Sharon Worcester

LAS VEGAS – Dermatologists, like all physicians, play an important role not just in the treatment of disease, but also in the prevention of disease, and that means vaccinating patients when indicated, according to Dr. Stephen K. Tyring.

The varicella vaccines, including the chicken pox and shingles vaccines, and the human papillomavirus (HPV), hepatitis, and influenza virus vaccines are among those to consider offering to patients when appropriate, Dr. Tyring said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Concerns arise, however, when it comes to vaccinating psoriasis patients who are – or will be – treated with biologics.

Ideally, vaccination should be offered before treatment is initiated, he said, but for some patients – such as those who are under the age for which their insurance company will cover a vaccine (age 50 or 60 for the shingles vaccine, depending on the insurance company, for example) – this may not be possible. In those already taking a biologic drug, the question is how to vaccinate safely and without interfering with treatment efficacy, he said.

"What we usually do – and there’s no absolute golden rule – is ask the patient to stop the drug for one to two half-lives of the drug," said Dr. Tyring of the University of Texas, Houston. We suggest stopping one half-life for killed, subunit, or recombinant virus vaccines and stopping for two half-lives for live attenuated virus vaccines.

With the tumor necrosis factor (TNF) inhibitor etanercept (Enbrel), for example, that means skipping one to two weekly injections.

"That’s a little bit more than a half-life, but if a patient is using Enbrel once or twice a week, the next week, instead of injecting the Enbrel, they can just come in and get the shingles vaccine [Zostavax]," he said.

Adalimumab (Humira), another anti-TNF drug, has a longer half-life, so that has to be taken into account. Things get a little more complicated when it comes to patients treated with ustekinumab (Stelera), which has a particularly long half-life, he noted.

"It’s not quite as easy, because it’s not clear how long to wait after Stelera to give a vaccine. Most efficacy is seen in the first month, and when patients come back at 3 months, they often are starting to get a little psoriasis back. Therefore, 2 months following an injection of Stelera is about the right time to get the vaccine; that way you get the minimum immunosuppression and the maximum chance to respond," he said.

Similarly, with other vaccines like the Gardasil HPV vaccine and the hepatitis A and B vaccines that require a series of shots, the biologic should be stopped for a half-life. This will mean skipping biologic dosing multiple times, but in most cases this won’t be problematic, because it typically takes about 3 months for a patient who is clear to experience significant psoriasis recurrence.

"There’s really no danger in skipping," he said.

While some may advocate waiting two half-lives after vaccination, most experts agree that is unnecessary for killed, recombinant, or subunit (for example, injectable influenza) virus vaccines but is advisable for live attenuated virus vaccines like the intranasal influenza virus vaccine or the herpes zoster vaccine Zostavax, he said.

Dr. Tyring also noted during his presentation that in his experience, concerns about increased infection risk in patients taking TNF inhibitors have been unfounded. In fact, treatment appears to provide an unexpected benefit for those who do become infected with herpes zoster: a reduced risk of postherpetic neuralgia, even among older individuals who are generally at particularly high risk.

After noticing this benefit in his own patients, Dr. Tyring asked his colleagues and found that they, too, had noticed a similar pattern. In 2011, he and his colleagues published a retrospective study of 206 patients on TNF inhibitors who developed herpes zoster, and with only two exceptions involving patients on both a TNF inhibitor and methotrexate, patients universally experienced milder symptoms if they developed shingles while on a TNF inhibitor, he said, noting that this is much lower than rates reported in the literature in the general population (J. Med. Virol. 2011;83:2051-5).

SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – Dermatologists, like all physicians, play an important role not just in the treatment of disease, but also in the prevention of disease, and that means vaccinating patients when indicated, according to Dr. Stephen K. Tyring.

The varicella vaccines, including the chicken pox and shingles vaccines, and the human papillomavirus (HPV), hepatitis, and influenza virus vaccines are among those to consider offering to patients when appropriate, Dr. Tyring said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Concerns arise, however, when it comes to vaccinating psoriasis patients who are – or will be – treated with biologics.

Ideally, vaccination should be offered before treatment is initiated, he said, but for some patients – such as those who are under the age for which their insurance company will cover a vaccine (age 50 or 60 for the shingles vaccine, depending on the insurance company, for example) – this may not be possible. In those already taking a biologic drug, the question is how to vaccinate safely and without interfering with treatment efficacy, he said.

"What we usually do – and there’s no absolute golden rule – is ask the patient to stop the drug for one to two half-lives of the drug," said Dr. Tyring of the University of Texas, Houston. We suggest stopping one half-life for killed, subunit, or recombinant virus vaccines and stopping for two half-lives for live attenuated virus vaccines.

With the tumor necrosis factor (TNF) inhibitor etanercept (Enbrel), for example, that means skipping one to two weekly injections.

"That’s a little bit more than a half-life, but if a patient is using Enbrel once or twice a week, the next week, instead of injecting the Enbrel, they can just come in and get the shingles vaccine [Zostavax]," he said.

Adalimumab (Humira), another anti-TNF drug, has a longer half-life, so that has to be taken into account. Things get a little more complicated when it comes to patients treated with ustekinumab (Stelera), which has a particularly long half-life, he noted.

"It’s not quite as easy, because it’s not clear how long to wait after Stelera to give a vaccine. Most efficacy is seen in the first month, and when patients come back at 3 months, they often are starting to get a little psoriasis back. Therefore, 2 months following an injection of Stelera is about the right time to get the vaccine; that way you get the minimum immunosuppression and the maximum chance to respond," he said.

Similarly, with other vaccines like the Gardasil HPV vaccine and the hepatitis A and B vaccines that require a series of shots, the biologic should be stopped for a half-life. This will mean skipping biologic dosing multiple times, but in most cases this won’t be problematic, because it typically takes about 3 months for a patient who is clear to experience significant psoriasis recurrence.

"There’s really no danger in skipping," he said.

While some may advocate waiting two half-lives after vaccination, most experts agree that is unnecessary for killed, recombinant, or subunit (for example, injectable influenza) virus vaccines but is advisable for live attenuated virus vaccines like the intranasal influenza virus vaccine or the herpes zoster vaccine Zostavax, he said.

Dr. Tyring also noted during his presentation that in his experience, concerns about increased infection risk in patients taking TNF inhibitors have been unfounded. In fact, treatment appears to provide an unexpected benefit for those who do become infected with herpes zoster: a reduced risk of postherpetic neuralgia, even among older individuals who are generally at particularly high risk.

After noticing this benefit in his own patients, Dr. Tyring asked his colleagues and found that they, too, had noticed a similar pattern. In 2011, he and his colleagues published a retrospective study of 206 patients on TNF inhibitors who developed herpes zoster, and with only two exceptions involving patients on both a TNF inhibitor and methotrexate, patients universally experienced milder symptoms if they developed shingles while on a TNF inhibitor, he said, noting that this is much lower than rates reported in the literature in the general population (J. Med. Virol. 2011;83:2051-5).

SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – Dermatologists, like all physicians, play an important role not just in the treatment of disease, but also in the prevention of disease, and that means vaccinating patients when indicated, according to Dr. Stephen K. Tyring.

The varicella vaccines, including the chicken pox and shingles vaccines, and the human papillomavirus (HPV), hepatitis, and influenza virus vaccines are among those to consider offering to patients when appropriate, Dr. Tyring said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Concerns arise, however, when it comes to vaccinating psoriasis patients who are – or will be – treated with biologics.

Ideally, vaccination should be offered before treatment is initiated, he said, but for some patients – such as those who are under the age for which their insurance company will cover a vaccine (age 50 or 60 for the shingles vaccine, depending on the insurance company, for example) – this may not be possible. In those already taking a biologic drug, the question is how to vaccinate safely and without interfering with treatment efficacy, he said.

"What we usually do – and there’s no absolute golden rule – is ask the patient to stop the drug for one to two half-lives of the drug," said Dr. Tyring of the University of Texas, Houston. We suggest stopping one half-life for killed, subunit, or recombinant virus vaccines and stopping for two half-lives for live attenuated virus vaccines.

With the tumor necrosis factor (TNF) inhibitor etanercept (Enbrel), for example, that means skipping one to two weekly injections.

"That’s a little bit more than a half-life, but if a patient is using Enbrel once or twice a week, the next week, instead of injecting the Enbrel, they can just come in and get the shingles vaccine [Zostavax]," he said.

Adalimumab (Humira), another anti-TNF drug, has a longer half-life, so that has to be taken into account. Things get a little more complicated when it comes to patients treated with ustekinumab (Stelera), which has a particularly long half-life, he noted.

"It’s not quite as easy, because it’s not clear how long to wait after Stelera to give a vaccine. Most efficacy is seen in the first month, and when patients come back at 3 months, they often are starting to get a little psoriasis back. Therefore, 2 months following an injection of Stelera is about the right time to get the vaccine; that way you get the minimum immunosuppression and the maximum chance to respond," he said.

Similarly, with other vaccines like the Gardasil HPV vaccine and the hepatitis A and B vaccines that require a series of shots, the biologic should be stopped for a half-life. This will mean skipping biologic dosing multiple times, but in most cases this won’t be problematic, because it typically takes about 3 months for a patient who is clear to experience significant psoriasis recurrence.

"There’s really no danger in skipping," he said.

While some may advocate waiting two half-lives after vaccination, most experts agree that is unnecessary for killed, recombinant, or subunit (for example, injectable influenza) virus vaccines but is advisable for live attenuated virus vaccines like the intranasal influenza virus vaccine or the herpes zoster vaccine Zostavax, he said.

Dr. Tyring also noted during his presentation that in his experience, concerns about increased infection risk in patients taking TNF inhibitors have been unfounded. In fact, treatment appears to provide an unexpected benefit for those who do become infected with herpes zoster: a reduced risk of postherpetic neuralgia, even among older individuals who are generally at particularly high risk.

After noticing this benefit in his own patients, Dr. Tyring asked his colleagues and found that they, too, had noticed a similar pattern. In 2011, he and his colleagues published a retrospective study of 206 patients on TNF inhibitors who developed herpes zoster, and with only two exceptions involving patients on both a TNF inhibitor and methotrexate, patients universally experienced milder symptoms if they developed shingles while on a TNF inhibitor, he said, noting that this is much lower than rates reported in the literature in the general population (J. Med. Virol. 2011;83:2051-5).

SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – Dermatologists, like all physicians, play an important role not just in the treatment of disease, but also in the prevention of disease, and that means vaccinating patients when indicated, according to Dr. Stephen K. Tyring.

The varicella vaccines, including the chicken pox and shingles vaccines, and the human papillomavirus (HPV), hepatitis, and influenza virus vaccines are among those to consider offering to patients when appropriate, Dr. Tyring said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Concerns arise, however, when it comes to vaccinating psoriasis patients who are – or will be – treated with biologics.

Ideally, vaccination should be offered before treatment is initiated, he said, but for some patients – such as those who are under the age for which their insurance company will cover a vaccine (age 50 or 60 for the shingles vaccine, depending on the insurance company, for example) – this may not be possible. In those already taking a biologic drug, the question is how to vaccinate safely and without interfering with treatment efficacy, he said.

"What we usually do – and there’s no absolute golden rule – is ask the patient to stop the drug for one to two half-lives of the drug," said Dr. Tyring of the University of Texas, Houston. We suggest stopping one half-life for killed, subunit, or recombinant virus vaccines and stopping for two half-lives for live attenuated virus vaccines.

With the tumor necrosis factor (TNF) inhibitor etanercept (Enbrel), for example, that means skipping one to two weekly injections.

"That’s a little bit more than a half-life, but if a patient is using Enbrel once or twice a week, the next week, instead of injecting the Enbrel, they can just come in and get the shingles vaccine [Zostavax]," he said.

Adalimumab (Humira), another anti-TNF drug, has a longer half-life, so that has to be taken into account. Things get a little more complicated when it comes to patients treated with ustekinumab (Stelera), which has a particularly long half-life, he noted.

"It’s not quite as easy, because it’s not clear how long to wait after Stelera to give a vaccine. Most efficacy is seen in the first month, and when patients come back at 3 months, they often are starting to get a little psoriasis back. Therefore, 2 months following an injection of Stelera is about the right time to get the vaccine; that way you get the minimum immunosuppression and the maximum chance to respond," he said.

Similarly, with other vaccines like the Gardasil HPV vaccine and the hepatitis A and B vaccines that require a series of shots, the biologic should be stopped for a half-life. This will mean skipping biologic dosing multiple times, but in most cases this won’t be problematic, because it typically takes about 3 months for a patient who is clear to experience significant psoriasis recurrence.

"There’s really no danger in skipping," he said.

While some may advocate waiting two half-lives after vaccination, most experts agree that is unnecessary for killed, recombinant, or subunit (for example, injectable influenza) virus vaccines but is advisable for live attenuated virus vaccines like the intranasal influenza virus vaccine or the herpes zoster vaccine Zostavax, he said.

Dr. Tyring also noted during his presentation that in his experience, concerns about increased infection risk in patients taking TNF inhibitors have been unfounded. In fact, treatment appears to provide an unexpected benefit for those who do become infected with herpes zoster: a reduced risk of postherpetic neuralgia, even among older individuals who are generally at particularly high risk.

After noticing this benefit in his own patients, Dr. Tyring asked his colleagues and found that they, too, had noticed a similar pattern. In 2011, he and his colleagues published a retrospective study of 206 patients on TNF inhibitors who developed herpes zoster, and with only two exceptions involving patients on both a TNF inhibitor and methotrexate, patients universally experienced milder symptoms if they developed shingles while on a TNF inhibitor, he said, noting that this is much lower than rates reported in the literature in the general population (J. Med. Virol. 2011;83:2051-5).

SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – Dermatologists, like all physicians, play an important role not just in the treatment of disease, but also in the prevention of disease, and that means vaccinating patients when indicated, according to Dr. Stephen K. Tyring.

The varicella vaccines, including the chicken pox and shingles vaccines, and the human papillomavirus (HPV), hepatitis, and influenza virus vaccines are among those to consider offering to patients when appropriate, Dr. Tyring said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Concerns arise, however, when it comes to vaccinating psoriasis patients who are – or will be – treated with biologics.

Ideally, vaccination should be offered before treatment is initiated, he said, but for some patients – such as those who are under the age for which their insurance company will cover a vaccine (age 50 or 60 for the shingles vaccine, depending on the insurance company, for example) – this may not be possible. In those already taking a biologic drug, the question is how to vaccinate safely and without interfering with treatment efficacy, he said.

"What we usually do – and there’s no absolute golden rule – is ask the patient to stop the drug for one to two half-lives of the drug," said Dr. Tyring of the University of Texas, Houston. We suggest stopping one half-life for killed, subunit, or recombinant virus vaccines and stopping for two half-lives for live attenuated virus vaccines.

With the tumor necrosis factor (TNF) inhibitor etanercept (Enbrel), for example, that means skipping one to two weekly injections.

"That’s a little bit more than a half-life, but if a patient is using Enbrel once or twice a week, the next week, instead of injecting the Enbrel, they can just come in and get the shingles vaccine [Zostavax]," he said.

Adalimumab (Humira), another anti-TNF drug, has a longer half-life, so that has to be taken into account. Things get a little more complicated when it comes to patients treated with ustekinumab (Stelera), which has a particularly long half-life, he noted.

"It’s not quite as easy, because it’s not clear how long to wait after Stelera to give a vaccine. Most efficacy is seen in the first month, and when patients come back at 3 months, they often are starting to get a little psoriasis back. Therefore, 2 months following an injection of Stelera is about the right time to get the vaccine; that way you get the minimum immunosuppression and the maximum chance to respond," he said.

Similarly, with other vaccines like the Gardasil HPV vaccine and the hepatitis A and B vaccines that require a series of shots, the biologic should be stopped for a half-life. This will mean skipping biologic dosing multiple times, but in most cases this won’t be problematic, because it typically takes about 3 months for a patient who is clear to experience significant psoriasis recurrence.

"There’s really no danger in skipping," he said.

While some may advocate waiting two half-lives after vaccination, most experts agree that is unnecessary for killed, recombinant, or subunit (for example, injectable influenza) virus vaccines but is advisable for live attenuated virus vaccines like the intranasal influenza virus vaccine or the herpes zoster vaccine Zostavax, he said.

Dr. Tyring also noted during his presentation that in his experience, concerns about increased infection risk in patients taking TNF inhibitors have been unfounded. In fact, treatment appears to provide an unexpected benefit for those who do become infected with herpes zoster: a reduced risk of postherpetic neuralgia, even among older individuals who are generally at particularly high risk.

After noticing this benefit in his own patients, Dr. Tyring asked his colleagues and found that they, too, had noticed a similar pattern. In 2011, he and his colleagues published a retrospective study of 206 patients on TNF inhibitors who developed herpes zoster, and with only two exceptions involving patients on both a TNF inhibitor and methotrexate, patients universally experienced milder symptoms if they developed shingles while on a TNF inhibitor, he said, noting that this is much lower than rates reported in the literature in the general population (J. Med. Virol. 2011;83:2051-5).

SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – Dermatologists, like all physicians, play an important role not just in the treatment of disease, but also in the prevention of disease, and that means vaccinating patients when indicated, according to Dr. Stephen K. Tyring.

The varicella vaccines, including the chicken pox and shingles vaccines, and the human papillomavirus (HPV), hepatitis, and influenza virus vaccines are among those to consider offering to patients when appropriate, Dr. Tyring said at the Skin Disease Education Foundation’s annual Las Vegas dermatology seminar.

Concerns arise, however, when it comes to vaccinating psoriasis patients who are – or will be – treated with biologics.

Ideally, vaccination should be offered before treatment is initiated, he said, but for some patients – such as those who are under the age for which their insurance company will cover a vaccine (age 50 or 60 for the shingles vaccine, depending on the insurance company, for example) – this may not be possible. In those already taking a biologic drug, the question is how to vaccinate safely and without interfering with treatment efficacy, he said.

"What we usually do – and there’s no absolute golden rule – is ask the patient to stop the drug for one to two half-lives of the drug," said Dr. Tyring of the University of Texas, Houston. We suggest stopping one half-life for killed, subunit, or recombinant virus vaccines and stopping for two half-lives for live attenuated virus vaccines.

With the tumor necrosis factor (TNF) inhibitor etanercept (Enbrel), for example, that means skipping one to two weekly injections.

"That’s a little bit more than a half-life, but if a patient is using Enbrel once or twice a week, the next week, instead of injecting the Enbrel, they can just come in and get the shingles vaccine [Zostavax]," he said.

Adalimumab (Humira), another anti-TNF drug, has a longer half-life, so that has to be taken into account. Things get a little more complicated when it comes to patients treated with ustekinumab (Stelera), which has a particularly long half-life, he noted.

"It’s not quite as easy, because it’s not clear how long to wait after Stelera to give a vaccine. Most efficacy is seen in the first month, and when patients come back at 3 months, they often are starting to get a little psoriasis back. Therefore, 2 months following an injection of Stelera is about the right time to get the vaccine; that way you get the minimum immunosuppression and the maximum chance to respond," he said.

Similarly, with other vaccines like the Gardasil HPV vaccine and the hepatitis A and B vaccines that require a series of shots, the biologic should be stopped for a half-life. This will mean skipping biologic dosing multiple times, but in most cases this won’t be problematic, because it typically takes about 3 months for a patient who is clear to experience significant psoriasis recurrence.

"There’s really no danger in skipping," he said.

While some may advocate waiting two half-lives after vaccination, most experts agree that is unnecessary for killed, recombinant, or subunit (for example, injectable influenza) virus vaccines but is advisable for live attenuated virus vaccines like the intranasal influenza virus vaccine or the herpes zoster vaccine Zostavax, he said.

Dr. Tyring also noted during his presentation that in his experience, concerns about increased infection risk in patients taking TNF inhibitors have been unfounded. In fact, treatment appears to provide an unexpected benefit for those who do become infected with herpes zoster: a reduced risk of postherpetic neuralgia, even among older individuals who are generally at particularly high risk.

After noticing this benefit in his own patients, Dr. Tyring asked his colleagues and found that they, too, had noticed a similar pattern. In 2011, he and his colleagues published a retrospective study of 206 patients on TNF inhibitors who developed herpes zoster, and with only two exceptions involving patients on both a TNF inhibitor and methotrexate, patients universally experienced milder symptoms if they developed shingles while on a TNF inhibitor, he said, noting that this is much lower than rates reported in the literature in the general population (J. Med. Virol. 2011;83:2051-5).

SDEF and this news organization are owned by Frontline Medical Communications.

ORLANDO – The proportion of pediatric musculoskeletal infections involving methicillin-resistant Staphylococcus aureus vs. methicillin-sensitive S. aureus has increased dramatically over the past decade, according to a retrospective review of cases.

Between 2001 and 2010, 148 patients at the Children’s Hospital of Philadelphia presented with acute musculoskeletal S. aureus infection, and overall, 37 of those involved methicillin-resistant S. aureus (MRSA), Eric Sarkissian reported at the annual meeting of the American Academy of Pediatrics conference.

The proportion of musculoskeletal cases involving MRSA increased from 12% in 2001-2002 to about 35% in 2010, said Mr. Sarkissian, a 4th-year medical student at Drexel University, Philadelphia.

"Furthermore, we found that MRSA infections were associated with a significantly more complicated hospital stay," Mr. Sarkissian said.

Courtesy Janice Haney Carr/CDC

MRSA and methicillin-sensitive S. aureus (MSSA) patients were undergoing magnetic resonance imaging at similar rates, but the average duration of hospitalization was longer for the MRSA patients (13 vs. 8 days), and more MRSA patients required multiple surgical procedures (38% vs. 15%), he said.

In addition, mean presenting C-reactive protein levels were higher in the MRSA vs. MSSA patients (14.7 mg/L vs. 9.8 mg/L), as were infection-related complications, including deep vein thrombosis, septic emboli, septic shock, recurrent infection, and/or avascular necrosis (22% vs. 6%).

MRSA patients also were more often admitted to the ICU for further treatment.

Patients included in this series – the largest known case series of children and adolescents presenting with culture-positive S. aureus osteomyelitis and/or septic arthritis – were consecutive patients with positive cultures of blood, bone, or joint aspirate. Those with postoperative and chronic infections were excluded in an effort to minimize bias caused by nosocomial infections, Mr. Sarkissian noted.

The findings support the ongoing concern that MRSA is evolving and becoming more virulent and invasive over time, compared with MSSA infections. In addition, the findings underscore the need for prompt recognition and aggressive treatment of MRSA musculoskeletal infections, as early recognition is paramount for avoiding sequelae and improving patient outcomes.

"A high index of suspicion is still necessary in the setting of musculoskeletal infections in pediatric patients. Multidisciplinary care provides the most successful opportunity for having improved patient outcomes, and this requires employing broad spectrum antibiotic coverage, using aggressive surgical management, and having an awareness of potential complications," Mr. Sarkissian said.

While clinical prediction models have been developed to help in detecting MRSA infections, outcomes using the models have varied geographically, suggesting that there are unknown regional differences among MRSA cases. It remains to be seen whether available models will be useful for identifying MRSA at presentation, he said.

Mr. Sarkissian reported having no disclosures.

ORLANDO – The proportion of pediatric musculoskeletal infections involving methicillin-resistant Staphylococcus aureus vs. methicillin-sensitive S. aureus has increased dramatically over the past decade, according to a retrospective review of cases.

Between 2001 and 2010, 148 patients at the Children’s Hospital of Philadelphia presented with acute musculoskeletal S. aureus infection, and overall, 37 of those involved methicillin-resistant S. aureus (MRSA), Eric Sarkissian reported at the annual meeting of the American Academy of Pediatrics conference.

The proportion of musculoskeletal cases involving MRSA increased from 12% in 2001-2002 to about 35% in 2010, said Mr. Sarkissian, a 4th-year medical student at Drexel University, Philadelphia.

"Furthermore, we found that MRSA infections were associated with a significantly more complicated hospital stay," Mr. Sarkissian said.

Courtesy Janice Haney Carr/CDC

MRSA and methicillin-sensitive S. aureus (MSSA) patients were undergoing magnetic resonance imaging at similar rates, but the average duration of hospitalization was longer for the MRSA patients (13 vs. 8 days), and more MRSA patients required multiple surgical procedures (38% vs. 15%), he said.

In addition, mean presenting C-reactive protein levels were higher in the MRSA vs. MSSA patients (14.7 mg/L vs. 9.8 mg/L), as were infection-related complications, including deep vein thrombosis, septic emboli, septic shock, recurrent infection, and/or avascular necrosis (22% vs. 6%).

MRSA patients also were more often admitted to the ICU for further treatment.

Patients included in this series – the largest known case series of children and adolescents presenting with culture-positive S. aureus osteomyelitis and/or septic arthritis – were consecutive patients with positive cultures of blood, bone, or joint aspirate. Those with postoperative and chronic infections were excluded in an effort to minimize bias caused by nosocomial infections, Mr. Sarkissian noted.

The findings support the ongoing concern that MRSA is evolving and becoming more virulent and invasive over time, compared with MSSA infections. In addition, the findings underscore the need for prompt recognition and aggressive treatment of MRSA musculoskeletal infections, as early recognition is paramount for avoiding sequelae and improving patient outcomes.

"A high index of suspicion is still necessary in the setting of musculoskeletal infections in pediatric patients. Multidisciplinary care provides the most successful opportunity for having improved patient outcomes, and this requires employing broad spectrum antibiotic coverage, using aggressive surgical management, and having an awareness of potential complications," Mr. Sarkissian said.

While clinical prediction models have been developed to help in detecting MRSA infections, outcomes using the models have varied geographically, suggesting that there are unknown regional differences among MRSA cases. It remains to be seen whether available models will be useful for identifying MRSA at presentation, he said.

Mr. Sarkissian reported having no disclosures.

ORLANDO – The proportion of pediatric musculoskeletal infections involving methicillin-resistant Staphylococcus aureus vs. methicillin-sensitive S. aureus has increased dramatically over the past decade, according to a retrospective review of cases.

Between 2001 and 2010, 148 patients at the Children’s Hospital of Philadelphia presented with acute musculoskeletal S. aureus infection, and overall, 37 of those involved methicillin-resistant S. aureus (MRSA), Eric Sarkissian reported at the annual meeting of the American Academy of Pediatrics conference.

The proportion of musculoskeletal cases involving MRSA increased from 12% in 2001-2002 to about 35% in 2010, said Mr. Sarkissian, a 4th-year medical student at Drexel University, Philadelphia.

"Furthermore, we found that MRSA infections were associated with a significantly more complicated hospital stay," Mr. Sarkissian said.

Courtesy Janice Haney Carr/CDC

MRSA and methicillin-sensitive S. aureus (MSSA) patients were undergoing magnetic resonance imaging at similar rates, but the average duration of hospitalization was longer for the MRSA patients (13 vs. 8 days), and more MRSA patients required multiple surgical procedures (38% vs. 15%), he said.

In addition, mean presenting C-reactive protein levels were higher in the MRSA vs. MSSA patients (14.7 mg/L vs. 9.8 mg/L), as were infection-related complications, including deep vein thrombosis, septic emboli, septic shock, recurrent infection, and/or avascular necrosis (22% vs. 6%).

MRSA patients also were more often admitted to the ICU for further treatment.

Patients included in this series – the largest known case series of children and adolescents presenting with culture-positive S. aureus osteomyelitis and/or septic arthritis – were consecutive patients with positive cultures of blood, bone, or joint aspirate. Those with postoperative and chronic infections were excluded in an effort to minimize bias caused by nosocomial infections, Mr. Sarkissian noted.

The findings support the ongoing concern that MRSA is evolving and becoming more virulent and invasive over time, compared with MSSA infections. In addition, the findings underscore the need for prompt recognition and aggressive treatment of MRSA musculoskeletal infections, as early recognition is paramount for avoiding sequelae and improving patient outcomes.

"A high index of suspicion is still necessary in the setting of musculoskeletal infections in pediatric patients. Multidisciplinary care provides the most successful opportunity for having improved patient outcomes, and this requires employing broad spectrum antibiotic coverage, using aggressive surgical management, and having an awareness of potential complications," Mr. Sarkissian said.

While clinical prediction models have been developed to help in detecting MRSA infections, outcomes using the models have varied geographically, suggesting that there are unknown regional differences among MRSA cases. It remains to be seen whether available models will be useful for identifying MRSA at presentation, he said.

Mr. Sarkissian reported having no disclosures.

ORLANDO – Maternal smoking has been associated with a number of serious respiratory and nonrespiratory infectious outcomes in infants, according to findings from two large case-control analyses.

Among 47,404 infants hospitalized for an infectious disease within 1 year of birth and 48,233 controls, and among 627 infants who died within 1 year of birth and 2,730 controls, maternal smoking was associated with both hospitalization because of to any infectious disease and mortality from any infectious disease (adjusted odds ratios, 1.52 and 1.51, respectively), Dr. Susanne Tanski of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., reported at the annual meeting of the American Academy of Pediatrics.

© Jasmin Merdan - Fotolia.com

Maternal smoking was associated with hospitalization due to a broad range of infectious diseases, including both respiratory and nonrespiratory diseases (adjusted OR, 1.69 and 1.27, respectively), said Dr. Tanski, who reported the findings of the subgroup analyses on behalf of lead study author Michael Metzger, Ph.D., and coauthor Dr. Abigail Halperin, both of the University of Washington, Seattle.

Stratification by birth weight and gestational age did not appreciably affect the findings with respect to morbidity risk in the infants of smoking mothers, which was found to be independent of both birth weight and gestational age. Mortality risk was found to be independent of gestational age, but the association among low birth weight infants was attenuated.

Even so, if an infant whose mother smoked was of normal weight and gestational age, exposure to maternal smoking appeared to carry an increased risk of infection as well as infectious disease mortality, Dr. Halperin said in an interview.

Included in the study were infants born in Washington from 1987 to 2004. The investigators reviewed linked birth certificate, death certificate, and hospital discharge records.

"We’ve known for a long time that babies born to mothers who smoke during pregnancy are at high risk for serious medical problems relating to low birth weight, premature delivery, and poor lung development, and while we have recognized respiratory infections as a common cause of these sometimes life-threatening infections, this study demonstrates that in utero exposure to smoke increases the risk of hospitalization and death from a much broader range of infections than previously documented," Dr. Halperin said.

She noted that the study was published earlier this year (Pediatr. Infect. Dis. 2013;32:e1-7 [doi:10.1097/INF.0b013e3182704bb5]) but received little notice. When the AAP invited her to submit an abstract for presentation at the conference, she said she was pleased to find that the paper was "selected for this honor."

"I’m very happy it’s receiving some attention now, because it is important to get this information out there so we can try to do something about it. We found that there was a dose-response effect related to number of cigarettes smoked per day, whereby smoking fewer cigarettes significantly lowered the risk for hospitalization," she said.

Thus, counseling pregnant women to reduce their smoking, even if they are not able to quit completely, may help reduce the impact of maternal smoking on infant outcomes, she said.

"Clinicians can help their patients stop smoking by providing nonjudgmental, positively framed advice to quit, and should strongly encourage pregnant women to quit smoking, both for their own health and for the health of their babies," she said, noting that women also should be counseled about the importance of protecting their children from secondhand smoke after birth, as secondhand smoke exposure increases the risk for many of the same infections seen in babies exposed in utero.

Evidence-based treatment, including counseling and approved cessation medication, should be offered to all patients who want to quit, regardless of whether or not they are pregnant, she added.

Dr. Tanski reported a having a patent pending and receiving royalties for a smoke sensor. Dr. Halperin and Mr. Metzger reported having no disclosures.

ORLANDO – Maternal smoking has been associated with a number of serious respiratory and nonrespiratory infectious outcomes in infants, according to findings from two large case-control analyses.

Among 47,404 infants hospitalized for an infectious disease within 1 year of birth and 48,233 controls, and among 627 infants who died within 1 year of birth and 2,730 controls, maternal smoking was associated with both hospitalization because of to any infectious disease and mortality from any infectious disease (adjusted odds ratios, 1.52 and 1.51, respectively), Dr. Susanne Tanski of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., reported at the annual meeting of the American Academy of Pediatrics.

© Jasmin Merdan - Fotolia.com

Maternal smoking was associated with hospitalization due to a broad range of infectious diseases, including both respiratory and nonrespiratory diseases (adjusted OR, 1.69 and 1.27, respectively), said Dr. Tanski, who reported the findings of the subgroup analyses on behalf of lead study author Michael Metzger, Ph.D., and coauthor Dr. Abigail Halperin, both of the University of Washington, Seattle.

Stratification by birth weight and gestational age did not appreciably affect the findings with respect to morbidity risk in the infants of smoking mothers, which was found to be independent of both birth weight and gestational age. Mortality risk was found to be independent of gestational age, but the association among low birth weight infants was attenuated.

Even so, if an infant whose mother smoked was of normal weight and gestational age, exposure to maternal smoking appeared to carry an increased risk of infection as well as infectious disease mortality, Dr. Halperin said in an interview.

Included in the study were infants born in Washington from 1987 to 2004. The investigators reviewed linked birth certificate, death certificate, and hospital discharge records.

"We’ve known for a long time that babies born to mothers who smoke during pregnancy are at high risk for serious medical problems relating to low birth weight, premature delivery, and poor lung development, and while we have recognized respiratory infections as a common cause of these sometimes life-threatening infections, this study demonstrates that in utero exposure to smoke increases the risk of hospitalization and death from a much broader range of infections than previously documented," Dr. Halperin said.

She noted that the study was published earlier this year (Pediatr. Infect. Dis. 2013;32:e1-7 [doi:10.1097/INF.0b013e3182704bb5]) but received little notice. When the AAP invited her to submit an abstract for presentation at the conference, she said she was pleased to find that the paper was "selected for this honor."

"I’m very happy it’s receiving some attention now, because it is important to get this information out there so we can try to do something about it. We found that there was a dose-response effect related to number of cigarettes smoked per day, whereby smoking fewer cigarettes significantly lowered the risk for hospitalization," she said.

Thus, counseling pregnant women to reduce their smoking, even if they are not able to quit completely, may help reduce the impact of maternal smoking on infant outcomes, she said.

"Clinicians can help their patients stop smoking by providing nonjudgmental, positively framed advice to quit, and should strongly encourage pregnant women to quit smoking, both for their own health and for the health of their babies," she said, noting that women also should be counseled about the importance of protecting their children from secondhand smoke after birth, as secondhand smoke exposure increases the risk for many of the same infections seen in babies exposed in utero.

Evidence-based treatment, including counseling and approved cessation medication, should be offered to all patients who want to quit, regardless of whether or not they are pregnant, she added.

Dr. Tanski reported a having a patent pending and receiving royalties for a smoke sensor. Dr. Halperin and Mr. Metzger reported having no disclosures.

ORLANDO – Maternal smoking has been associated with a number of serious respiratory and nonrespiratory infectious outcomes in infants, according to findings from two large case-control analyses.

Among 47,404 infants hospitalized for an infectious disease within 1 year of birth and 48,233 controls, and among 627 infants who died within 1 year of birth and 2,730 controls, maternal smoking was associated with both hospitalization because of to any infectious disease and mortality from any infectious disease (adjusted odds ratios, 1.52 and 1.51, respectively), Dr. Susanne Tanski of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., reported at the annual meeting of the American Academy of Pediatrics.

© Jasmin Merdan - Fotolia.com

Maternal smoking was associated with hospitalization due to a broad range of infectious diseases, including both respiratory and nonrespiratory diseases (adjusted OR, 1.69 and 1.27, respectively), said Dr. Tanski, who reported the findings of the subgroup analyses on behalf of lead study author Michael Metzger, Ph.D., and coauthor Dr. Abigail Halperin, both of the University of Washington, Seattle.

Stratification by birth weight and gestational age did not appreciably affect the findings with respect to morbidity risk in the infants of smoking mothers, which was found to be independent of both birth weight and gestational age. Mortality risk was found to be independent of gestational age, but the association among low birth weight infants was attenuated.

Even so, if an infant whose mother smoked was of normal weight and gestational age, exposure to maternal smoking appeared to carry an increased risk of infection as well as infectious disease mortality, Dr. Halperin said in an interview.

Included in the study were infants born in Washington from 1987 to 2004. The investigators reviewed linked birth certificate, death certificate, and hospital discharge records.

"We’ve known for a long time that babies born to mothers who smoke during pregnancy are at high risk for serious medical problems relating to low birth weight, premature delivery, and poor lung development, and while we have recognized respiratory infections as a common cause of these sometimes life-threatening infections, this study demonstrates that in utero exposure to smoke increases the risk of hospitalization and death from a much broader range of infections than previously documented," Dr. Halperin said.

She noted that the study was published earlier this year (Pediatr. Infect. Dis. 2013;32:e1-7 [doi:10.1097/INF.0b013e3182704bb5]) but received little notice. When the AAP invited her to submit an abstract for presentation at the conference, she said she was pleased to find that the paper was "selected for this honor."

"I’m very happy it’s receiving some attention now, because it is important to get this information out there so we can try to do something about it. We found that there was a dose-response effect related to number of cigarettes smoked per day, whereby smoking fewer cigarettes significantly lowered the risk for hospitalization," she said.

Thus, counseling pregnant women to reduce their smoking, even if they are not able to quit completely, may help reduce the impact of maternal smoking on infant outcomes, she said.

"Clinicians can help their patients stop smoking by providing nonjudgmental, positively framed advice to quit, and should strongly encourage pregnant women to quit smoking, both for their own health and for the health of their babies," she said, noting that women also should be counseled about the importance of protecting their children from secondhand smoke after birth, as secondhand smoke exposure increases the risk for many of the same infections seen in babies exposed in utero.

Evidence-based treatment, including counseling and approved cessation medication, should be offered to all patients who want to quit, regardless of whether or not they are pregnant, she added.

Dr. Tanski reported a having a patent pending and receiving royalties for a smoke sensor. Dr. Halperin and Mr. Metzger reported having no disclosures.

ORLANDO – The popularity of powerful neodymium magnets has led to an increase in magnet ingestion–related injuries among young children, especially in recent years.

Of 2,700 ingestion injuries requiring admission or procedural intervention in children aged 0-18 years between April 1, 2001 and Dec. 21, 2012, 94 were ingestions of these "supermagnets," and, although the first such report was in 2004, a significant increase in both single and multiple magnet ingestion occurred over time. The largest increase involved multiple magnet ingestion in the last 3 years of the study, Dr. Daniel Rosenfield of the University of Toronto reported at the annual meeting of the American Academy of Pediatrics.

The ingestion of multiple magnets can be particularly dangerous, because the magnets – neodymium-iron-boron magnets that are 10-20 times stronger than traditional magnets – can link through loops of bowel and cause pressure necrosis.

"Without prompt recognition of multiple-magnet ingestion, bowel perforation, sepsis, and death can result," he said.

In fact, in this case series, 6 patients underwent surgical removal of the magnets and 10 underwent endoscopic removal. No deaths were reported, Dr. Rosenfield said.

The cases involved patients seen at the Hospital for Sick Children in Toronto. The patients ranged in age from 7 months to 13 years, with a mean age of 4.5 years. Most (65%) were boys.

Ingestion of up to 34 of the tiny magnets – which may look like candy to children – has been reported.

The findings confirm what physicians at the Hospital for Sick Children have suspected: that the ingestion of these dangerous toys has been increasing, with a spike in incidence over the past 3 years, Dr. Rosenfield said.

"What we’re seeing is really an epidemic driven by a new technology," he added.

Supermagnets came into the market in the early 2000s in toys, jewelry, and other novelty items, and they surged in popularity in the late 2000s when they were marketed in the form of novelty desk toys for adults. In the wake of several cases involving multiple magnet ingestion that resulted in a number of cases of pediatric bowel perforation, sepsis, and one death, the U.S. Consumer Product Safety Commission began work in 2012 to set industry safety standards and sought to remove certain supermagnet desk toys from the market. Canada also recently implemented a mandatory recall of some of the products and banned their sale, Dr. Rosenfield said.

He applauded the strong stance and action with respect to removing the products from the market but noted that the magnets can still be found in products sold before the recall, raising concerns that ingestion injuries will continue to occur.

Thus, clinicians should be aware of the risk of magnet ingestions and of the potential morbidity associated with ingestion, as well as with the appropriate management of patients who ingest the magnets. Furthermore, given data suggesting that many pediatricians are unaware of the dangers, health organizations should spread the word to physicians, parents, teachers, and the general public about the dangers to help assure that the magnets will be kept away from children, he said.

"These new magnets are vastly more powerful, smaller in size, and seem innocuous – parents just aren’t aware of the potential danger," he said.

Dr. Rosenfield reported having no disclosures.

ORLANDO – The popularity of powerful neodymium magnets has led to an increase in magnet ingestion–related injuries among young children, especially in recent years.

Of 2,700 ingestion injuries requiring admission or procedural intervention in children aged 0-18 years between April 1, 2001 and Dec. 21, 2012, 94 were ingestions of these "supermagnets," and, although the first such report was in 2004, a significant increase in both single and multiple magnet ingestion occurred over time. The largest increase involved multiple magnet ingestion in the last 3 years of the study, Dr. Daniel Rosenfield of the University of Toronto reported at the annual meeting of the American Academy of Pediatrics.

The ingestion of multiple magnets can be particularly dangerous, because the magnets – neodymium-iron-boron magnets that are 10-20 times stronger than traditional magnets – can link through loops of bowel and cause pressure necrosis.

"Without prompt recognition of multiple-magnet ingestion, bowel perforation, sepsis, and death can result," he said.

In fact, in this case series, 6 patients underwent surgical removal of the magnets and 10 underwent endoscopic removal. No deaths were reported, Dr. Rosenfield said.

The cases involved patients seen at the Hospital for Sick Children in Toronto. The patients ranged in age from 7 months to 13 years, with a mean age of 4.5 years. Most (65%) were boys.

Ingestion of up to 34 of the tiny magnets – which may look like candy to children – has been reported.

The findings confirm what physicians at the Hospital for Sick Children have suspected: that the ingestion of these dangerous toys has been increasing, with a spike in incidence over the past 3 years, Dr. Rosenfield said.

"What we’re seeing is really an epidemic driven by a new technology," he added.

Supermagnets came into the market in the early 2000s in toys, jewelry, and other novelty items, and they surged in popularity in the late 2000s when they were marketed in the form of novelty desk toys for adults. In the wake of several cases involving multiple magnet ingestion that resulted in a number of cases of pediatric bowel perforation, sepsis, and one death, the U.S. Consumer Product Safety Commission began work in 2012 to set industry safety standards and sought to remove certain supermagnet desk toys from the market. Canada also recently implemented a mandatory recall of some of the products and banned their sale, Dr. Rosenfield said.

He applauded the strong stance and action with respect to removing the products from the market but noted that the magnets can still be found in products sold before the recall, raising concerns that ingestion injuries will continue to occur.

Thus, clinicians should be aware of the risk of magnet ingestions and of the potential morbidity associated with ingestion, as well as with the appropriate management of patients who ingest the magnets. Furthermore, given data suggesting that many pediatricians are unaware of the dangers, health organizations should spread the word to physicians, parents, teachers, and the general public about the dangers to help assure that the magnets will be kept away from children, he said.

"These new magnets are vastly more powerful, smaller in size, and seem innocuous – parents just aren’t aware of the potential danger," he said.

Dr. Rosenfield reported having no disclosures.

ORLANDO – The popularity of powerful neodymium magnets has led to an increase in magnet ingestion–related injuries among young children, especially in recent years.

Of 2,700 ingestion injuries requiring admission or procedural intervention in children aged 0-18 years between April 1, 2001 and Dec. 21, 2012, 94 were ingestions of these "supermagnets," and, although the first such report was in 2004, a significant increase in both single and multiple magnet ingestion occurred over time. The largest increase involved multiple magnet ingestion in the last 3 years of the study, Dr. Daniel Rosenfield of the University of Toronto reported at the annual meeting of the American Academy of Pediatrics.

The ingestion of multiple magnets can be particularly dangerous, because the magnets – neodymium-iron-boron magnets that are 10-20 times stronger than traditional magnets – can link through loops of bowel and cause pressure necrosis.

"Without prompt recognition of multiple-magnet ingestion, bowel perforation, sepsis, and death can result," he said.

In fact, in this case series, 6 patients underwent surgical removal of the magnets and 10 underwent endoscopic removal. No deaths were reported, Dr. Rosenfield said.

The cases involved patients seen at the Hospital for Sick Children in Toronto. The patients ranged in age from 7 months to 13 years, with a mean age of 4.5 years. Most (65%) were boys.

Ingestion of up to 34 of the tiny magnets – which may look like candy to children – has been reported.

The findings confirm what physicians at the Hospital for Sick Children have suspected: that the ingestion of these dangerous toys has been increasing, with a spike in incidence over the past 3 years, Dr. Rosenfield said.

"What we’re seeing is really an epidemic driven by a new technology," he added.

Supermagnets came into the market in the early 2000s in toys, jewelry, and other novelty items, and they surged in popularity in the late 2000s when they were marketed in the form of novelty desk toys for adults. In the wake of several cases involving multiple magnet ingestion that resulted in a number of cases of pediatric bowel perforation, sepsis, and one death, the U.S. Consumer Product Safety Commission began work in 2012 to set industry safety standards and sought to remove certain supermagnet desk toys from the market. Canada also recently implemented a mandatory recall of some of the products and banned their sale, Dr. Rosenfield said.

He applauded the strong stance and action with respect to removing the products from the market but noted that the magnets can still be found in products sold before the recall, raising concerns that ingestion injuries will continue to occur.

Thus, clinicians should be aware of the risk of magnet ingestions and of the potential morbidity associated with ingestion, as well as with the appropriate management of patients who ingest the magnets. Furthermore, given data suggesting that many pediatricians are unaware of the dangers, health organizations should spread the word to physicians, parents, teachers, and the general public about the dangers to help assure that the magnets will be kept away from children, he said.

"These new magnets are vastly more powerful, smaller in size, and seem innocuous – parents just aren’t aware of the potential danger," he said.

Dr. Rosenfield reported having no disclosures.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – Centralized pain or sensitization occurs in most patients with fibromyalgia and can be identified in 20%-30% of patients with other pain states, such as rheumatoid arthritis, lupus, low back pain, and osteoarthritis, according to Dr. Daniel J. Clauw.

This has implications for both diagnosis and treatment of these conditions. However, current paradigms for diagnosis and treatment are antiquated, Dr. Clauw, professor of anesthesiology and medicine, and director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor, said at the annual Perspectives in Rheumatic Diseases conference.

There is no chronic pain state in which the degree of damage or inflammation in the periphery correlates well with the level of pain the patient experiences, and yet, existing diagnostic paradigms – as well as the terms used to describe chronic pain states – imply otherwise, he explained.

In fact, until recently it was typically assumed that when a disparity between peripheral findings and pain existed, the problem was a psychological one, he said.

In reality, there are numerous nonpsychological neurobiologic factors that affect pain sensitivity, and these are operative in many chronic pain states. Thus, it is imperative that the diagnostic and therapeutic paradigms be modified to better identify and treat "central pain," he said.

Centralized pain is pain in which the spinal cord and/or brain play a much bigger role than the peripheral nervous system. In patients with centralized pain, the pain is more associated with pain processing pathways than with "peripheral nociceptive input out at the periphery that you will make better with nonsteroidal anti-inflammatory drugs, opioids, and surgical procedures," Dr. Clauw said.

"The problem is the diseases don’t tell us which pain state someone has," he added.

Certain clinical characteristics can provide clues, however. Among them are multifocal pain, use of neuropathic verbal descriptors of pain, higher current and lifetime history of pain, the presence of multiple other somatic symptoms, and sensitivity to multiple sensory stimuli.

"When someone centralizes their pain, they don’t have just pain any more, they have a lot of other central nervous system symptoms that are also coming from the brain, including fatigue, memory problems, sleep disturbances," he said, noting that when a patient presents with multifocal pain accompanied by these other symptoms, this should be "a blinking neon light that this person has centralized their pain."

Additionally, patients with centralized pain have a wide continuum of pain, may experience exacerbation because of stressors, and may have a generally normal physical examination except for diffuse tenderness and nonspecific neurologic signs. This type of pain is 1.5 to 2 times more common in women than men and has strong genetic underpinnings, so a family history can be helpful in identifying patients with centralized pain, Dr. Clauw noted.

Studies suggest that a number of genes that may be involved in the process, including the gene encoding catecholamine-O-methyltransferase (COMT), certain alleles of which are associated with a threefold increased risk of developing different types of chronic pain conditions, he said.

A number of pharmacologic agents have been studied for central pain; the strongest evidence exists for dual reuptake inhibitors (including tricyclic compounds, selective-norepinephrine reuptake inhibitors, and norepinephrine-selective reuptake inhibitors), and the anticonvulsants gabapentin and pregabalin. Modest evidence exists for tramadol, older less-selective selective-serotonin reuptake inhibitors, gamma-hydroxybutyrate, and low-dose naltrexone. Weak evidence suggests a benefit with cannabinoids (although evidence of benefit is increasing), growth hormone, 5-hydroxytryptamine, tropisetron, S-adenosyl-L-methionine. There is no evidence with respect to opioids, corticosteroids, nonsteroidal antiinflammatory drugs, benzodiazepine and nonbenzodiazepine hypnotics, and guaifenesin.

None of the available pharmacologic agents have anything more than modest efficacy when used as stand-alone therapy, he said, stressing the importance of also using nonpharmacologic therapies in patients with centralized pain.

The nonpharmacologic options are similar for any chronic pain state, Dr. Clauw said, noting that strong evidence exists for education, aerobic exercise, and cognitive-behavior therapy. Modest evidence exists for strength training, hypnotherapy, biofeedback, balneotherapy, yoga, and tai chi. Weak evidence suggests a possible benefit with acupuncture, chiropractic therapy, manual and massage therapy, electrotherapy, and ultrasound. No evidence exists for trigger point injections and flexibility exercise.

Many of the particularly useful nonpharmacologic therapies, including cognitive-behavior therapy or exercise, are rarely used in clinical practice, he noted.

An approach known as the ExPRESS approach to chronic pain can help improve outcomes by addressing the various factors involved in centralized pain. ExPRESS stands for exercise, psychiatric comorbidity, regaining function, education, sleep hygiene, and stress management, he said.

The approach was proposed by Afton L. Hassett, Psy.D., and Richard N. Gevirtz, Ph.D., in a 2009 study (Rheum. Dis. Clin. North Am. 2009;35:393-407), which stresses the importance of providing comprehensive care for patients with chronic pain by addressing each of these interrelated factors.

It doesn’t matter where the pain is coming from. Long-term pain increases stress levels, decreases sleep and exercise, and can lead to social isolation – all things that can make pain worse. Thus, a change in the "volume control" of the central nervous system isn’t necessarily to blame when a patient experiences worsening over time, rather it may be the accumulation of these other factors, he said at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

"Unless and until you treat these patients with exercise, education, and cognitive-behavioral therapy ... you’re not going to make chronic pain patients better, and you’re certainly not going to make centralized pain patients better unless you aggressively use [these tools]," he said.

Dr. Clauw has been a consultant for Merck, UCB, Cypress Biosciences, Eli Lilly, Jazz Pharmaceuticals, Pierre Fabre Pharmaceuticals, Pfizer, Nuvo Research, and Forest Laboratories, and has received grant support from Nuvo Research and Forest Laboratories.

LAS VEGAS – The use of an alternative anti–tumor necrosis factor drug is not necessarily precluded in a psoriasis patient with both skin and joint symptoms who has failed two previous anti-TNF drugs, according to Dr. Kenneth B. Gordon.

Dr. Gordon, professor of dermatology at Northwestern University, Chicago, described a case involving a 52-year-old man with a 20-year history of psoriasis who initially presented with mainly scalp and limited plaque psoriasis, and who was treated with topical corticosteroids and topical calcipotriene. After developing more extensive disease, he was treated successfully with ultraviolet B phototherapy.

Eleven years after first presenting with psoriasis, he presented with peripheral arthritis and enthesitis and was diagnosed with psoriatic arthritis.

The patient was treated initially with sulfasalazine, but failed to respond; methotrexate had only modest benefit, and at higher doses the patient developed liver function test abnormalities due to steatohepatitis, Dr. Gordon said at Perspectives in Rheumatic Diseases 2013.

Etanercept was initiated at 50 mg twice weekly, and the patient had an excellent initial response.

However, after stepping down to 50 mg weekly, his psoriasis flared.

"His joints were doing fine, but his skin was getting bad," Dr. Gordon said, noting that this type of response was also seen in early studies of etanercept, which showed that when doses were reduced to 50 mg weekly after 12 weeks, responses leveled off, with some patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) 75 response, and some losing PASI 75 response.

"It turns out that this occurs in 20%-30% of patients," he said, adding that some controversy exists regarding dosing, because "it’s not entirely clear that if you had just started at the lower dose and just let them go at the 50 mg once a week, that at 6 months they’d be any different than if you gave them the higher dose initially."

The REVEAL study of adalimumab for psoriasis also demonstrated loss of response after 33 weeks among those with an initial PASI 75 response (J. Am. Acad. Dermatol. 2012;66:241-51), he said.

"So clearly, patients lose response. Now, that lessens over time, but in the first year in psoriasis – and my guess is, in psoriatic arthritis as well – you have loss of effect at a relatively high level with all of these medicines," he said.

In fact, in the patient Dr. Gordon presented, a switch to adalimumab at a dose of 40 mg every other week resulted in an excellent initial response in both joints and skin, but skin symptoms returned after 8 months.

"This is something we’re all familiar with – patients doing well on an anti-TNF and then losing effect after a period of time on medication," he said.

So what are the alternatives?

An anti-TNF drug option after the patient cycles through etanercept, adalimumab, and infliximab is certolizumab, which was approved in September for the treatment of psoriatic arthritis. Study data suggest that the drug is "quite effective for psoriasis, was well tolerated, and similar to the other anti-TNFs," he said.

Using certolizumab is a reasonable approach that appears to work for both skin and joint symptoms, he said.

Golimumab is another possible option for treatment, but primary psoriasis data are lacking with this drug.

"It is my feeling that golimumab is probably not as potent for psoriasis as the other anti-TNF agents that we have, but that is an opinion," he said.

As for alternatives to anti-TNF agents, the PHEONIX 2 trial (Lancet 2008;371:1675-84) provided reasonable data in support of the interleukin-12 and -23 monoclonal antibody ustekinumab for skin disease, but patients who failed prior anti-TNF therapy actually had a poorer outcome, so that is something to keep in mind, he said, noting that adding methotrexate may help prevent a flare in patients who are switched from an anti-TNF agent to ustekinumab.

Ustekinumab, which also was approved in September for the treatment of psoriatic arthritis, is likely more useful for the skin, but is not exceptional for joint disease, he said at the meeting, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Apremilast and tofacitinib, drugs now in development for psoriasis, may also prove useful in the future, as they may "theoretically be of benefit" based on currently available data, he said.

Dr. Gordon has received research support and/or honoraria from AbbVie (which markets adalimumab), Amgen (which markets etanercept), Celgene (which is developing apremilast), Eli Lilly, Janssen (which markets golimumab, infliximab, and ustekinumab), Novartis, and Pfizer (which markets tofacitinib).

LAS VEGAS – The use of an alternative anti–tumor necrosis factor drug is not necessarily precluded in a psoriasis patient with both skin and joint symptoms who has failed two previous anti-TNF drugs, according to Dr. Kenneth B. Gordon.

Dr. Gordon, professor of dermatology at Northwestern University, Chicago, described a case involving a 52-year-old man with a 20-year history of psoriasis who initially presented with mainly scalp and limited plaque psoriasis, and who was treated with topical corticosteroids and topical calcipotriene. After developing more extensive disease, he was treated successfully with ultraviolet B phototherapy.

Eleven years after first presenting with psoriasis, he presented with peripheral arthritis and enthesitis and was diagnosed with psoriatic arthritis.

The patient was treated initially with sulfasalazine, but failed to respond; methotrexate had only modest benefit, and at higher doses the patient developed liver function test abnormalities due to steatohepatitis, Dr. Gordon said at Perspectives in Rheumatic Diseases 2013.

Etanercept was initiated at 50 mg twice weekly, and the patient had an excellent initial response.

However, after stepping down to 50 mg weekly, his psoriasis flared.

"His joints were doing fine, but his skin was getting bad," Dr. Gordon said, noting that this type of response was also seen in early studies of etanercept, which showed that when doses were reduced to 50 mg weekly after 12 weeks, responses leveled off, with some patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) 75 response, and some losing PASI 75 response.

"It turns out that this occurs in 20%-30% of patients," he said, adding that some controversy exists regarding dosing, because "it’s not entirely clear that if you had just started at the lower dose and just let them go at the 50 mg once a week, that at 6 months they’d be any different than if you gave them the higher dose initially."

The REVEAL study of adalimumab for psoriasis also demonstrated loss of response after 33 weeks among those with an initial PASI 75 response (J. Am. Acad. Dermatol. 2012;66:241-51), he said.

"So clearly, patients lose response. Now, that lessens over time, but in the first year in psoriasis – and my guess is, in psoriatic arthritis as well – you have loss of effect at a relatively high level with all of these medicines," he said.

In fact, in the patient Dr. Gordon presented, a switch to adalimumab at a dose of 40 mg every other week resulted in an excellent initial response in both joints and skin, but skin symptoms returned after 8 months.

"This is something we’re all familiar with – patients doing well on an anti-TNF and then losing effect after a period of time on medication," he said.

So what are the alternatives?

An anti-TNF drug option after the patient cycles through etanercept, adalimumab, and infliximab is certolizumab, which was approved in September for the treatment of psoriatic arthritis. Study data suggest that the drug is "quite effective for psoriasis, was well tolerated, and similar to the other anti-TNFs," he said.

Using certolizumab is a reasonable approach that appears to work for both skin and joint symptoms, he said.

Golimumab is another possible option for treatment, but primary psoriasis data are lacking with this drug.

"It is my feeling that golimumab is probably not as potent for psoriasis as the other anti-TNF agents that we have, but that is an opinion," he said.

As for alternatives to anti-TNF agents, the PHEONIX 2 trial (Lancet 2008;371:1675-84) provided reasonable data in support of the interleukin-12 and -23 monoclonal antibody ustekinumab for skin disease, but patients who failed prior anti-TNF therapy actually had a poorer outcome, so that is something to keep in mind, he said, noting that adding methotrexate may help prevent a flare in patients who are switched from an anti-TNF agent to ustekinumab.

Ustekinumab, which also was approved in September for the treatment of psoriatic arthritis, is likely more useful for the skin, but is not exceptional for joint disease, he said at the meeting, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Apremilast and tofacitinib, drugs now in development for psoriasis, may also prove useful in the future, as they may "theoretically be of benefit" based on currently available data, he said.

Dr. Gordon has received research support and/or honoraria from AbbVie (which markets adalimumab), Amgen (which markets etanercept), Celgene (which is developing apremilast), Eli Lilly, Janssen (which markets golimumab, infliximab, and ustekinumab), Novartis, and Pfizer (which markets tofacitinib).

LAS VEGAS – The use of an alternative anti–tumor necrosis factor drug is not necessarily precluded in a psoriasis patient with both skin and joint symptoms who has failed two previous anti-TNF drugs, according to Dr. Kenneth B. Gordon.

Dr. Gordon, professor of dermatology at Northwestern University, Chicago, described a case involving a 52-year-old man with a 20-year history of psoriasis who initially presented with mainly scalp and limited plaque psoriasis, and who was treated with topical corticosteroids and topical calcipotriene. After developing more extensive disease, he was treated successfully with ultraviolet B phototherapy.

Eleven years after first presenting with psoriasis, he presented with peripheral arthritis and enthesitis and was diagnosed with psoriatic arthritis.

The patient was treated initially with sulfasalazine, but failed to respond; methotrexate had only modest benefit, and at higher doses the patient developed liver function test abnormalities due to steatohepatitis, Dr. Gordon said at Perspectives in Rheumatic Diseases 2013.

Etanercept was initiated at 50 mg twice weekly, and the patient had an excellent initial response.

However, after stepping down to 50 mg weekly, his psoriasis flared.

"His joints were doing fine, but his skin was getting bad," Dr. Gordon said, noting that this type of response was also seen in early studies of etanercept, which showed that when doses were reduced to 50 mg weekly after 12 weeks, responses leveled off, with some patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) 75 response, and some losing PASI 75 response.

"It turns out that this occurs in 20%-30% of patients," he said, adding that some controversy exists regarding dosing, because "it’s not entirely clear that if you had just started at the lower dose and just let them go at the 50 mg once a week, that at 6 months they’d be any different than if you gave them the higher dose initially."

The REVEAL study of adalimumab for psoriasis also demonstrated loss of response after 33 weeks among those with an initial PASI 75 response (J. Am. Acad. Dermatol. 2012;66:241-51), he said.

"So clearly, patients lose response. Now, that lessens over time, but in the first year in psoriasis – and my guess is, in psoriatic arthritis as well – you have loss of effect at a relatively high level with all of these medicines," he said.

In fact, in the patient Dr. Gordon presented, a switch to adalimumab at a dose of 40 mg every other week resulted in an excellent initial response in both joints and skin, but skin symptoms returned after 8 months.

"This is something we’re all familiar with – patients doing well on an anti-TNF and then losing effect after a period of time on medication," he said.

So what are the alternatives?

An anti-TNF drug option after the patient cycles through etanercept, adalimumab, and infliximab is certolizumab, which was approved in September for the treatment of psoriatic arthritis. Study data suggest that the drug is "quite effective for psoriasis, was well tolerated, and similar to the other anti-TNFs," he said.

Using certolizumab is a reasonable approach that appears to work for both skin and joint symptoms, he said.

Golimumab is another possible option for treatment, but primary psoriasis data are lacking with this drug.

"It is my feeling that golimumab is probably not as potent for psoriasis as the other anti-TNF agents that we have, but that is an opinion," he said.

As for alternatives to anti-TNF agents, the PHEONIX 2 trial (Lancet 2008;371:1675-84) provided reasonable data in support of the interleukin-12 and -23 monoclonal antibody ustekinumab for skin disease, but patients who failed prior anti-TNF therapy actually had a poorer outcome, so that is something to keep in mind, he said, noting that adding methotrexate may help prevent a flare in patients who are switched from an anti-TNF agent to ustekinumab.

Ustekinumab, which also was approved in September for the treatment of psoriatic arthritis, is likely more useful for the skin, but is not exceptional for joint disease, he said at the meeting, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Apremilast and tofacitinib, drugs now in development for psoriasis, may also prove useful in the future, as they may "theoretically be of benefit" based on currently available data, he said.

Dr. Gordon has received research support and/or honoraria from AbbVie (which markets adalimumab), Amgen (which markets etanercept), Celgene (which is developing apremilast), Eli Lilly, Janssen (which markets golimumab, infliximab, and ustekinumab), Novartis, and Pfizer (which markets tofacitinib).

LAS VEGAS – Scleroderma patients are at particularly high risk for developing pulmonary arterial hypertension, but treatment options are expanding, and with early referral to a PAH specialist, outcomes can be improved, according to Dr. Ronald J. Oudiz.

"In 1995 we had nothing. Now we have nine treatments specifically for PAH, and more that are being looked at," he said at Perspectives in Rheumatic Diseases 2013.

Three major signaling pathways, including the prostacyclin, endothelin, and nitric oxide pathways, form the basis for the available treatment options for this progressive and deadly disease, which has a 36-month survival rate of only about 60%. The treatments include prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE-5) inhibitors, said Dr. Oudiz, professor of medicine at the University of California, Los Angeles, and director of the Liu Center for Pulmonary Hypertension at Harbor-UCLA Medical Center.

The prostacyclin analogues include intravenous epoprostenol, inhaled iloprost, and treprostinil, which can be inhaled or delivered intravenously or subcutaneously. These have been shown to improve performance on the 6-minute walk test in a dose-dependent fashion, Dr. Oudiz noted.

Side effects with prostacyclin analogues can include flushing, headache, rash, thrombocytopenia, infection, and gastrointestinal effects such as diarrhea, nausea, and weight loss.

The endothelin receptor antagonists include bosentan and ambrisentan, which both are delivered orally. Their approval was "revolutionary, because for a while we only had IV drugs," he said.

Side effects with endothelin receptor antagonists include liver function test abnormalities, headache, nasal congestion, and edema. Although these drugs are generally tolerated well, liver function test abnormalities and edema can be troublesome for both patients and physicians as they require close monitoring and dose modification or interruption, he said.

PDE-5 inhibitors include sildenafil and tadalafil, which also are both oral drugs, and which have side effects that are similar to those seen with the endothelin-receptor antagonists, with the addition of myalgia, diarrhea, dyspepsia, and nose bleeds, he noted.

Overall, studies suggest that treatment with PAH drugs not only leads to improved exercise capacity, but probably improves long-term survival. In a meta-analysis of several major PAH drug trials, the majority of studies showed a potential mortality benefit (Eur. Heart. J. 2009;30:394-403), Dr. Oudiz noted.

"I say potential because we know none of the studies assessed in the meta-analysis were powered to examine mortality ... but nevertheless, we believe we’re doing more than just improving exercise capacity," he said.

In fact, in a study published in August in the New England Journal of Medicine, the new endothelin receptor antagonist macitentan was associated with a dose-dependent decrease in the number of outcome events measured, relative to placebo, including death, transplant, and heart failure in patients with PAH, he noted (N. Engl. J. Med. 2013;369:809-18).

"These are some really important endpoints we’re finally starting to meet," he said.

These advances underscore the importance of increased awareness of the risk of PAH in scleroderma and early recognition of the condition, and – since diagnosis and the subtleties of management are complex – they also underscore the importance of early referral to a PAH specialist, he said.

"Early treatment is always preferable to later treatment," he concluded at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Dr. Oudiz has received grant or research support from, served as a consultant to, and/or served on a speakers’ bureau for Actelion, Bayer, Gilead, Ikaria, Lung, Pfizer, and United Therapeutics.

LAS VEGAS – Scleroderma patients are at particularly high risk for developing pulmonary arterial hypertension, but treatment options are expanding, and with early referral to a PAH specialist, outcomes can be improved, according to Dr. Ronald J. Oudiz.

"In 1995 we had nothing. Now we have nine treatments specifically for PAH, and more that are being looked at," he said at Perspectives in Rheumatic Diseases 2013.

Three major signaling pathways, including the prostacyclin, endothelin, and nitric oxide pathways, form the basis for the available treatment options for this progressive and deadly disease, which has a 36-month survival rate of only about 60%. The treatments include prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE-5) inhibitors, said Dr. Oudiz, professor of medicine at the University of California, Los Angeles, and director of the Liu Center for Pulmonary Hypertension at Harbor-UCLA Medical Center.

The prostacyclin analogues include intravenous epoprostenol, inhaled iloprost, and treprostinil, which can be inhaled or delivered intravenously or subcutaneously. These have been shown to improve performance on the 6-minute walk test in a dose-dependent fashion, Dr. Oudiz noted.

Side effects with prostacyclin analogues can include flushing, headache, rash, thrombocytopenia, infection, and gastrointestinal effects such as diarrhea, nausea, and weight loss.

The endothelin receptor antagonists include bosentan and ambrisentan, which both are delivered orally. Their approval was "revolutionary, because for a while we only had IV drugs," he said.

Side effects with endothelin receptor antagonists include liver function test abnormalities, headache, nasal congestion, and edema. Although these drugs are generally tolerated well, liver function test abnormalities and edema can be troublesome for both patients and physicians as they require close monitoring and dose modification or interruption, he said.

PDE-5 inhibitors include sildenafil and tadalafil, which also are both oral drugs, and which have side effects that are similar to those seen with the endothelin-receptor antagonists, with the addition of myalgia, diarrhea, dyspepsia, and nose bleeds, he noted.

Overall, studies suggest that treatment with PAH drugs not only leads to improved exercise capacity, but probably improves long-term survival. In a meta-analysis of several major PAH drug trials, the majority of studies showed a potential mortality benefit (Eur. Heart. J. 2009;30:394-403), Dr. Oudiz noted.

"I say potential because we know none of the studies assessed in the meta-analysis were powered to examine mortality ... but nevertheless, we believe we’re doing more than just improving exercise capacity," he said.

In fact, in a study published in August in the New England Journal of Medicine, the new endothelin receptor antagonist macitentan was associated with a dose-dependent decrease in the number of outcome events measured, relative to placebo, including death, transplant, and heart failure in patients with PAH, he noted (N. Engl. J. Med. 2013;369:809-18).

"These are some really important endpoints we’re finally starting to meet," he said.

These advances underscore the importance of increased awareness of the risk of PAH in scleroderma and early recognition of the condition, and – since diagnosis and the subtleties of management are complex – they also underscore the importance of early referral to a PAH specialist, he said.

"Early treatment is always preferable to later treatment," he concluded at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Dr. Oudiz has received grant or research support from, served as a consultant to, and/or served on a speakers’ bureau for Actelion, Bayer, Gilead, Ikaria, Lung, Pfizer, and United Therapeutics.

LAS VEGAS – Scleroderma patients are at particularly high risk for developing pulmonary arterial hypertension, but treatment options are expanding, and with early referral to a PAH specialist, outcomes can be improved, according to Dr. Ronald J. Oudiz.

"In 1995 we had nothing. Now we have nine treatments specifically for PAH, and more that are being looked at," he said at Perspectives in Rheumatic Diseases 2013.

Three major signaling pathways, including the prostacyclin, endothelin, and nitric oxide pathways, form the basis for the available treatment options for this progressive and deadly disease, which has a 36-month survival rate of only about 60%. The treatments include prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE-5) inhibitors, said Dr. Oudiz, professor of medicine at the University of California, Los Angeles, and director of the Liu Center for Pulmonary Hypertension at Harbor-UCLA Medical Center.

The prostacyclin analogues include intravenous epoprostenol, inhaled iloprost, and treprostinil, which can be inhaled or delivered intravenously or subcutaneously. These have been shown to improve performance on the 6-minute walk test in a dose-dependent fashion, Dr. Oudiz noted.

Side effects with prostacyclin analogues can include flushing, headache, rash, thrombocytopenia, infection, and gastrointestinal effects such as diarrhea, nausea, and weight loss.

The endothelin receptor antagonists include bosentan and ambrisentan, which both are delivered orally. Their approval was "revolutionary, because for a while we only had IV drugs," he said.

Side effects with endothelin receptor antagonists include liver function test abnormalities, headache, nasal congestion, and edema. Although these drugs are generally tolerated well, liver function test abnormalities and edema can be troublesome for both patients and physicians as they require close monitoring and dose modification or interruption, he said.

PDE-5 inhibitors include sildenafil and tadalafil, which also are both oral drugs, and which have side effects that are similar to those seen with the endothelin-receptor antagonists, with the addition of myalgia, diarrhea, dyspepsia, and nose bleeds, he noted.

Overall, studies suggest that treatment with PAH drugs not only leads to improved exercise capacity, but probably improves long-term survival. In a meta-analysis of several major PAH drug trials, the majority of studies showed a potential mortality benefit (Eur. Heart. J. 2009;30:394-403), Dr. Oudiz noted.

"I say potential because we know none of the studies assessed in the meta-analysis were powered to examine mortality ... but nevertheless, we believe we’re doing more than just improving exercise capacity," he said.

In fact, in a study published in August in the New England Journal of Medicine, the new endothelin receptor antagonist macitentan was associated with a dose-dependent decrease in the number of outcome events measured, relative to placebo, including death, transplant, and heart failure in patients with PAH, he noted (N. Engl. J. Med. 2013;369:809-18).

"These are some really important endpoints we’re finally starting to meet," he said.

These advances underscore the importance of increased awareness of the risk of PAH in scleroderma and early recognition of the condition, and – since diagnosis and the subtleties of management are complex – they also underscore the importance of early referral to a PAH specialist, he said.

"Early treatment is always preferable to later treatment," he concluded at the meeting held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

Dr. Oudiz has received grant or research support from, served as a consultant to, and/or served on a speakers’ bureau for Actelion, Bayer, Gilead, Ikaria, Lung, Pfizer, and United Therapeutics.

SAN FRANCISCO – Cefazolin was better tolerated than nafcillin for the outpatient treatment of methicillin-sensitive Staphylococcus aureus among clinic patients included in a retrospective cohort study.

A number of drug-related adverse events occurred more often in 366 patients who received outpatient parenteral antimicrobial therapy (OPAT) with nafcillin, compared with 119 patients treated with cefazolin, including rash (13.9% vs. 4.2%), renal dysfunction (11.4% vs. 3.3%), and transaminitis (8.1% vs. 1.6%), Dr. Ilan Youngster reported at an annual scientific meeting on infectious diseases.

The patients in this study were adults with a mean age of 57 years in the nafcillin group and 56 years in the cefazolin group.

Furthermore, neutropenia developed in 8.4% of nafcillin patients, compared with 3.3% of cefazolin patients, and Clostridium difficile colitis developed in 2.4% vs. 0.8% of the nafcillin and cefazolin patients, respectively, said Dr. Youngster, a research fellow at Boston Children’s Hospital and Massachusetts General Hospital, Boston.

The discontinuation rate was significantly higher in the nafcillin group than in the cefazolin group, with 34% and 7% of patients in the groups, respectively, failing to complete the prespecified treatment course, he said. Nine patients who discontinued nafcillin switched over to cefazolin and completed treatment without any further drug-related adverse events.

The findings have implications for treatment of methicillin-sensitive Staphylococcus aureus (MSSA), which is a major pathogen in both community and health care–acquired infection, and one of the most common infections requiring prolonged antimicrobial administration.

Both nafcillin and cefazolin are considered first-line options for therapy for most MSSA infections, and recent studies suggest that the two beta-lactam antibiotics have similar efficacy, Dr. Youngster explained.

In addition to cost and efficacy, the differences in tolerability between these two drugs should be considered when deciding on long-term intravenous treatment for MSSA in the OPAT setting, he said. A failure to tolerate treatment will result in exposure to a partially treated infection should treatment be discontinued prematurely, or to the inconvenience of returning for another evaluation and a change of treatment.

Although the current study did not compare the efficacy of the two drugs, a clinical data collection system now in place will allow for such assessments going forward, he said.

IDWeek is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Youngster reported having no disclosures.

SAN FRANCISCO – Cefazolin was better tolerated than nafcillin for the outpatient treatment of methicillin-sensitive Staphylococcus aureus among clinic patients included in a retrospective cohort study.

A number of drug-related adverse events occurred more often in 366 patients who received outpatient parenteral antimicrobial therapy (OPAT) with nafcillin, compared with 119 patients treated with cefazolin, including rash (13.9% vs. 4.2%), renal dysfunction (11.4% vs. 3.3%), and transaminitis (8.1% vs. 1.6%), Dr. Ilan Youngster reported at an annual scientific meeting on infectious diseases.

The patients in this study were adults with a mean age of 57 years in the nafcillin group and 56 years in the cefazolin group.

Furthermore, neutropenia developed in 8.4% of nafcillin patients, compared with 3.3% of cefazolin patients, and Clostridium difficile colitis developed in 2.4% vs. 0.8% of the nafcillin and cefazolin patients, respectively, said Dr. Youngster, a research fellow at Boston Children’s Hospital and Massachusetts General Hospital, Boston.

The discontinuation rate was significantly higher in the nafcillin group than in the cefazolin group, with 34% and 7% of patients in the groups, respectively, failing to complete the prespecified treatment course, he said. Nine patients who discontinued nafcillin switched over to cefazolin and completed treatment without any further drug-related adverse events.

The findings have implications for treatment of methicillin-sensitive Staphylococcus aureus (MSSA), which is a major pathogen in both community and health care–acquired infection, and one of the most common infections requiring prolonged antimicrobial administration.

Both nafcillin and cefazolin are considered first-line options for therapy for most MSSA infections, and recent studies suggest that the two beta-lactam antibiotics have similar efficacy, Dr. Youngster explained.

In addition to cost and efficacy, the differences in tolerability between these two drugs should be considered when deciding on long-term intravenous treatment for MSSA in the OPAT setting, he said. A failure to tolerate treatment will result in exposure to a partially treated infection should treatment be discontinued prematurely, or to the inconvenience of returning for another evaluation and a change of treatment.

Although the current study did not compare the efficacy of the two drugs, a clinical data collection system now in place will allow for such assessments going forward, he said.

IDWeek is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Youngster reported having no disclosures.

SAN FRANCISCO – Cefazolin was better tolerated than nafcillin for the outpatient treatment of methicillin-sensitive Staphylococcus aureus among clinic patients included in a retrospective cohort study.

A number of drug-related adverse events occurred more often in 366 patients who received outpatient parenteral antimicrobial therapy (OPAT) with nafcillin, compared with 119 patients treated with cefazolin, including rash (13.9% vs. 4.2%), renal dysfunction (11.4% vs. 3.3%), and transaminitis (8.1% vs. 1.6%), Dr. Ilan Youngster reported at an annual scientific meeting on infectious diseases.

The patients in this study were adults with a mean age of 57 years in the nafcillin group and 56 years in the cefazolin group.

Furthermore, neutropenia developed in 8.4% of nafcillin patients, compared with 3.3% of cefazolin patients, and Clostridium difficile colitis developed in 2.4% vs. 0.8% of the nafcillin and cefazolin patients, respectively, said Dr. Youngster, a research fellow at Boston Children’s Hospital and Massachusetts General Hospital, Boston.

The discontinuation rate was significantly higher in the nafcillin group than in the cefazolin group, with 34% and 7% of patients in the groups, respectively, failing to complete the prespecified treatment course, he said. Nine patients who discontinued nafcillin switched over to cefazolin and completed treatment without any further drug-related adverse events.

The findings have implications for treatment of methicillin-sensitive Staphylococcus aureus (MSSA), which is a major pathogen in both community and health care–acquired infection, and one of the most common infections requiring prolonged antimicrobial administration.

Both nafcillin and cefazolin are considered first-line options for therapy for most MSSA infections, and recent studies suggest that the two beta-lactam antibiotics have similar efficacy, Dr. Youngster explained.

In addition to cost and efficacy, the differences in tolerability between these two drugs should be considered when deciding on long-term intravenous treatment for MSSA in the OPAT setting, he said. A failure to tolerate treatment will result in exposure to a partially treated infection should treatment be discontinued prematurely, or to the inconvenience of returning for another evaluation and a change of treatment.

Although the current study did not compare the efficacy of the two drugs, a clinical data collection system now in place will allow for such assessments going forward, he said.

IDWeek is the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Dr. Youngster reported having no disclosures.