, very quickly. Many people have erosions on x-ray after only weeks of symptoms," the rheumatologist observed.

He credited the discovery of the existence of a lengthy preclinical seropositive phase of RA to landmark studies involving U.S. military personnel with centrally stored blood samples that were available for many years prior to their being diagnosed with RA (Ann. Rheum. Dis. 2008;67:801-7). The existence of this years-long preclinical lag time has since been confirmed in multiple other populations.

Recently, investigators at the University of Colorado at Denver, Aurora, identified the lung as an early site of autoimmune-related injury in subjects with what is being called preclinical seropositive RA (Arthritis Rheum. 2011 Dec. 19 [doi:10.1002/art.34344]).

"This is a great paper, profound in its implications," Dr. Rigby commented.

By conducting mass screenings at an annual Colorado health fair, the investigators identified a cohort of 45 subjects with preclinical RA (defined by elevated anti–cyclic citrullinated peptide antibodies and/or two or more rheumatoid factor isotypes, along with no evidence of arthritis on a 68-joint examination). Earlier work with the Armed Forces cohort had established that this serologic profile is 96% specific for RA.

All 45 subjects underwent chest CT with blinded scan readings. So did 16 seronegative healthy controls matched for age, sex, and smoking status, as well as 12 patients with early RA diagnosed less than 1 year before.

The prevalence of airways disease on CT (air trapping, bronchial wall thickening, bronchiectasis, and/or centrilobular opacities) was 77% in the autoantibody-positive preclinical RA group, compared with 31% of controls. Moreover, none of the seropositive preclinical RA subjects with CT lung abnormalities had any evidence of synovitis of their joints on MRI, indicating that RA isn’t smoldering preclinically in their joints for a long time prior to the time they show up in a rheumatologist’s office with joint symptoms. The prevalence of CT airways changes in the early RA group was similar to that in the preclinical seropositive group.

Of note, none of the subjects with preclinical RA had CT evidence of interstitial lung disease; it was all airways disease, Dr. Rigby observed.

The lung is quite plausible as the site where tolerance is broken (that is, autoantibodies against self-proteins such as cyclic citrullinated peptides are first formed), in light of the fact that smoking is a well-established environmental risk factor for RA, associated with a greater than five-fold increased risk of the rheumatologic disease in epidemiologic studies. Infectious respiratory illness could also hypothetically serve as a trigger for the breaking of tolerance, the rheumatologist said.

Some research groups are homing in on the gut or periodontal colonization by Porphyromonas gingivalis as possible key sites where tolerance is broken in individuals who will years later be diagnosed with RA. At this time, however, Dr. Rigby considers the evidence for the lung as the major player to be further along and more persuasive.

He reported having no financial conflicts.

SNOWMASS, COLO. – Some of the most widely accepted core concepts regarding the pathogenesis of psoriatic arthritis are probably incorrect.

Conventional wisdom holds that psoriatic arthritis – like rheumatoid arthritis – is an autoimmune disease, that the mechanisms underlying the two inflammatory diseases run parallel, and that the therapeutic response of psoriatic arthritis (PsA) to a variety of agents is similar to that in RA. All three of these paradigms are likely headed for the scrap heap, according to Dr. Christopher T. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.).

Here’s why:

• Autoimmunity. RA is an autoantibody-mediated disease involving MHC (major histocompatibility complex) class II. In contrast, no autoantibodies have been linked to PsA, an MHC class I–related disorder.

Moreover, the foci of joint inflammation are quite different in the two diseases. In RA, the primary site of inflammation is synovial tissue, whereas in PsA the targets of inflammation – including the bone marrow and entheses as well as synovium – are strikingly heterogeneous.

The alterations in bone are very different in RA and PsA. The bone remodeling characteristic of RA is a catabolic process marked by focal bony erosions and osteopenia. In contrast, patients with PsA can have bone destruction and bone formation going on simultaneously in the same hand.

The extra-articular manifestations of the two diseases are different as well. RA is associated with vasculitis, Sjögren’s syndrome, and nodules. PsA has psoriasis, uveitis, and bowel inflammation as its chief extra-articular manifestations. Indeed, acute or chronic bowel inflammation has been detected in 15%-30% of PsA patients without abdominal symptoms; it’s most common in patients with axial involvement.

"I have in my own practice three patients whose psoriatic arthritis has been effectively controlled with etanercept. Then I get a phone call that they’re having fevers, they’re not feeling well, losing weight. A work-up for infection ensues, and it turns out after a couple of weeks that the bowel symptoms are predominating and these patients have developed florid Crohn’s disease. In talking to rheumatologists around the country, this is something others have seen as well. It’s an intriguing phenomenon: You can control one arm of inflammation in the joints and the skin, but the bowel seems to break through by mechanisms that are not well understood," Dr. Ritchlin said.

PsA is also distinct from RA in terms of potentially modifiable environmental risk factors. Epidemiologic studies have linked an increased risk of PsA to more-severe psoriatic skin disease, nail dystrophy, moving to a new home, trauma leading to medical care, vaccination for rubella, and obesity (Arch. Dermatol. 2010;146:785-8). The link with rubella vaccination definitely needs confirmation before gaining acceptance. However, the association between obesity and increased risk of PsA has been validated, Dr. Ritchlin observed.

"My view and that of many others in the field is that perhaps psoriatic arthritis is not a typical autoimmune disease. But rather, it involves a more innate immune response that has yet to be fully understood," the rheumatologist said.

• Divergent cellular pathobiology. The T cell clearly plays a crucial role in the pathogenesis of RA. But there is little evidence to suggest that T lymphocytes are key cells in the pathobiology of psoriatic arthritis. Instead, the monocyte appears to be the most important cell in that disease, Dr. Ritchlin noted.

Increased levels of circulating osteoclast precursor cells are a feature of both psoriatic arthritis and psoriasis but not RA.

Interleukin-17’s exact role in the immunopathology of psoriatic arthritis isn’t yet understood. Three major clinical trials are looking at the therapeutic impact of blocking IL-17 in psoriatic arthritis, including two recently completed phase III studies of ustekinumab (Stelara); the first, conducted in TNF (tumor necrosis factor) inhibitor–naive subjects, will be presented at EULAR in Berlin in June, with data from the other two studies to come in the following half-year. One of the trials involves a monoclonal antibody to the IL-17 receptor; this agent has shown spectacular efficacy in psoriasis but is not effective in RA, so its impact in PsA will be of particular interest.

"I think having the data from these trials will make for a major advance in helping us to understand the pathogenic pathways," Dr. Ritchlin said.

• Treatment response. There is no evidence that the conventional DMARDs (disease-modifying antirheumatic drugs) that have well-established benefit in RA also slow radiographic progression of PsA. Moreover, recent studies of abatacept and rituximab (biologic agents that are highly effective in RA) failed to show benefit in PsA.

Methotrexate is widely prescribed for the treatment of psoriatic arthritis, yet its role remains controversial and unsupported by persuasive evidence. The British MIPA (Methotrexate in Psoriatic Arthritis) trial concluded that methotrexate wasn’t superior to placebo, and hence can’t be considered a DMARD in PsA (Rheumatology [Oxford] 2012 Feb. 17 [epub ahead of print]). Design limitations rendered MIPA a less-than-definitive study; however, it’s unlikely any further placebo-controlled trials of methotrexate in PsA will be carried out, in Dr. Ritchlin’s view.

"The role of methotrexate remains to be determined, but it’s not looking good at this point," he observed.

Rheumatologists with RA patients on methotrexate typically monitor them for hepatic fibrosis via liver function tests rather than liver biopsy. However, Dr. Ritchlin believes that more-invasive monitoring is warranted in psoriatic arthritis patients with type 2 diabetes, obesity, or both, as these have been shown to be risk factors for accelerated liver fibrosis in psoriasis patients on methotrexate (J. Hepatol. 2007;46:1111-8).

"When I have a patient with psoriatic arthritis, and we’re going to use methotrexate, and they have type 2 diabetes or are obese, I tell them about that study, in which investigators did biopsies and showed that these two risk factors, alone or together, identify rapid progressors in terms of fibrosis. I tell those patients they should have liver biopsies at 2-g intervals. And most of those patients will elect to use another therapy when I tell them that. But I think it’s important to enlighten them" on those data, Dr. Ritchlin said.

On the therapeutic horizon – in addition to the studies of IL-17 inhibition – is a phase III clinical trial of apremilast in the treatment of PsA, which has been completed and submitted for publication following a successful placebo-controlled, phase II study of the investigational novel oral phosphodiesterase-4 inhibitor.

"This drug has a very low side-effect profile," Dr. Ritchlin commented.

Promising new targets in psoriatic arthritis that have yet to be explored include RANKL (receptor-activated nuclear factor–kappaB ligand) and the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway.

The TNF inhibitors are the best established agents today for treatment of PsA. In phase III trials, all of the TNF inhibitors showed similar efficacy for the joint disease, whereas the skin response was better with the antibody agents.

Dr. Ritchlin said he is asked all the time about what to do for PsA patients who are TNF-inhibitor nonresponders. His strategy is first to focus on treating the site of the flare; for example, if it’s a skin flare, he works with a dermatologist, who may address the skin lesions with phototherapy or topical agents.

Next, he considers switching to a different TNF inhibitor or adding or switching a conventional DMARD. "A switch to leflunomide (Arava) can be very effective in this population, especially for joint flares," the rheumatologist continued.

If the patient’s response is still inadequate, Dr. Ritchlin switches from a TNF inhibitor to ustekinumab on the strength of a favorable phase II study (Lancet 2009;373:633-40).

Dr. Ritchlin reported serving as a consultant to Abbott, Amgen, Centocor, UCB, Wyeth, Genentech, and Targacept, as well as receiving research funding from multiple sources.

SNOWMASS, COLO. – Some of the most widely accepted core concepts regarding the pathogenesis of psoriatic arthritis are probably incorrect.

Conventional wisdom holds that psoriatic arthritis – like rheumatoid arthritis – is an autoimmune disease, that the mechanisms underlying the two inflammatory diseases run parallel, and that the therapeutic response of psoriatic arthritis (PsA) to a variety of agents is similar to that in RA. All three of these paradigms are likely headed for the scrap heap, according to Dr. Christopher T. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.).

Here’s why:

• Autoimmunity. RA is an autoantibody-mediated disease involving MHC (major histocompatibility complex) class II. In contrast, no autoantibodies have been linked to PsA, an MHC class I–related disorder.

Moreover, the foci of joint inflammation are quite different in the two diseases. In RA, the primary site of inflammation is synovial tissue, whereas in PsA the targets of inflammation – including the bone marrow and entheses as well as synovium – are strikingly heterogeneous.

The alterations in bone are very different in RA and PsA. The bone remodeling characteristic of RA is a catabolic process marked by focal bony erosions and osteopenia. In contrast, patients with PsA can have bone destruction and bone formation going on simultaneously in the same hand.

The extra-articular manifestations of the two diseases are different as well. RA is associated with vasculitis, Sjögren’s syndrome, and nodules. PsA has psoriasis, uveitis, and bowel inflammation as its chief extra-articular manifestations. Indeed, acute or chronic bowel inflammation has been detected in 15%-30% of PsA patients without abdominal symptoms; it’s most common in patients with axial involvement.

"I have in my own practice three patients whose psoriatic arthritis has been effectively controlled with etanercept. Then I get a phone call that they’re having fevers, they’re not feeling well, losing weight. A work-up for infection ensues, and it turns out after a couple of weeks that the bowel symptoms are predominating and these patients have developed florid Crohn’s disease. In talking to rheumatologists around the country, this is something others have seen as well. It’s an intriguing phenomenon: You can control one arm of inflammation in the joints and the skin, but the bowel seems to break through by mechanisms that are not well understood," Dr. Ritchlin said.

PsA is also distinct from RA in terms of potentially modifiable environmental risk factors. Epidemiologic studies have linked an increased risk of PsA to more-severe psoriatic skin disease, nail dystrophy, moving to a new home, trauma leading to medical care, vaccination for rubella, and obesity (Arch. Dermatol. 2010;146:785-8). The link with rubella vaccination definitely needs confirmation before gaining acceptance. However, the association between obesity and increased risk of PsA has been validated, Dr. Ritchlin observed.

"My view and that of many others in the field is that perhaps psoriatic arthritis is not a typical autoimmune disease. But rather, it involves a more innate immune response that has yet to be fully understood," the rheumatologist said.

• Divergent cellular pathobiology. The T cell clearly plays a crucial role in the pathogenesis of RA. But there is little evidence to suggest that T lymphocytes are key cells in the pathobiology of psoriatic arthritis. Instead, the monocyte appears to be the most important cell in that disease, Dr. Ritchlin noted.

Increased levels of circulating osteoclast precursor cells are a feature of both psoriatic arthritis and psoriasis but not RA.

Interleukin-17’s exact role in the immunopathology of psoriatic arthritis isn’t yet understood. Three major clinical trials are looking at the therapeutic impact of blocking IL-17 in psoriatic arthritis, including two recently completed phase III studies of ustekinumab (Stelara); the first, conducted in TNF (tumor necrosis factor) inhibitor–naive subjects, will be presented at EULAR in Berlin in June, with data from the other two studies to come in the following half-year. One of the trials involves a monoclonal antibody to the IL-17 receptor; this agent has shown spectacular efficacy in psoriasis but is not effective in RA, so its impact in PsA will be of particular interest.

"I think having the data from these trials will make for a major advance in helping us to understand the pathogenic pathways," Dr. Ritchlin said.

• Treatment response. There is no evidence that the conventional DMARDs (disease-modifying antirheumatic drugs) that have well-established benefit in RA also slow radiographic progression of PsA. Moreover, recent studies of abatacept and rituximab (biologic agents that are highly effective in RA) failed to show benefit in PsA.

Methotrexate is widely prescribed for the treatment of psoriatic arthritis, yet its role remains controversial and unsupported by persuasive evidence. The British MIPA (Methotrexate in Psoriatic Arthritis) trial concluded that methotrexate wasn’t superior to placebo, and hence can’t be considered a DMARD in PsA (Rheumatology [Oxford] 2012 Feb. 17 [epub ahead of print]). Design limitations rendered MIPA a less-than-definitive study; however, it’s unlikely any further placebo-controlled trials of methotrexate in PsA will be carried out, in Dr. Ritchlin’s view.

"The role of methotrexate remains to be determined, but it’s not looking good at this point," he observed.

Rheumatologists with RA patients on methotrexate typically monitor them for hepatic fibrosis via liver function tests rather than liver biopsy. However, Dr. Ritchlin believes that more-invasive monitoring is warranted in psoriatic arthritis patients with type 2 diabetes, obesity, or both, as these have been shown to be risk factors for accelerated liver fibrosis in psoriasis patients on methotrexate (J. Hepatol. 2007;46:1111-8).

"When I have a patient with psoriatic arthritis, and we’re going to use methotrexate, and they have type 2 diabetes or are obese, I tell them about that study, in which investigators did biopsies and showed that these two risk factors, alone or together, identify rapid progressors in terms of fibrosis. I tell those patients they should have liver biopsies at 2-g intervals. And most of those patients will elect to use another therapy when I tell them that. But I think it’s important to enlighten them" on those data, Dr. Ritchlin said.

On the therapeutic horizon – in addition to the studies of IL-17 inhibition – is a phase III clinical trial of apremilast in the treatment of PsA, which has been completed and submitted for publication following a successful placebo-controlled, phase II study of the investigational novel oral phosphodiesterase-4 inhibitor.

"This drug has a very low side-effect profile," Dr. Ritchlin commented.

Promising new targets in psoriatic arthritis that have yet to be explored include RANKL (receptor-activated nuclear factor–kappaB ligand) and the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway.

The TNF inhibitors are the best established agents today for treatment of PsA. In phase III trials, all of the TNF inhibitors showed similar efficacy for the joint disease, whereas the skin response was better with the antibody agents.

Dr. Ritchlin said he is asked all the time about what to do for PsA patients who are TNF-inhibitor nonresponders. His strategy is first to focus on treating the site of the flare; for example, if it’s a skin flare, he works with a dermatologist, who may address the skin lesions with phototherapy or topical agents.

Next, he considers switching to a different TNF inhibitor or adding or switching a conventional DMARD. "A switch to leflunomide (Arava) can be very effective in this population, especially for joint flares," the rheumatologist continued.

If the patient’s response is still inadequate, Dr. Ritchlin switches from a TNF inhibitor to ustekinumab on the strength of a favorable phase II study (Lancet 2009;373:633-40).

Dr. Ritchlin reported serving as a consultant to Abbott, Amgen, Centocor, UCB, Wyeth, Genentech, and Targacept, as well as receiving research funding from multiple sources.

SNOWMASS, COLO. – Some of the most widely accepted core concepts regarding the pathogenesis of psoriatic arthritis are probably incorrect.

Conventional wisdom holds that psoriatic arthritis – like rheumatoid arthritis – is an autoimmune disease, that the mechanisms underlying the two inflammatory diseases run parallel, and that the therapeutic response of psoriatic arthritis (PsA) to a variety of agents is similar to that in RA. All three of these paradigms are likely headed for the scrap heap, according to Dr. Christopher T. Ritchlin, professor of medicine and director of the translational immunology research center at the University of Rochester (N.Y.).

Here’s why:

• Autoimmunity. RA is an autoantibody-mediated disease involving MHC (major histocompatibility complex) class II. In contrast, no autoantibodies have been linked to PsA, an MHC class I–related disorder.

Moreover, the foci of joint inflammation are quite different in the two diseases. In RA, the primary site of inflammation is synovial tissue, whereas in PsA the targets of inflammation – including the bone marrow and entheses as well as synovium – are strikingly heterogeneous.

The alterations in bone are very different in RA and PsA. The bone remodeling characteristic of RA is a catabolic process marked by focal bony erosions and osteopenia. In contrast, patients with PsA can have bone destruction and bone formation going on simultaneously in the same hand.

The extra-articular manifestations of the two diseases are different as well. RA is associated with vasculitis, Sjögren’s syndrome, and nodules. PsA has psoriasis, uveitis, and bowel inflammation as its chief extra-articular manifestations. Indeed, acute or chronic bowel inflammation has been detected in 15%-30% of PsA patients without abdominal symptoms; it’s most common in patients with axial involvement.

"I have in my own practice three patients whose psoriatic arthritis has been effectively controlled with etanercept. Then I get a phone call that they’re having fevers, they’re not feeling well, losing weight. A work-up for infection ensues, and it turns out after a couple of weeks that the bowel symptoms are predominating and these patients have developed florid Crohn’s disease. In talking to rheumatologists around the country, this is something others have seen as well. It’s an intriguing phenomenon: You can control one arm of inflammation in the joints and the skin, but the bowel seems to break through by mechanisms that are not well understood," Dr. Ritchlin said.

PsA is also distinct from RA in terms of potentially modifiable environmental risk factors. Epidemiologic studies have linked an increased risk of PsA to more-severe psoriatic skin disease, nail dystrophy, moving to a new home, trauma leading to medical care, vaccination for rubella, and obesity (Arch. Dermatol. 2010;146:785-8). The link with rubella vaccination definitely needs confirmation before gaining acceptance. However, the association between obesity and increased risk of PsA has been validated, Dr. Ritchlin observed.

"My view and that of many others in the field is that perhaps psoriatic arthritis is not a typical autoimmune disease. But rather, it involves a more innate immune response that has yet to be fully understood," the rheumatologist said.

• Divergent cellular pathobiology. The T cell clearly plays a crucial role in the pathogenesis of RA. But there is little evidence to suggest that T lymphocytes are key cells in the pathobiology of psoriatic arthritis. Instead, the monocyte appears to be the most important cell in that disease, Dr. Ritchlin noted.

Increased levels of circulating osteoclast precursor cells are a feature of both psoriatic arthritis and psoriasis but not RA.

Interleukin-17’s exact role in the immunopathology of psoriatic arthritis isn’t yet understood. Three major clinical trials are looking at the therapeutic impact of blocking IL-17 in psoriatic arthritis, including two recently completed phase III studies of ustekinumab (Stelara); the first, conducted in TNF (tumor necrosis factor) inhibitor–naive subjects, will be presented at EULAR in Berlin in June, with data from the other two studies to come in the following half-year. One of the trials involves a monoclonal antibody to the IL-17 receptor; this agent has shown spectacular efficacy in psoriasis but is not effective in RA, so its impact in PsA will be of particular interest.

"I think having the data from these trials will make for a major advance in helping us to understand the pathogenic pathways," Dr. Ritchlin said.

• Treatment response. There is no evidence that the conventional DMARDs (disease-modifying antirheumatic drugs) that have well-established benefit in RA also slow radiographic progression of PsA. Moreover, recent studies of abatacept and rituximab (biologic agents that are highly effective in RA) failed to show benefit in PsA.

Methotrexate is widely prescribed for the treatment of psoriatic arthritis, yet its role remains controversial and unsupported by persuasive evidence. The British MIPA (Methotrexate in Psoriatic Arthritis) trial concluded that methotrexate wasn’t superior to placebo, and hence can’t be considered a DMARD in PsA (Rheumatology [Oxford] 2012 Feb. 17 [epub ahead of print]). Design limitations rendered MIPA a less-than-definitive study; however, it’s unlikely any further placebo-controlled trials of methotrexate in PsA will be carried out, in Dr. Ritchlin’s view.

"The role of methotrexate remains to be determined, but it’s not looking good at this point," he observed.

Rheumatologists with RA patients on methotrexate typically monitor them for hepatic fibrosis via liver function tests rather than liver biopsy. However, Dr. Ritchlin believes that more-invasive monitoring is warranted in psoriatic arthritis patients with type 2 diabetes, obesity, or both, as these have been shown to be risk factors for accelerated liver fibrosis in psoriasis patients on methotrexate (J. Hepatol. 2007;46:1111-8).

"When I have a patient with psoriatic arthritis, and we’re going to use methotrexate, and they have type 2 diabetes or are obese, I tell them about that study, in which investigators did biopsies and showed that these two risk factors, alone or together, identify rapid progressors in terms of fibrosis. I tell those patients they should have liver biopsies at 2-g intervals. And most of those patients will elect to use another therapy when I tell them that. But I think it’s important to enlighten them" on those data, Dr. Ritchlin said.

On the therapeutic horizon – in addition to the studies of IL-17 inhibition – is a phase III clinical trial of apremilast in the treatment of PsA, which has been completed and submitted for publication following a successful placebo-controlled, phase II study of the investigational novel oral phosphodiesterase-4 inhibitor.

"This drug has a very low side-effect profile," Dr. Ritchlin commented.

Promising new targets in psoriatic arthritis that have yet to be explored include RANKL (receptor-activated nuclear factor–kappaB ligand) and the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway.

The TNF inhibitors are the best established agents today for treatment of PsA. In phase III trials, all of the TNF inhibitors showed similar efficacy for the joint disease, whereas the skin response was better with the antibody agents.

Dr. Ritchlin said he is asked all the time about what to do for PsA patients who are TNF-inhibitor nonresponders. His strategy is first to focus on treating the site of the flare; for example, if it’s a skin flare, he works with a dermatologist, who may address the skin lesions with phototherapy or topical agents.

Next, he considers switching to a different TNF inhibitor or adding or switching a conventional DMARD. "A switch to leflunomide (Arava) can be very effective in this population, especially for joint flares," the rheumatologist continued.

If the patient’s response is still inadequate, Dr. Ritchlin switches from a TNF inhibitor to ustekinumab on the strength of a favorable phase II study (Lancet 2009;373:633-40).

Dr. Ritchlin reported serving as a consultant to Abbott, Amgen, Centocor, UCB, Wyeth, Genentech, and Targacept, as well as receiving research funding from multiple sources.

Rheumatoid arthritis patients had a 40% increased risk of atrial fibrillation and a 30% increased risk of stroke compared to the general population, based on data from a national cohort study in Denmark.

Previous studies have shown an association between rheumatoid arthritis (RA) and increased risk of myocardial infarction, but data on the risk of stroke have been inconsistent, said Dr. Jesper Lindhardsen, a research fellow in the department of cardiology at Gentofte Hospital in Hellerup, Denmark.

The findings were published online March 8 in the British Medical Journal (BMJ 2012 March 8 [doi: 10.1136/bmj.e1257]).

Dr. Lindhardsen and colleagues reviewed data from a national registry that included all Danish individuals older than 15 years of age as of Jan. 1, 1997. The study cohort included 4.3 million individuals. Of these, 18,247 had RA. During a follow-up period of up to 13 years, a total of 156,484 individuals, including 774 RA patients, were diagnosed with atrial fibrillation, and 165,343 individuals, including 718 RA patients, had a stroke.

The incidence of atrial fibrillation (a modifiable risk factor for stroke) was 8.2 events per 1,000 person-years in RA patients vs. 6 events per 1,000 person years in the general population. Women were at slightly increased risk, compared with men, and the risk was significantly higher in the youngest age groups. "The absolute risk attributable to rheumatoid arthritis ranged from 25% in the oldest to 70% in the youngest age group," the researchers noted.

The incidence of stroke was 7.6 per 1,000 person-years among RA patients vs. 5.7 per 1,000 person-years in the general population. As with atrial fibrillation, the relative risk for stroke in RA patients was highest in the younger age groups.

"Nonetheless, the absolute differences in rates of atrial fibrillation and stroke between people with and without rheumatoid arthritis were highest in the oldest patients," the researchers said.

The study is the first known to examine the incidence of atrial fibrillation in a large population of RA patients. The results were limited by the use of a national registry, which missed patients not seen in clinics or treated with antirheumatic drugs during the study period.

However, the findings correspond to one new case of atrial fibrillation per 12 RA patients followed for 10 years after their diagnoses, the researchers said. Therefore, the researchers recommended that clinical care of RA patients include screening for atrial fibrillation.

"This study also underlines the importance of rigorous control of inflammation with disease modifying antirheumatic drugs, not only for the management of joint symptoms but also to reduce the need for drugs with potential adverse cardiovascular effects and, ultimately, to diminish the inflammation driven atherothrombotic process," they emphasized.

The findings are a continuation of data presented by Dr. Lindhardsen at the European Society of Cardiology meeting in 2010 in Stockholm.

Dr. Lindhardsen said he had no financial conflicts to disclose.

Rheumatoid arthritis patients had a 40% increased risk of atrial fibrillation and a 30% increased risk of stroke compared to the general population, based on data from a national cohort study in Denmark.

Previous studies have shown an association between rheumatoid arthritis (RA) and increased risk of myocardial infarction, but data on the risk of stroke have been inconsistent, said Dr. Jesper Lindhardsen, a research fellow in the department of cardiology at Gentofte Hospital in Hellerup, Denmark.

The findings were published online March 8 in the British Medical Journal (BMJ 2012 March 8 [doi: 10.1136/bmj.e1257]).

Dr. Lindhardsen and colleagues reviewed data from a national registry that included all Danish individuals older than 15 years of age as of Jan. 1, 1997. The study cohort included 4.3 million individuals. Of these, 18,247 had RA. During a follow-up period of up to 13 years, a total of 156,484 individuals, including 774 RA patients, were diagnosed with atrial fibrillation, and 165,343 individuals, including 718 RA patients, had a stroke.

The incidence of atrial fibrillation (a modifiable risk factor for stroke) was 8.2 events per 1,000 person-years in RA patients vs. 6 events per 1,000 person years in the general population. Women were at slightly increased risk, compared with men, and the risk was significantly higher in the youngest age groups. "The absolute risk attributable to rheumatoid arthritis ranged from 25% in the oldest to 70% in the youngest age group," the researchers noted.

The incidence of stroke was 7.6 per 1,000 person-years among RA patients vs. 5.7 per 1,000 person-years in the general population. As with atrial fibrillation, the relative risk for stroke in RA patients was highest in the younger age groups.

"Nonetheless, the absolute differences in rates of atrial fibrillation and stroke between people with and without rheumatoid arthritis were highest in the oldest patients," the researchers said.

The study is the first known to examine the incidence of atrial fibrillation in a large population of RA patients. The results were limited by the use of a national registry, which missed patients not seen in clinics or treated with antirheumatic drugs during the study period.

However, the findings correspond to one new case of atrial fibrillation per 12 RA patients followed for 10 years after their diagnoses, the researchers said. Therefore, the researchers recommended that clinical care of RA patients include screening for atrial fibrillation.

"This study also underlines the importance of rigorous control of inflammation with disease modifying antirheumatic drugs, not only for the management of joint symptoms but also to reduce the need for drugs with potential adverse cardiovascular effects and, ultimately, to diminish the inflammation driven atherothrombotic process," they emphasized.

The findings are a continuation of data presented by Dr. Lindhardsen at the European Society of Cardiology meeting in 2010 in Stockholm.

Dr. Lindhardsen said he had no financial conflicts to disclose.

Rheumatoid arthritis patients had a 40% increased risk of atrial fibrillation and a 30% increased risk of stroke compared to the general population, based on data from a national cohort study in Denmark.

Previous studies have shown an association between rheumatoid arthritis (RA) and increased risk of myocardial infarction, but data on the risk of stroke have been inconsistent, said Dr. Jesper Lindhardsen, a research fellow in the department of cardiology at Gentofte Hospital in Hellerup, Denmark.

The findings were published online March 8 in the British Medical Journal (BMJ 2012 March 8 [doi: 10.1136/bmj.e1257]).

Dr. Lindhardsen and colleagues reviewed data from a national registry that included all Danish individuals older than 15 years of age as of Jan. 1, 1997. The study cohort included 4.3 million individuals. Of these, 18,247 had RA. During a follow-up period of up to 13 years, a total of 156,484 individuals, including 774 RA patients, were diagnosed with atrial fibrillation, and 165,343 individuals, including 718 RA patients, had a stroke.

The incidence of atrial fibrillation (a modifiable risk factor for stroke) was 8.2 events per 1,000 person-years in RA patients vs. 6 events per 1,000 person years in the general population. Women were at slightly increased risk, compared with men, and the risk was significantly higher in the youngest age groups. "The absolute risk attributable to rheumatoid arthritis ranged from 25% in the oldest to 70% in the youngest age group," the researchers noted.

The incidence of stroke was 7.6 per 1,000 person-years among RA patients vs. 5.7 per 1,000 person-years in the general population. As with atrial fibrillation, the relative risk for stroke in RA patients was highest in the younger age groups.

"Nonetheless, the absolute differences in rates of atrial fibrillation and stroke between people with and without rheumatoid arthritis were highest in the oldest patients," the researchers said.

The study is the first known to examine the incidence of atrial fibrillation in a large population of RA patients. The results were limited by the use of a national registry, which missed patients not seen in clinics or treated with antirheumatic drugs during the study period.

However, the findings correspond to one new case of atrial fibrillation per 12 RA patients followed for 10 years after their diagnoses, the researchers said. Therefore, the researchers recommended that clinical care of RA patients include screening for atrial fibrillation.

"This study also underlines the importance of rigorous control of inflammation with disease modifying antirheumatic drugs, not only for the management of joint symptoms but also to reduce the need for drugs with potential adverse cardiovascular effects and, ultimately, to diminish the inflammation driven atherothrombotic process," they emphasized.

The findings are a continuation of data presented by Dr. Lindhardsen at the European Society of Cardiology meeting in 2010 in Stockholm.

Dr. Lindhardsen said he had no financial conflicts to disclose.

SNOWMASS, COLO. – It’s now confirmed: obesity in psoriasis patients is a major independent risk factor for psoriatic arthritis.

This finding is actually good news. It opens the door to the potential prevention of psoriatic arthritis (PsA) through weight loss. Many psoriasis patients are obese and have the metabolic syndrome. And since a decade goes by on average between onset of psoriasis and development of joint disease, the prospect of a lowered risk of PsA could be a powerful motivator for heavy psoriasis patients to shed pounds, according to Dr. Christopher T. Ritchlin, professor of medicine and director of the Translational Immunology Research Center at the University of Rochester (N.Y.).

That being said, it must be noted that there is as yet no solid evidence that weight loss actually lowers a psoriasis patient’s risk of developing PsA. A few studies are looking into whether weight loss makes a difference, but these investigations have been hampered – no surprise – by difficulty in getting patients to achieve and maintain significant weight loss, the rheumatologist noted.

Obesity is an established risk factor for psoriasis. The possibility that obesity among psoriasis patients is also a risk factor for PsA was raised in a study by investigators with the Utah Psoriasis Initiative, who found that self-reported increased body mass index (BMI) at age 18 years was associated with greater risk of PsA (Arch. Dermatol. 2010;146:721-6).

The Utah finding that greater obesity contributes to an increased risk of PsA has since been confirmed in an impressively large cohort study using data from The Health Improvement Network (THIN), a general practice electronic medical records database that includes more than 7.5 million U.K. patients. THIN is a newer database that is separate from the renowned U.K. General Practice Research Database, which has generated key findings on psoriasis as an independent cardiovascular risk factor.

At last year’s annual meeting of the American College of Rheumatology, THIN investigators reported that among 75,395 THIN enrollees with psoriasis followed for a mean of 5 years, 976 developed PsA.

The incidence of PsA was 23.09 cases/10,000 person-years in subjects whose first BMI measurement after diagnosis of psoriasis showed a BMI of less than 25 kg/m². The incidence climbed stepwise with increasing BMI. Among subjects with a BMI of 25-29.9 kg/m², the incidence was 25.37 cases/10,000 person-years. For those with a BMI of 30-34.9 kg/m², it was 29.33 cases/10,000, while in those with a BMI of 35 kg/m² or more the incidence of PsA was 38.04 cases/10,000.

In a multivariate analysis adjusted for potential confounders, the risk of developing PsA was 12% higher in subjects with a BMI of 25-29.9 than in those with a BMI below 25 kg/m², 46% greater in those with a BMI of 30-34.9 kg/m², and 75% higher in subjects with a BMI of 35 kg/m² or more.

Dr. Ritchlin noted that a separate THIN analysis recently demonstrated that the prevalence of PsA climbs dramatically with more extensive psoriasis independent of other risk factors. This analysis included 4,539 middle-aged psoriasis patients. The overall prevalence of PsA was 8.4%. The lifetime prevalence of PsA was 4.5% among patients whose psoriasis involved 2% or less of their body surface area (BSA), 9.3% among those with 3%-10% BSA involvement, and 22.1% in subjects whose psoriasis affected more than 10% of their BSA.

"I know you’re all going to say, ‘Wait a minute, I have patients who have almost no psoriasis and yet have psoriatic arthritis.’ That’s very true. I have the same experience. But if you look at population-based data, the more severe your psoriasis, the more likely you are to get psoriatic arthritis," the rheumatologist declared.

He reported serving as a consultant to Abbott, Amgen, Centocor, Genentech, Targacept, UCB, and Wyeth and receiving research funding from multiple sources.

SNOWMASS, COLO. – It’s now confirmed: obesity in psoriasis patients is a major independent risk factor for psoriatic arthritis.

This finding is actually good news. It opens the door to the potential prevention of psoriatic arthritis (PsA) through weight loss. Many psoriasis patients are obese and have the metabolic syndrome. And since a decade goes by on average between onset of psoriasis and development of joint disease, the prospect of a lowered risk of PsA could be a powerful motivator for heavy psoriasis patients to shed pounds, according to Dr. Christopher T. Ritchlin, professor of medicine and director of the Translational Immunology Research Center at the University of Rochester (N.Y.).

That being said, it must be noted that there is as yet no solid evidence that weight loss actually lowers a psoriasis patient’s risk of developing PsA. A few studies are looking into whether weight loss makes a difference, but these investigations have been hampered – no surprise – by difficulty in getting patients to achieve and maintain significant weight loss, the rheumatologist noted.

Obesity is an established risk factor for psoriasis. The possibility that obesity among psoriasis patients is also a risk factor for PsA was raised in a study by investigators with the Utah Psoriasis Initiative, who found that self-reported increased body mass index (BMI) at age 18 years was associated with greater risk of PsA (Arch. Dermatol. 2010;146:721-6).

The Utah finding that greater obesity contributes to an increased risk of PsA has since been confirmed in an impressively large cohort study using data from The Health Improvement Network (THIN), a general practice electronic medical records database that includes more than 7.5 million U.K. patients. THIN is a newer database that is separate from the renowned U.K. General Practice Research Database, which has generated key findings on psoriasis as an independent cardiovascular risk factor.

At last year’s annual meeting of the American College of Rheumatology, THIN investigators reported that among 75,395 THIN enrollees with psoriasis followed for a mean of 5 years, 976 developed PsA.

The incidence of PsA was 23.09 cases/10,000 person-years in subjects whose first BMI measurement after diagnosis of psoriasis showed a BMI of less than 25 kg/m². The incidence climbed stepwise with increasing BMI. Among subjects with a BMI of 25-29.9 kg/m², the incidence was 25.37 cases/10,000 person-years. For those with a BMI of 30-34.9 kg/m², it was 29.33 cases/10,000, while in those with a BMI of 35 kg/m² or more the incidence of PsA was 38.04 cases/10,000.

In a multivariate analysis adjusted for potential confounders, the risk of developing PsA was 12% higher in subjects with a BMI of 25-29.9 than in those with a BMI below 25 kg/m², 46% greater in those with a BMI of 30-34.9 kg/m², and 75% higher in subjects with a BMI of 35 kg/m² or more.

Dr. Ritchlin noted that a separate THIN analysis recently demonstrated that the prevalence of PsA climbs dramatically with more extensive psoriasis independent of other risk factors. This analysis included 4,539 middle-aged psoriasis patients. The overall prevalence of PsA was 8.4%. The lifetime prevalence of PsA was 4.5% among patients whose psoriasis involved 2% or less of their body surface area (BSA), 9.3% among those with 3%-10% BSA involvement, and 22.1% in subjects whose psoriasis affected more than 10% of their BSA.

"I know you’re all going to say, ‘Wait a minute, I have patients who have almost no psoriasis and yet have psoriatic arthritis.’ That’s very true. I have the same experience. But if you look at population-based data, the more severe your psoriasis, the more likely you are to get psoriatic arthritis," the rheumatologist declared.

He reported serving as a consultant to Abbott, Amgen, Centocor, Genentech, Targacept, UCB, and Wyeth and receiving research funding from multiple sources.

SNOWMASS, COLO. – It’s now confirmed: obesity in psoriasis patients is a major independent risk factor for psoriatic arthritis.

This finding is actually good news. It opens the door to the potential prevention of psoriatic arthritis (PsA) through weight loss. Many psoriasis patients are obese and have the metabolic syndrome. And since a decade goes by on average between onset of psoriasis and development of joint disease, the prospect of a lowered risk of PsA could be a powerful motivator for heavy psoriasis patients to shed pounds, according to Dr. Christopher T. Ritchlin, professor of medicine and director of the Translational Immunology Research Center at the University of Rochester (N.Y.).

That being said, it must be noted that there is as yet no solid evidence that weight loss actually lowers a psoriasis patient’s risk of developing PsA. A few studies are looking into whether weight loss makes a difference, but these investigations have been hampered – no surprise – by difficulty in getting patients to achieve and maintain significant weight loss, the rheumatologist noted.

Obesity is an established risk factor for psoriasis. The possibility that obesity among psoriasis patients is also a risk factor for PsA was raised in a study by investigators with the Utah Psoriasis Initiative, who found that self-reported increased body mass index (BMI) at age 18 years was associated with greater risk of PsA (Arch. Dermatol. 2010;146:721-6).

The Utah finding that greater obesity contributes to an increased risk of PsA has since been confirmed in an impressively large cohort study using data from The Health Improvement Network (THIN), a general practice electronic medical records database that includes more than 7.5 million U.K. patients. THIN is a newer database that is separate from the renowned U.K. General Practice Research Database, which has generated key findings on psoriasis as an independent cardiovascular risk factor.

At last year’s annual meeting of the American College of Rheumatology, THIN investigators reported that among 75,395 THIN enrollees with psoriasis followed for a mean of 5 years, 976 developed PsA.

The incidence of PsA was 23.09 cases/10,000 person-years in subjects whose first BMI measurement after diagnosis of psoriasis showed a BMI of less than 25 kg/m². The incidence climbed stepwise with increasing BMI. Among subjects with a BMI of 25-29.9 kg/m², the incidence was 25.37 cases/10,000 person-years. For those with a BMI of 30-34.9 kg/m², it was 29.33 cases/10,000, while in those with a BMI of 35 kg/m² or more the incidence of PsA was 38.04 cases/10,000.

In a multivariate analysis adjusted for potential confounders, the risk of developing PsA was 12% higher in subjects with a BMI of 25-29.9 than in those with a BMI below 25 kg/m², 46% greater in those with a BMI of 30-34.9 kg/m², and 75% higher in subjects with a BMI of 35 kg/m² or more.

Dr. Ritchlin noted that a separate THIN analysis recently demonstrated that the prevalence of PsA climbs dramatically with more extensive psoriasis independent of other risk factors. This analysis included 4,539 middle-aged psoriasis patients. The overall prevalence of PsA was 8.4%. The lifetime prevalence of PsA was 4.5% among patients whose psoriasis involved 2% or less of their body surface area (BSA), 9.3% among those with 3%-10% BSA involvement, and 22.1% in subjects whose psoriasis affected more than 10% of their BSA.

"I know you’re all going to say, ‘Wait a minute, I have patients who have almost no psoriasis and yet have psoriatic arthritis.’ That’s very true. I have the same experience. But if you look at population-based data, the more severe your psoriasis, the more likely you are to get psoriatic arthritis," the rheumatologist declared.

He reported serving as a consultant to Abbott, Amgen, Centocor, Genentech, Targacept, UCB, and Wyeth and receiving research funding from multiple sources.

Within 18 months of its launch, almost 2,000 people were enrolled in a new, international online registry for rare autoinflammatory diseases designed to facilitate research and treatment, as well as increase awareness of the conditions.

The registry, called Eurofever and launched in November 2009 with the support of the Executive Agency for Health and Consumers of the European Union (EAHC), includes demographic, clinical, and genetic information on people who have developed familial Mediterranean fever, tumor necrosis factor receptor–associated periodic syndrome (TRAPS), mevalonate kinase deficiency, Behçet’s disease, and other conditions, more than 10 in all. Enrollment is ongoing, and new autoinflammatory conditions will be added as they are recognized.

The Eurofever registry is "available for analysis on clinical presentation, disease course, and response to treatment, and to perform large-scale comparative studies between different conditions," according to its founders. It can be accessed in the member area of the Pediatric Rheumatology International Trial Organisation (PRINTO) website. Enrollment information is on the registry’s website.

The goal of the efforts is to counteract "a major limitation to understanding these rare conditions[,] the fragmentation of clinical experience with very few centers in any country caring for more than a handful of cases," according to principal investigator and pediatric rheumatologist Marco Gattorno of the University of Genoa (Italy) and his associates. The investigators solicited enrollment from pediatric and adult centers known to have an interest in rare autoinflammatory diseases (Ann. Rheum. Dis. 2012 Feb. 29 [doi: 10.1136/annrheumdis-2011-200549]).

So far, the registry includes 916 males and 964 females from 67 centers in 31 countries. Three-quarters are under 18 years of age, consistent with the fact that the conditions tend to present in childhood. Three-quarters also reside in Western Europe; 16% in Turkey, Israel, or North Africa; 6% in Eastern Europe, and the rest in Asia, South America, and Australia.

Although North America and many South American and Asian countries "are not yet covered by the registry, the large number of patients recruited in this first period of the project and the wide geographical distribution is very encouraging and suggests that the network can continue to grow," Dr. Gattorno and his colleagues noted.

The efforts are already paying off. An analysis of registry data resulted in identification of three previously unreported mutations for TRAPS, four for mevalonate kinase deficiency, and two for cryopyrin associated periodic syndromes.

The investigators found that physicians are making the diagnosis more quickly. Although the median delay between disease onset and diagnosis was 7.3 years, there is a "trend towards shorter diagnostic delay in patients born" in the current century – 1.4 years for familial Mediterranean fever, for instance – robably "due to the fact that many of these diseases are recently recognized clinical entities and that genetic diagnosis has ...become relatively widely available in the last few years," they noted.

Even so, "the marked bias towards Western Europe," where there are relatively large number of centers with facilities for genetic analysis, may suggest that recognition remains a problem elsewhere, they noted.*

The EAHC is funding the project, along with PRINTO, Novartis, and the Seventh Framework Programme (2007–2013) of the European Community for Research, Technological Development, and Demonstration Activities.

The authors said they had no relevant financial disclosures.

*CORRECTION: 03/12/2012 An earlier version of this story misstated the number of specialty centers with facilities for genetic analysis.

Within 18 months of its launch, almost 2,000 people were enrolled in a new, international online registry for rare autoinflammatory diseases designed to facilitate research and treatment, as well as increase awareness of the conditions.

The registry, called Eurofever and launched in November 2009 with the support of the Executive Agency for Health and Consumers of the European Union (EAHC), includes demographic, clinical, and genetic information on people who have developed familial Mediterranean fever, tumor necrosis factor receptor–associated periodic syndrome (TRAPS), mevalonate kinase deficiency, Behçet’s disease, and other conditions, more than 10 in all. Enrollment is ongoing, and new autoinflammatory conditions will be added as they are recognized.

The Eurofever registry is "available for analysis on clinical presentation, disease course, and response to treatment, and to perform large-scale comparative studies between different conditions," according to its founders. It can be accessed in the member area of the Pediatric Rheumatology International Trial Organisation (PRINTO) website. Enrollment information is on the registry’s website.

The goal of the efforts is to counteract "a major limitation to understanding these rare conditions[,] the fragmentation of clinical experience with very few centers in any country caring for more than a handful of cases," according to principal investigator and pediatric rheumatologist Marco Gattorno of the University of Genoa (Italy) and his associates. The investigators solicited enrollment from pediatric and adult centers known to have an interest in rare autoinflammatory diseases (Ann. Rheum. Dis. 2012 Feb. 29 [doi: 10.1136/annrheumdis-2011-200549]).

So far, the registry includes 916 males and 964 females from 67 centers in 31 countries. Three-quarters are under 18 years of age, consistent with the fact that the conditions tend to present in childhood. Three-quarters also reside in Western Europe; 16% in Turkey, Israel, or North Africa; 6% in Eastern Europe, and the rest in Asia, South America, and Australia.

Although North America and many South American and Asian countries "are not yet covered by the registry, the large number of patients recruited in this first period of the project and the wide geographical distribution is very encouraging and suggests that the network can continue to grow," Dr. Gattorno and his colleagues noted.

The efforts are already paying off. An analysis of registry data resulted in identification of three previously unreported mutations for TRAPS, four for mevalonate kinase deficiency, and two for cryopyrin associated periodic syndromes.

The investigators found that physicians are making the diagnosis more quickly. Although the median delay between disease onset and diagnosis was 7.3 years, there is a "trend towards shorter diagnostic delay in patients born" in the current century – 1.4 years for familial Mediterranean fever, for instance – robably "due to the fact that many of these diseases are recently recognized clinical entities and that genetic diagnosis has ...become relatively widely available in the last few years," they noted.

Even so, "the marked bias towards Western Europe," where there are relatively large number of centers with facilities for genetic analysis, may suggest that recognition remains a problem elsewhere, they noted.*

The EAHC is funding the project, along with PRINTO, Novartis, and the Seventh Framework Programme (2007–2013) of the European Community for Research, Technological Development, and Demonstration Activities.

The authors said they had no relevant financial disclosures.

*CORRECTION: 03/12/2012 An earlier version of this story misstated the number of specialty centers with facilities for genetic analysis.

Within 18 months of its launch, almost 2,000 people were enrolled in a new, international online registry for rare autoinflammatory diseases designed to facilitate research and treatment, as well as increase awareness of the conditions.

The registry, called Eurofever and launched in November 2009 with the support of the Executive Agency for Health and Consumers of the European Union (EAHC), includes demographic, clinical, and genetic information on people who have developed familial Mediterranean fever, tumor necrosis factor receptor–associated periodic syndrome (TRAPS), mevalonate kinase deficiency, Behçet’s disease, and other conditions, more than 10 in all. Enrollment is ongoing, and new autoinflammatory conditions will be added as they are recognized.

The Eurofever registry is "available for analysis on clinical presentation, disease course, and response to treatment, and to perform large-scale comparative studies between different conditions," according to its founders. It can be accessed in the member area of the Pediatric Rheumatology International Trial Organisation (PRINTO) website. Enrollment information is on the registry’s website.

The goal of the efforts is to counteract "a major limitation to understanding these rare conditions[,] the fragmentation of clinical experience with very few centers in any country caring for more than a handful of cases," according to principal investigator and pediatric rheumatologist Marco Gattorno of the University of Genoa (Italy) and his associates. The investigators solicited enrollment from pediatric and adult centers known to have an interest in rare autoinflammatory diseases (Ann. Rheum. Dis. 2012 Feb. 29 [doi: 10.1136/annrheumdis-2011-200549]).

So far, the registry includes 916 males and 964 females from 67 centers in 31 countries. Three-quarters are under 18 years of age, consistent with the fact that the conditions tend to present in childhood. Three-quarters also reside in Western Europe; 16% in Turkey, Israel, or North Africa; 6% in Eastern Europe, and the rest in Asia, South America, and Australia.

Although North America and many South American and Asian countries "are not yet covered by the registry, the large number of patients recruited in this first period of the project and the wide geographical distribution is very encouraging and suggests that the network can continue to grow," Dr. Gattorno and his colleagues noted.

The efforts are already paying off. An analysis of registry data resulted in identification of three previously unreported mutations for TRAPS, four for mevalonate kinase deficiency, and two for cryopyrin associated periodic syndromes.

The investigators found that physicians are making the diagnosis more quickly. Although the median delay between disease onset and diagnosis was 7.3 years, there is a "trend towards shorter diagnostic delay in patients born" in the current century – 1.4 years for familial Mediterranean fever, for instance – robably "due to the fact that many of these diseases are recently recognized clinical entities and that genetic diagnosis has ...become relatively widely available in the last few years," they noted.

Even so, "the marked bias towards Western Europe," where there are relatively large number of centers with facilities for genetic analysis, may suggest that recognition remains a problem elsewhere, they noted.*

The EAHC is funding the project, along with PRINTO, Novartis, and the Seventh Framework Programme (2007–2013) of the European Community for Research, Technological Development, and Demonstration Activities.

The authors said they had no relevant financial disclosures.

*CORRECTION: 03/12/2012 An earlier version of this story misstated the number of specialty centers with facilities for genetic analysis.

Unexplained shoulder pain and abnormal ultrasound findings of those large joints are part of provisional criteria published on polymyalgia rheumatica.

To be diagnosed with polymyalgia rheumatica (PMR) under the criteria proposed jointly by the American College of Rheumatology and the European League Against Rheumatism, patients should be at least 50 years old, have morning stiffness lasting at least 45 minutes, new hip pain, and elevated C-reactive protein and/or erythrocyte sedimentation rate.

ACR and EULAR based their criteria on findings from a prospective, international, multicenter cohort study, are published in the April issue of Arthritis & Rheumatism.

Additional validation in an external data set is required, and the criteria should not be used for diagnostic purposes, but they do have value for identifying the most appropriate patients for enrollment in clinical trials, and thus could pave the way for new therapeutic approaches and novel treatments for the inflammatory disease, Dr. Bhaskar Dasgupta of Southend University Hospital, Westcliff-on-Sea, U.K. and his colleagues reported (Arthritis Rheum. 2012 April;64:943-54).

PMR is a common condition, but its clinical management varies widely, due largely to considerable uncertainty with respect to diagnosis, disease course, and management, according to Dr. Eric L. Matteson, the study’s senior author, who noted in an interview that a lack of classification criteria has hampered development of rational therapeutic approaches because of difficulties in grouping together appropriate patients for enrollment in clinical studies.

"We have no good, established, and in any way validated criteria for classifying patients with having PMR. All previous criteria were based mainly on expert opinion, so what we did here was look at expert opinion about components of the disease that would help us classify a patient as having PMR, then tested to see which of the features in patients who appear to have PMR by expert diagnosis at the outset were most effective in identifying, for classification purposes, patients as having PMR after they were followed for 6 months," said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

The criteria were based on the findings of a criteria development work group convened in 2005 in response to an ACR/EULAR initiative. The group performed a systematic literature review, and through a multiphase process, identified candidate classification criteria, which were ultimately investigated in the 6-month prospective cohort study of 125 patients with new-onset PMR and 169 comparison patients with conditions mimicking PMR.

A scoring algorithm was developed based on four criteria: morning stiffness for greater than 45 minutes (2 points); hip pain/limited range of motion (1 point), absence of rheumatoid factor (RF) and/or anticitrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point).

"A score of 4 or higher had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. The C statistic for the scoring algorithm was 81%," the investigators said.

The absence of peripheral synovitis or positive RF serology increased the likelihood of PMR.

Additionally, ultrasound was found to significantly improve the specificity of the clinical criteria, improving the C statistic to 82% when added to the scoring algorithm.

"Patients with PMR were more likely to have abnormal ultrasound findings in the shoulder (particularly subdeltoid bursitis and biceps tenosynovitis), and somewhat more likely to have abnormal findings in the hips than [do] comparison subjects as a group," the investigators said, adding that PMR could not be distinguished from RA on the basis of ultrasound, but could be distinguished from non-RA shoulder conditions and subjects without shoulder conditions.

Adding ultrasound to the scoring algorithm improved the C statistic of 82%.

The ultrasound finding mark the first time this technology has been systematically utilized in a longitudinal study for this purpose, Dr. Matteson said, adding that there are, indeed, typical findings on ultrasound in PMR, and although ultrasound alone can’t be used to identify PMR as opposed to RA, the findings can be helpful for classification of patients with PMR.

He also noted that the ultrasound features seen in PMR at the outset improved with treatment.

Patients and controls in the study were recruited from 21 community-based and academic rheumatology clinics in 10 European countries and the United States. All were aged 50 years or older, had new-onset bilateral shoulder pain, and no corticosteroid treatment within 12 weeks before the study. Patients had received a diagnosis of PMR, and corticosteroid treatment was initiated after enrollment.

The non-PMR comparison cohort included subjects with a variety of conditions that need to be distinguished from PMR, in both primary and secondary care, the investigators said.

Initial diagnoses in this group of patients included new-onset RA, connective tissue disease, various shoulder conditions, fibromyalgia, and generalized osteoarthritis, among others, they noted.

"Newer concepts of PMR are revealed by this and other recent studies – heterogeneity at presentation and course, lack of uniform responsiveness to low-dose steroids, and overlap with inflammatory arthritis. However, we feel that at present these classification criteria provide a basic framework for developing clinical trials of novel therapies in PMR," the investigators said, adding that C statistic of 81%, for the algorithm (82% when ultrasound is included), "exceeds the threshold of 80% that is conventionally considered to be useful in clinical decision-making."

"In our view, this approach can now be used to test eligibility for trials with newer therapies in PMR," they said.

The next steps are to validate the classification criteria in another group of patients and to identify better biomarkers for diagnosis and assessment of disease activity and disease damage, Dr. Matteson noted.

The provisional classification criteria are also published simultaneously in the April issue of Annals of the Rheumatic Diseases.

This work was supported by the ACR, EULAR, and the Mayo Foundation, as well as by Biobanque de Picardie in Amiens, France, and by the Ministero de Ciencia y Tecnologia, Spain. Numerous study authors reported various disclosures. Details are included in the full text of the article.

Unexplained shoulder pain and abnormal ultrasound findings of those large joints are part of provisional criteria published on polymyalgia rheumatica.

To be diagnosed with polymyalgia rheumatica (PMR) under the criteria proposed jointly by the American College of Rheumatology and the European League Against Rheumatism, patients should be at least 50 years old, have morning stiffness lasting at least 45 minutes, new hip pain, and elevated C-reactive protein and/or erythrocyte sedimentation rate.

ACR and EULAR based their criteria on findings from a prospective, international, multicenter cohort study, are published in the April issue of Arthritis & Rheumatism.

Additional validation in an external data set is required, and the criteria should not be used for diagnostic purposes, but they do have value for identifying the most appropriate patients for enrollment in clinical trials, and thus could pave the way for new therapeutic approaches and novel treatments for the inflammatory disease, Dr. Bhaskar Dasgupta of Southend University Hospital, Westcliff-on-Sea, U.K. and his colleagues reported (Arthritis Rheum. 2012 April;64:943-54).

PMR is a common condition, but its clinical management varies widely, due largely to considerable uncertainty with respect to diagnosis, disease course, and management, according to Dr. Eric L. Matteson, the study’s senior author, who noted in an interview that a lack of classification criteria has hampered development of rational therapeutic approaches because of difficulties in grouping together appropriate patients for enrollment in clinical studies.

"We have no good, established, and in any way validated criteria for classifying patients with having PMR. All previous criteria were based mainly on expert opinion, so what we did here was look at expert opinion about components of the disease that would help us classify a patient as having PMR, then tested to see which of the features in patients who appear to have PMR by expert diagnosis at the outset were most effective in identifying, for classification purposes, patients as having PMR after they were followed for 6 months," said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

The criteria were based on the findings of a criteria development work group convened in 2005 in response to an ACR/EULAR initiative. The group performed a systematic literature review, and through a multiphase process, identified candidate classification criteria, which were ultimately investigated in the 6-month prospective cohort study of 125 patients with new-onset PMR and 169 comparison patients with conditions mimicking PMR.

A scoring algorithm was developed based on four criteria: morning stiffness for greater than 45 minutes (2 points); hip pain/limited range of motion (1 point), absence of rheumatoid factor (RF) and/or anticitrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point).

"A score of 4 or higher had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. The C statistic for the scoring algorithm was 81%," the investigators said.

The absence of peripheral synovitis or positive RF serology increased the likelihood of PMR.

Additionally, ultrasound was found to significantly improve the specificity of the clinical criteria, improving the C statistic to 82% when added to the scoring algorithm.

"Patients with PMR were more likely to have abnormal ultrasound findings in the shoulder (particularly subdeltoid bursitis and biceps tenosynovitis), and somewhat more likely to have abnormal findings in the hips than [do] comparison subjects as a group," the investigators said, adding that PMR could not be distinguished from RA on the basis of ultrasound, but could be distinguished from non-RA shoulder conditions and subjects without shoulder conditions.

Adding ultrasound to the scoring algorithm improved the C statistic of 82%.

The ultrasound finding mark the first time this technology has been systematically utilized in a longitudinal study for this purpose, Dr. Matteson said, adding that there are, indeed, typical findings on ultrasound in PMR, and although ultrasound alone can’t be used to identify PMR as opposed to RA, the findings can be helpful for classification of patients with PMR.

He also noted that the ultrasound features seen in PMR at the outset improved with treatment.

Patients and controls in the study were recruited from 21 community-based and academic rheumatology clinics in 10 European countries and the United States. All were aged 50 years or older, had new-onset bilateral shoulder pain, and no corticosteroid treatment within 12 weeks before the study. Patients had received a diagnosis of PMR, and corticosteroid treatment was initiated after enrollment.

The non-PMR comparison cohort included subjects with a variety of conditions that need to be distinguished from PMR, in both primary and secondary care, the investigators said.

Initial diagnoses in this group of patients included new-onset RA, connective tissue disease, various shoulder conditions, fibromyalgia, and generalized osteoarthritis, among others, they noted.

"Newer concepts of PMR are revealed by this and other recent studies – heterogeneity at presentation and course, lack of uniform responsiveness to low-dose steroids, and overlap with inflammatory arthritis. However, we feel that at present these classification criteria provide a basic framework for developing clinical trials of novel therapies in PMR," the investigators said, adding that C statistic of 81%, for the algorithm (82% when ultrasound is included), "exceeds the threshold of 80% that is conventionally considered to be useful in clinical decision-making."

"In our view, this approach can now be used to test eligibility for trials with newer therapies in PMR," they said.

The next steps are to validate the classification criteria in another group of patients and to identify better biomarkers for diagnosis and assessment of disease activity and disease damage, Dr. Matteson noted.

The provisional classification criteria are also published simultaneously in the April issue of Annals of the Rheumatic Diseases.

This work was supported by the ACR, EULAR, and the Mayo Foundation, as well as by Biobanque de Picardie in Amiens, France, and by the Ministero de Ciencia y Tecnologia, Spain. Numerous study authors reported various disclosures. Details are included in the full text of the article.

Unexplained shoulder pain and abnormal ultrasound findings of those large joints are part of provisional criteria published on polymyalgia rheumatica.

To be diagnosed with polymyalgia rheumatica (PMR) under the criteria proposed jointly by the American College of Rheumatology and the European League Against Rheumatism, patients should be at least 50 years old, have morning stiffness lasting at least 45 minutes, new hip pain, and elevated C-reactive protein and/or erythrocyte sedimentation rate.

ACR and EULAR based their criteria on findings from a prospective, international, multicenter cohort study, are published in the April issue of Arthritis & Rheumatism.

Additional validation in an external data set is required, and the criteria should not be used for diagnostic purposes, but they do have value for identifying the most appropriate patients for enrollment in clinical trials, and thus could pave the way for new therapeutic approaches and novel treatments for the inflammatory disease, Dr. Bhaskar Dasgupta of Southend University Hospital, Westcliff-on-Sea, U.K. and his colleagues reported (Arthritis Rheum. 2012 April;64:943-54).

PMR is a common condition, but its clinical management varies widely, due largely to considerable uncertainty with respect to diagnosis, disease course, and management, according to Dr. Eric L. Matteson, the study’s senior author, who noted in an interview that a lack of classification criteria has hampered development of rational therapeutic approaches because of difficulties in grouping together appropriate patients for enrollment in clinical studies.

"We have no good, established, and in any way validated criteria for classifying patients with having PMR. All previous criteria were based mainly on expert opinion, so what we did here was look at expert opinion about components of the disease that would help us classify a patient as having PMR, then tested to see which of the features in patients who appear to have PMR by expert diagnosis at the outset were most effective in identifying, for classification purposes, patients as having PMR after they were followed for 6 months," said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

The criteria were based on the findings of a criteria development work group convened in 2005 in response to an ACR/EULAR initiative. The group performed a systematic literature review, and through a multiphase process, identified candidate classification criteria, which were ultimately investigated in the 6-month prospective cohort study of 125 patients with new-onset PMR and 169 comparison patients with conditions mimicking PMR.

A scoring algorithm was developed based on four criteria: morning stiffness for greater than 45 minutes (2 points); hip pain/limited range of motion (1 point), absence of rheumatoid factor (RF) and/or anticitrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point).

"A score of 4 or higher had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. The C statistic for the scoring algorithm was 81%," the investigators said.

The absence of peripheral synovitis or positive RF serology increased the likelihood of PMR.

Additionally, ultrasound was found to significantly improve the specificity of the clinical criteria, improving the C statistic to 82% when added to the scoring algorithm.

"Patients with PMR were more likely to have abnormal ultrasound findings in the shoulder (particularly subdeltoid bursitis and biceps tenosynovitis), and somewhat more likely to have abnormal findings in the hips than [do] comparison subjects as a group," the investigators said, adding that PMR could not be distinguished from RA on the basis of ultrasound, but could be distinguished from non-RA shoulder conditions and subjects without shoulder conditions.

Adding ultrasound to the scoring algorithm improved the C statistic of 82%.

The ultrasound finding mark the first time this technology has been systematically utilized in a longitudinal study for this purpose, Dr. Matteson said, adding that there are, indeed, typical findings on ultrasound in PMR, and although ultrasound alone can’t be used to identify PMR as opposed to RA, the findings can be helpful for classification of patients with PMR.

He also noted that the ultrasound features seen in PMR at the outset improved with treatment.

Patients and controls in the study were recruited from 21 community-based and academic rheumatology clinics in 10 European countries and the United States. All were aged 50 years or older, had new-onset bilateral shoulder pain, and no corticosteroid treatment within 12 weeks before the study. Patients had received a diagnosis of PMR, and corticosteroid treatment was initiated after enrollment.

The non-PMR comparison cohort included subjects with a variety of conditions that need to be distinguished from PMR, in both primary and secondary care, the investigators said.

Initial diagnoses in this group of patients included new-onset RA, connective tissue disease, various shoulder conditions, fibromyalgia, and generalized osteoarthritis, among others, they noted.

"Newer concepts of PMR are revealed by this and other recent studies – heterogeneity at presentation and course, lack of uniform responsiveness to low-dose steroids, and overlap with inflammatory arthritis. However, we feel that at present these classification criteria provide a basic framework for developing clinical trials of novel therapies in PMR," the investigators said, adding that C statistic of 81%, for the algorithm (82% when ultrasound is included), "exceeds the threshold of 80% that is conventionally considered to be useful in clinical decision-making."

"In our view, this approach can now be used to test eligibility for trials with newer therapies in PMR," they said.

The next steps are to validate the classification criteria in another group of patients and to identify better biomarkers for diagnosis and assessment of disease activity and disease damage, Dr. Matteson noted.

The provisional classification criteria are also published simultaneously in the April issue of Annals of the Rheumatic Diseases.

This work was supported by the ACR, EULAR, and the Mayo Foundation, as well as by Biobanque de Picardie in Amiens, France, and by the Ministero de Ciencia y Tecnologia, Spain. Numerous study authors reported various disclosures. Details are included in the full text of the article.