Kate Johnson

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence–which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924-31)

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707-14)

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, [and] sexual [and sleep] dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, treatment of most nonmotor PD symptoms should mirror the treatments given to non-PD patients,” she said.

However, the new guidelines provide evidence-based recommendations for the treatment of four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search aimed at capturing articles pertaining to these symptoms published between 1966 and 2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations. They also concluded that there was insufficient evidence to make recommendations regarding the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” They wrote, “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based one class II study.

The authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, though “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levo-dopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in PD.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study. However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz said.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Dr. Zesiewicz reported receiving funding for travel from and serving on speakers bureaus for Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence–which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924-31)

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707-14)

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, [and] sexual [and sleep] dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, treatment of most nonmotor PD symptoms should mirror the treatments given to non-PD patients,” she said.

However, the new guidelines provide evidence-based recommendations for the treatment of four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search aimed at capturing articles pertaining to these symptoms published between 1966 and 2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations. They also concluded that there was insufficient evidence to make recommendations regarding the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” They wrote, “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based one class II study.

The authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, though “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levo-dopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in PD.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study. However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz said.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Dr. Zesiewicz reported receiving funding for travel from and serving on speakers bureaus for Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence–which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924-31)

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707-14)

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, [and] sexual [and sleep] dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, treatment of most nonmotor PD symptoms should mirror the treatments given to non-PD patients,” she said.

However, the new guidelines provide evidence-based recommendations for the treatment of four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search aimed at capturing articles pertaining to these symptoms published between 1966 and 2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations. They also concluded that there was insufficient evidence to make recommendations regarding the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” They wrote, “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based one class II study.

The authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, though “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levo-dopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in PD.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study. However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz said.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Dr. Zesiewicz reported receiving funding for travel from and serving on speakers bureaus for Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Lip augmentation with autologous sternocleidomastoid muscle and fascia grafts results in enhanced vermilion show and lip projection up to 2 years post procedure, according to a single-center, retrospective study.

“This is another tool in the plastic surgeon’s armamentarium to combat the aging lip, which along with every other technique has some limitations, yet is effective in our practice,” wrote Dr. Anurag Agarwal, of the Aesthetic Surgery Center, Naples, Florida, and colleagues in the March/April issue of Archives of Facial Plastic Surgery.

“Based on the present study, patients who desire subtle, yet long-term lip augmentation can be counseled to expect approximately a 20% to 25% increase in vermilion show and approximately a 1-mm increase in lip projection at 2 years and longer from baseline.”

The study compared baseline and postprocedure photographs of 25 consecutive patients who underwent sternocleidomastoid (SCM) muscle and fascia augmentation of the lips with concurrent cervicofacial rhytidectomy (Arch. Facial Plast. Surg. 2010;12:97-102).

They were compared to similar baseline and postprocedure photographs of 25 control patients who received cervicofacial rhytidectomy alone, with no lip augmentation.

The mean postoperative photograph was taken at 25 months in the SCM group and 21 months in the control group. The ages of the patients were not reported.

For each patient, frontal and right lateral photographs were analyzed. The frontal analysis included measurement of the right and left, upper and lower lip vermilion show. The right lateral analysis included measurement of the anterior-most projection of the upper and lower lips.

Exclusion criteria included a concomitant chin augmentation, as well as use of injectable and/or surgical lip fillers or perioral skin resurfacing within 6 months of the preoperative photograph.

Compared with the group that did not receive lip augmentation, the mean changes from baseline in the lip augmentation group were statistically significant, reported the authors.

Comparing baseline and postprocedure photographs among the lip augmentation patients, the mean increase in upper lip projection from baseline was 0.99 mm, and in lower lip projection it was 0.90 mm. The mean increase in upper lip vermilion show from baseline was 20% on the right side and 22% on the left. The mean increase in lower lip vermilion show from baseline was 23% on the right side and 24% on the left.

Regarding complications, “there were no contour deformities, no limitations in head movement, no increased postauricular neck pain, no spinal accessory nerve injuries, and no difference in temporary numbness around the ears between the SCM graft and control group patients,” wrote the authors.

A medical chart review revealed that a deep focal lump developed in the upper lip of one SCM patient 3 years postoperatively. The etiology of the lump was unknown but it resolved after two triamcinolone acetonide injections, they reported.

“All patients were subjectively pleased with their degree of lip augmentation,” but one patient requested additional augmentation 2 years postoperatively, which was performed successfully with injectable gel, they said.

The SCM muscle and fascia graft has been performed by the authors since 1996, most commonly in conjunction with cervicofacial rhytidectomy, but also as a stand-alone procedure.

When performed with rhytidectomy, the superficial musculoaponeurotic system incision is extended inferiorly along the anterior border of the SCM muscle. Then, a segment of the SCM muscle and fascia is harvested from the mastoid process inferiorly, along the posterior border. Hemostasis is achieved with bipolar cautery, and the donor defect is closed.

After completion of the cervicofacial rhytidectomy, single incisions are made just inside the mucosa on each corner of the mouth, through which upper and lower lip tunnels are created in the superficial orbicularis oris muscle. The graft material is then pulled through the tunnels and positioned symmetrically, and the incisions are closed. “It is imperative to contour the grafts so that they are smooth and free of any muscle bulges that may be visible postoperatively,” they wrote. The grafts are intentionally left slightly longer than the distance between the incisions. “We have found that tucking the lateral ends of the grafts slightly lateral to the corner of the mouth incisions helps counteract the natural tendency for the grafts to horizontally shorten. This allows preservation of lateral lip fullness,” they explained.

After the procedure, antibiotic ointment is applied and patients are asked to limit their mouth opening for 2 weeks postoperatively.

When performed without rhytidectomy, “the same horizontal limb of the rhytidectomy incision is performed in the hair-bearing scalp to access this portion of the SCM, but the patient must be counseled about a donor site incision that would not be required with a nonautologous implant material.”

Neither dermal cysts, or prolonged stiffness or sensory changes were encountered in the study group – problems that have been reported with other lip augmentations procedures, they wrote.

“We have seen occasional asymmetries in the lips after SCM grafting,” they wrote. “Fortunately, these findings are rare,” they continued, without specifying their frequency in the study group. “There are several possible explanations for this finding: the presence of slight contour irregularities in the grafts when they are implanted; asymmetric graft compression; differential resorption with a given graft; and/or a contribution from dynamic movement of the lips.”

They study’s main limitation was some variation in the camera’s distance from the patient, although an attempt was made to control for this with the calibration of photographs, the authors wrote. In addition, they noted, patient satisfaction was not formally measured.

The researchers reported no financial disclosures.

Lip augmentation with autologous sternocleidomastoid muscle and fascia grafts results in enhanced vermilion show and lip projection up to 2 years post procedure, according to a single-center, retrospective study.

“This is another tool in the plastic surgeon’s armamentarium to combat the aging lip, which along with every other technique has some limitations, yet is effective in our practice,” wrote Dr. Anurag Agarwal, of the Aesthetic Surgery Center, Naples, Florida, and colleagues in the March/April issue of Archives of Facial Plastic Surgery.

“Based on the present study, patients who desire subtle, yet long-term lip augmentation can be counseled to expect approximately a 20% to 25% increase in vermilion show and approximately a 1-mm increase in lip projection at 2 years and longer from baseline.”

The study compared baseline and postprocedure photographs of 25 consecutive patients who underwent sternocleidomastoid (SCM) muscle and fascia augmentation of the lips with concurrent cervicofacial rhytidectomy (Arch. Facial Plast. Surg. 2010;12:97-102).

They were compared to similar baseline and postprocedure photographs of 25 control patients who received cervicofacial rhytidectomy alone, with no lip augmentation.

The mean postoperative photograph was taken at 25 months in the SCM group and 21 months in the control group. The ages of the patients were not reported.

For each patient, frontal and right lateral photographs were analyzed. The frontal analysis included measurement of the right and left, upper and lower lip vermilion show. The right lateral analysis included measurement of the anterior-most projection of the upper and lower lips.

Exclusion criteria included a concomitant chin augmentation, as well as use of injectable and/or surgical lip fillers or perioral skin resurfacing within 6 months of the preoperative photograph.

Compared with the group that did not receive lip augmentation, the mean changes from baseline in the lip augmentation group were statistically significant, reported the authors.

Comparing baseline and postprocedure photographs among the lip augmentation patients, the mean increase in upper lip projection from baseline was 0.99 mm, and in lower lip projection it was 0.90 mm. The mean increase in upper lip vermilion show from baseline was 20% on the right side and 22% on the left. The mean increase in lower lip vermilion show from baseline was 23% on the right side and 24% on the left.

Regarding complications, “there were no contour deformities, no limitations in head movement, no increased postauricular neck pain, no spinal accessory nerve injuries, and no difference in temporary numbness around the ears between the SCM graft and control group patients,” wrote the authors.

A medical chart review revealed that a deep focal lump developed in the upper lip of one SCM patient 3 years postoperatively. The etiology of the lump was unknown but it resolved after two triamcinolone acetonide injections, they reported.

“All patients were subjectively pleased with their degree of lip augmentation,” but one patient requested additional augmentation 2 years postoperatively, which was performed successfully with injectable gel, they said.

The SCM muscle and fascia graft has been performed by the authors since 1996, most commonly in conjunction with cervicofacial rhytidectomy, but also as a stand-alone procedure.

When performed with rhytidectomy, the superficial musculoaponeurotic system incision is extended inferiorly along the anterior border of the SCM muscle. Then, a segment of the SCM muscle and fascia is harvested from the mastoid process inferiorly, along the posterior border. Hemostasis is achieved with bipolar cautery, and the donor defect is closed.

After completion of the cervicofacial rhytidectomy, single incisions are made just inside the mucosa on each corner of the mouth, through which upper and lower lip tunnels are created in the superficial orbicularis oris muscle. The graft material is then pulled through the tunnels and positioned symmetrically, and the incisions are closed. “It is imperative to contour the grafts so that they are smooth and free of any muscle bulges that may be visible postoperatively,” they wrote. The grafts are intentionally left slightly longer than the distance between the incisions. “We have found that tucking the lateral ends of the grafts slightly lateral to the corner of the mouth incisions helps counteract the natural tendency for the grafts to horizontally shorten. This allows preservation of lateral lip fullness,” they explained.

After the procedure, antibiotic ointment is applied and patients are asked to limit their mouth opening for 2 weeks postoperatively.

When performed without rhytidectomy, “the same horizontal limb of the rhytidectomy incision is performed in the hair-bearing scalp to access this portion of the SCM, but the patient must be counseled about a donor site incision that would not be required with a nonautologous implant material.”

Neither dermal cysts, or prolonged stiffness or sensory changes were encountered in the study group – problems that have been reported with other lip augmentations procedures, they wrote.

“We have seen occasional asymmetries in the lips after SCM grafting,” they wrote. “Fortunately, these findings are rare,” they continued, without specifying their frequency in the study group. “There are several possible explanations for this finding: the presence of slight contour irregularities in the grafts when they are implanted; asymmetric graft compression; differential resorption with a given graft; and/or a contribution from dynamic movement of the lips.”

They study’s main limitation was some variation in the camera’s distance from the patient, although an attempt was made to control for this with the calibration of photographs, the authors wrote. In addition, they noted, patient satisfaction was not formally measured.

The researchers reported no financial disclosures.

Lip augmentation with autologous sternocleidomastoid muscle and fascia grafts results in enhanced vermilion show and lip projection up to 2 years post procedure, according to a single-center, retrospective study.

“This is another tool in the plastic surgeon’s armamentarium to combat the aging lip, which along with every other technique has some limitations, yet is effective in our practice,” wrote Dr. Anurag Agarwal, of the Aesthetic Surgery Center, Naples, Florida, and colleagues in the March/April issue of Archives of Facial Plastic Surgery.

“Based on the present study, patients who desire subtle, yet long-term lip augmentation can be counseled to expect approximately a 20% to 25% increase in vermilion show and approximately a 1-mm increase in lip projection at 2 years and longer from baseline.”

The study compared baseline and postprocedure photographs of 25 consecutive patients who underwent sternocleidomastoid (SCM) muscle and fascia augmentation of the lips with concurrent cervicofacial rhytidectomy (Arch. Facial Plast. Surg. 2010;12:97-102).

They were compared to similar baseline and postprocedure photographs of 25 control patients who received cervicofacial rhytidectomy alone, with no lip augmentation.

The mean postoperative photograph was taken at 25 months in the SCM group and 21 months in the control group. The ages of the patients were not reported.

For each patient, frontal and right lateral photographs were analyzed. The frontal analysis included measurement of the right and left, upper and lower lip vermilion show. The right lateral analysis included measurement of the anterior-most projection of the upper and lower lips.

Exclusion criteria included a concomitant chin augmentation, as well as use of injectable and/or surgical lip fillers or perioral skin resurfacing within 6 months of the preoperative photograph.

Compared with the group that did not receive lip augmentation, the mean changes from baseline in the lip augmentation group were statistically significant, reported the authors.

Comparing baseline and postprocedure photographs among the lip augmentation patients, the mean increase in upper lip projection from baseline was 0.99 mm, and in lower lip projection it was 0.90 mm. The mean increase in upper lip vermilion show from baseline was 20% on the right side and 22% on the left. The mean increase in lower lip vermilion show from baseline was 23% on the right side and 24% on the left.

Regarding complications, “there were no contour deformities, no limitations in head movement, no increased postauricular neck pain, no spinal accessory nerve injuries, and no difference in temporary numbness around the ears between the SCM graft and control group patients,” wrote the authors.

A medical chart review revealed that a deep focal lump developed in the upper lip of one SCM patient 3 years postoperatively. The etiology of the lump was unknown but it resolved after two triamcinolone acetonide injections, they reported.

“All patients were subjectively pleased with their degree of lip augmentation,” but one patient requested additional augmentation 2 years postoperatively, which was performed successfully with injectable gel, they said.

The SCM muscle and fascia graft has been performed by the authors since 1996, most commonly in conjunction with cervicofacial rhytidectomy, but also as a stand-alone procedure.

When performed with rhytidectomy, the superficial musculoaponeurotic system incision is extended inferiorly along the anterior border of the SCM muscle. Then, a segment of the SCM muscle and fascia is harvested from the mastoid process inferiorly, along the posterior border. Hemostasis is achieved with bipolar cautery, and the donor defect is closed.

After completion of the cervicofacial rhytidectomy, single incisions are made just inside the mucosa on each corner of the mouth, through which upper and lower lip tunnels are created in the superficial orbicularis oris muscle. The graft material is then pulled through the tunnels and positioned symmetrically, and the incisions are closed. “It is imperative to contour the grafts so that they are smooth and free of any muscle bulges that may be visible postoperatively,” they wrote. The grafts are intentionally left slightly longer than the distance between the incisions. “We have found that tucking the lateral ends of the grafts slightly lateral to the corner of the mouth incisions helps counteract the natural tendency for the grafts to horizontally shorten. This allows preservation of lateral lip fullness,” they explained.

After the procedure, antibiotic ointment is applied and patients are asked to limit their mouth opening for 2 weeks postoperatively.

When performed without rhytidectomy, “the same horizontal limb of the rhytidectomy incision is performed in the hair-bearing scalp to access this portion of the SCM, but the patient must be counseled about a donor site incision that would not be required with a nonautologous implant material.”

Neither dermal cysts, or prolonged stiffness or sensory changes were encountered in the study group – problems that have been reported with other lip augmentations procedures, they wrote.

“We have seen occasional asymmetries in the lips after SCM grafting,” they wrote. “Fortunately, these findings are rare,” they continued, without specifying their frequency in the study group. “There are several possible explanations for this finding: the presence of slight contour irregularities in the grafts when they are implanted; asymmetric graft compression; differential resorption with a given graft; and/or a contribution from dynamic movement of the lips.”

They study’s main limitation was some variation in the camera’s distance from the patient, although an attempt was made to control for this with the calibration of photographs, the authors wrote. In addition, they noted, patient satisfaction was not formally measured.

The researchers reported no financial disclosures.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” principal investigator Dr. Claire Bombardier said in an interview. The findings from this research show that physicians need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted that her study was limited by its reliance on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study included 14,214 patients with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (7,026 patients). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry.

Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence), comorbidity (based on the Charlson-Deyo comorbidity index), markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use), and RA-related drug exposure.

Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and 5.46 at a dose of 20 mg or more per day.

Other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, but less so, with ORs ranging from 1.1 to 3.64, Dr. Bombardier said.

Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” principal investigator Dr. Claire Bombardier said in an interview. The findings from this research show that physicians need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted that her study was limited by its reliance on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study included 14,214 patients with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (7,026 patients). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry.

Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence), comorbidity (based on the Charlson-Deyo comorbidity index), markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use), and RA-related drug exposure.

Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and 5.46 at a dose of 20 mg or more per day.

Other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, but less so, with ORs ranging from 1.1 to 3.64, Dr. Bombardier said.

Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” principal investigator Dr. Claire Bombardier said in an interview. The findings from this research show that physicians need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted that her study was limited by its reliance on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study included 14,214 patients with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (7,026 patients). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry.

Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence), comorbidity (based on the Charlson-Deyo comorbidity index), markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use), and RA-related drug exposure.

Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and 5.46 at a dose of 20 mg or more per day.

Other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, but less so, with ORs ranging from 1.1 to 3.64, Dr. Bombardier said.

Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

MONTREAL — Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a case-control study.

“All we're talking about here is an association. We can't infer causation,” the study's principal investigator, Dr. Dafna Gladman, said in an interview.

Previous, less-rigorous studies have suggested an association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto. “This study supports that notion—that environmental factors are important—but we think genetic factors are also involved,” as well as immunologic factors, she said.

At most, 30% of psoriasis patients go on to develop PsA, Dr. Gladman noted.

Her study, presented as a poster at the annual meeting of the Canadian Rheumatology Association, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone.

Men accounted for a similar percentage of both study groups (46% in the PsA group and 44% in the control group). The mean age of the participants in each group was similar (45 years and 48 years), as was the mean duration of psoriasis (17.5 years and 18.5 years). The mean duration of PsA was 3 years. All the patients with psoriasis were examined to ensure they didn't have psoriatic arthritis.

All of the patients completed a questionnaire to assess environmental factors during the past 10 years, including occupational trauma, infection, immunization, smoking, and psychological stress.

In a univariate analysis, a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an odds ratio of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8. The third-highest risk factor was any injury requiring medical attention (OR, 2.43).

In a multivariate logistic regression analysis, progression from psoriasis to PsA was significantly associated with severe infection requiring hospitalization (OR, 10.6), occupations requiring the lifting of heavy loads (OR, 2.7), and injuries requiring medical attention (excluding fractures and motor vehicle accidents) (OR, 2.3).

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” she said.

“And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress. In fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis,” Dr. Gladman commented.

In the multivariate analysis, smoking appeared to have a significant association with decreased risk, she added. Current smoking had an OR of 0.4 and past smoking had an OR of 0.5.

The findings are too preliminary to guide clinical practice at this time, Dr. Gladman said.

Still, psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it's the only factor, we don't know, because there are also genetic factors involved. It's quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

The next step should be to look at the possible role of genetic and environmental factors, she added.

Disclosures: Dr. Gladman declared no conflicts of interest.

MONTREAL — Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a case-control study.

“All we're talking about here is an association. We can't infer causation,” the study's principal investigator, Dr. Dafna Gladman, said in an interview.

Previous, less-rigorous studies have suggested an association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto. “This study supports that notion—that environmental factors are important—but we think genetic factors are also involved,” as well as immunologic factors, she said.

At most, 30% of psoriasis patients go on to develop PsA, Dr. Gladman noted.

Her study, presented as a poster at the annual meeting of the Canadian Rheumatology Association, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone.

Men accounted for a similar percentage of both study groups (46% in the PsA group and 44% in the control group). The mean age of the participants in each group was similar (45 years and 48 years), as was the mean duration of psoriasis (17.5 years and 18.5 years). The mean duration of PsA was 3 years. All the patients with psoriasis were examined to ensure they didn't have psoriatic arthritis.

All of the patients completed a questionnaire to assess environmental factors during the past 10 years, including occupational trauma, infection, immunization, smoking, and psychological stress.

In a univariate analysis, a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an odds ratio of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8. The third-highest risk factor was any injury requiring medical attention (OR, 2.43).

In a multivariate logistic regression analysis, progression from psoriasis to PsA was significantly associated with severe infection requiring hospitalization (OR, 10.6), occupations requiring the lifting of heavy loads (OR, 2.7), and injuries requiring medical attention (excluding fractures and motor vehicle accidents) (OR, 2.3).

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” she said.

“And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress. In fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis,” Dr. Gladman commented.

In the multivariate analysis, smoking appeared to have a significant association with decreased risk, she added. Current smoking had an OR of 0.4 and past smoking had an OR of 0.5.

The findings are too preliminary to guide clinical practice at this time, Dr. Gladman said.

Still, psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it's the only factor, we don't know, because there are also genetic factors involved. It's quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

The next step should be to look at the possible role of genetic and environmental factors, she added.

Disclosures: Dr. Gladman declared no conflicts of interest.

MONTREAL — Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a case-control study.

“All we're talking about here is an association. We can't infer causation,” the study's principal investigator, Dr. Dafna Gladman, said in an interview.

Previous, less-rigorous studies have suggested an association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto. “This study supports that notion—that environmental factors are important—but we think genetic factors are also involved,” as well as immunologic factors, she said.

At most, 30% of psoriasis patients go on to develop PsA, Dr. Gladman noted.

Her study, presented as a poster at the annual meeting of the Canadian Rheumatology Association, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone.

Men accounted for a similar percentage of both study groups (46% in the PsA group and 44% in the control group). The mean age of the participants in each group was similar (45 years and 48 years), as was the mean duration of psoriasis (17.5 years and 18.5 years). The mean duration of PsA was 3 years. All the patients with psoriasis were examined to ensure they didn't have psoriatic arthritis.

All of the patients completed a questionnaire to assess environmental factors during the past 10 years, including occupational trauma, infection, immunization, smoking, and psychological stress.

In a univariate analysis, a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an odds ratio of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8. The third-highest risk factor was any injury requiring medical attention (OR, 2.43).

In a multivariate logistic regression analysis, progression from psoriasis to PsA was significantly associated with severe infection requiring hospitalization (OR, 10.6), occupations requiring the lifting of heavy loads (OR, 2.7), and injuries requiring medical attention (excluding fractures and motor vehicle accidents) (OR, 2.3).

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” she said.

“And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress. In fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis,” Dr. Gladman commented.

In the multivariate analysis, smoking appeared to have a significant association with decreased risk, she added. Current smoking had an OR of 0.4 and past smoking had an OR of 0.5.

The findings are too preliminary to guide clinical practice at this time, Dr. Gladman said.

Still, psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it's the only factor, we don't know, because there are also genetic factors involved. It's quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

The next step should be to look at the possible role of genetic and environmental factors, she added.

Disclosures: Dr. Gladman declared no conflicts of interest.

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Montreal – Injury, heavy lifting, severe infection, or other forms of trauma were associated with the progression of psoriasis to psoriatic arthritis in a study presented at the annual meeting of the Canadian Rheumatology Association.

“All we're talking about here is an association; we can't infer causation,” said the study’s principal investigator, Dr. Dafna Gladman, in an interview.

Previous, less rigorous studies have suggested the association between trauma and psoriatic arthritis (PsA), said Dr. Gladman, professor of medicine at the University of Toronto and deputy director of the Centre for Prognosis Studies in the Rheumatic Diseases in that city.

“This study supports that notion – that environmental factors are important – but we think genetic factors are also involved,” as well as immunologic factors, she said, explaining that at most, 30% of psoriasis patients go on to develop PsA.

Her study, which was presented as a poster at the meeting, compared 159 patients who had PsA with the same number of control patients who had psoriasis alone, in order to identify risk factors for progression to PsA.

Men accounted for a similar percentage of both groups (46% in the PsA group and 44% in the controls). The mean age of participants in each group was similar (45 years and 48 years, respectively) as was the mean duration of psoriasis (17.5 years and 18.5 years, respectively). The mean duration of PsA was 3 years.

A questionnaire was administered to all patients to assess their environmental exposure over the past 10 years, including occupational trauma, infection, immunization, smoking status and history, and psychological stress.

Univariate and multivariate logistic regression analysis was used to determine the odds ratio of each exposure prior to the diagnosis of PsA.

“We actually examined all the patients with psoriasis to make sure they didn’t have psoriatic arthritis,” she said.

Univariate analysis revealed that a history of infection requiring hospitalization was the strongest risk factor for the development of PsA, with an OR of 11.7. (Infective diarrhea carried an OR of 2.11.)

The second-highest risk factor was in the category of occupational exposure. A history of work involving cumulative lifting of at least 100 lb/hr carried an OR of 2.9, and pushing cumulative loads of at least 200 lb/hr carried an OR of 1.8.

And the third-highest risk factor was any injury requiring medical attention (OR, 2.43).

Multivariate analysis revealed that injuries requiring medical attention but excluding fracture and motor vehicle accident (OR, 2.3; P = .03), occupations requiring the lifting of heavy loads (OR, 2.7; P = .002), and severe infection requiring hospitalization (OR, 10.6; P = .03) were significantly associated with progression from psoriasis to PsA.

“For exposure to immunizations we found no risk, but another group [of investigators] has found that immunization was higher in those who got arthritis,” said Dr. Gladman. “And psychological stress had no impact, although it has been reported that psoriatic patients without arthritis have a lot of stress; in fact, they may even have more because it turns out that patients with psoriasis and no arthritis actually have worse psoriasis.”

After the multifactorial analysis, smoking appeared to be associated with decreased risk, she added. Current smoking had an OR of 0.4 (P = .01), and past smoking had an OR of 0.5 (P = .04).

Dr. Gladman said that the findings are too preliminary to inform clinical recommendations at this time, but psoriasis patients should know that “if you have a job that requires a lot of lifting, you are more susceptible to getting psoriatic arthritis. Whether it’s the only factor, we don’t know, because there are also genetic factors involved. It’s quite possible that in those people who are genetically predisposed, if they also do this work, they are more likely to get arthritis.”

She said that the next step should be to look at genetic and environmental factors and see if they are independent or not.

Dr. Gladman declared no conflicts of interest.

Major Finding: Response rate to rituximab is highest in RA patients with elevated CRP and RF positivity.

Data Source: Post hoc analysis of data from REFLEX and SERENE trials.

Disclosures: The study was supported by Genentech Inc., F. Hoffmann-LaRoche Ltd., and Biogen Idec Inc. Dr. Faraawi reported receiving research grants from Roche, Pfizer Inc., UCB, Schering-Plough Corp., and Wyeth.

QUEBEC CITY — Baseline serologic biomarkers offer rheumatologists the possibility of tailoring rheumatoid arthritis medications to fit various subgroups of patients, thereby increasing the likelihood of achieving a good response to treatment, said Dr. Rafat Faraawi at the annual meeting of the Canadian Rheumatology Association.

In a sea of pharmaceuticals for RA, with no clear understanding of why some patients respond to one agent and not to another, biomarkers are a potential tool for predicting treatment response, Dr. Faraawi said in an interview with

“We still don't have guidelines on how to select pharmaceuticals. More or less, [the drugs] all have the same efficacy. There are minor differences, and then the selection depends on many factors.

“We depend on personal preference, physician experience, certain peculiarities of the drugs, mechanism of action,” according to Dr. Faraawi.

In a post hoc analysis of two large trials of rituximab, his group discovered that a subgroup of patients with high serum levels of C-reactive protein (CRP) as well as seropositivity for rheumatoid factor (RF) had the highest response to rituximab. “If you want to select patients who will get a response to this expensive biologic, then those with positive rheumatoid factor and an elevated C-reactive protein most likely will show a better response than [will] seronegative patients or those with low CRP.

“And if they have a combination of both, that is even better,” said Dr. Faraawi, who is a rheumatologist at McMaster University in Kitchener, Ont.

He presented the data as a poster at the meeting.

The investigators used data from REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) and SERENE (Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders).

Both are randomized, placebo-controlled trials of rituximab in patients with inadequate response to either tumor necrosis factor inhibitors or methotrexate, respectively (Arthritis Rheum. 2006;54:2793-806; ACR 2008, abstract 364).

Both trials reported ACR 50 response rates for rituximab, compared with placebo, after 24 weeks.

The REFLEX trial (n = 517) showed an ACR 50 response of 27% in the treated group, compared with 5% in placebo. And the SERENE trial (n = 501) showed an ACR 50 response of 26% in the treated group, compared with 9% in placebo.

For both trials, baseline levels of 19 serologic markers and 9 clinical features were recorded.

After an analysis of baseline and outcome data from both trials, Dr. Faraawi's study identified four serologic biomarkers—RF, CRP, IgG anti–cyclic citrullinated peptide 3 (CCP3) antibodies, and soluble cluster of differentiation 25 (CD25)—that were predictive of response to rituximab, he explained.

Of these, seropositivity for RF and CRP were the most predictive, and this was further enhanced when both biomarkers were presented.

For example, in the REFLEX trial, the overall ACR 50 response rate was 27% in the treated group, whereas the subgroup of patients with CRP levels above 2.9 mg/dL and positive RF of any isotope (defined as IgA RF greater than 25 U/mL, IgG RF greater than 20 U/mL, IgM RF greater than 20 U/mL, total RF greater than 20 IU/mL) had an ACR 50 response rate of 31% (placebo, 1%).

Similarly, in the SERENE trial, the overall ACR 50 response rate was 26% in the treated group, whereas the response rate was 39% in the same subgroup of patients who were positive for RF and had an elevated CRP (placebo, 7%).

Rituximab is a monoclonal antibody that selectively targets CD20-positive B cells, which secrete rheumatoid factor, said Dr. Faraawi.

“That is why, for this particular drug, patients with positive rheumatoid factor respond well. That doesn't mean this agent does not work for patients with low markers. It still works. But the likelihood of response is greater with positive markers.”

He said that large trials are needed to further clarify which markers can help in the selection of agents for specific patients.

Major Finding: Response rate to rituximab is highest in RA patients with elevated CRP and RF positivity.

Data Source: Post hoc analysis of data from REFLEX and SERENE trials.

Disclosures: The study was supported by Genentech Inc., F. Hoffmann-LaRoche Ltd., and Biogen Idec Inc. Dr. Faraawi reported receiving research grants from Roche, Pfizer Inc., UCB, Schering-Plough Corp., and Wyeth.

QUEBEC CITY — Baseline serologic biomarkers offer rheumatologists the possibility of tailoring rheumatoid arthritis medications to fit various subgroups of patients, thereby increasing the likelihood of achieving a good response to treatment, said Dr. Rafat Faraawi at the annual meeting of the Canadian Rheumatology Association.

In a sea of pharmaceuticals for RA, with no clear understanding of why some patients respond to one agent and not to another, biomarkers are a potential tool for predicting treatment response, Dr. Faraawi said in an interview with

“We still don't have guidelines on how to select pharmaceuticals. More or less, [the drugs] all have the same efficacy. There are minor differences, and then the selection depends on many factors.

“We depend on personal preference, physician experience, certain peculiarities of the drugs, mechanism of action,” according to Dr. Faraawi.

In a post hoc analysis of two large trials of rituximab, his group discovered that a subgroup of patients with high serum levels of C-reactive protein (CRP) as well as seropositivity for rheumatoid factor (RF) had the highest response to rituximab. “If you want to select patients who will get a response to this expensive biologic, then those with positive rheumatoid factor and an elevated C-reactive protein most likely will show a better response than [will] seronegative patients or those with low CRP.

“And if they have a combination of both, that is even better,” said Dr. Faraawi, who is a rheumatologist at McMaster University in Kitchener, Ont.

He presented the data as a poster at the meeting.

The investigators used data from REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) and SERENE (Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders).

Both are randomized, placebo-controlled trials of rituximab in patients with inadequate response to either tumor necrosis factor inhibitors or methotrexate, respectively (Arthritis Rheum. 2006;54:2793-806; ACR 2008, abstract 364).

Both trials reported ACR 50 response rates for rituximab, compared with placebo, after 24 weeks.

The REFLEX trial (n = 517) showed an ACR 50 response of 27% in the treated group, compared with 5% in placebo. And the SERENE trial (n = 501) showed an ACR 50 response of 26% in the treated group, compared with 9% in placebo.

For both trials, baseline levels of 19 serologic markers and 9 clinical features were recorded.

After an analysis of baseline and outcome data from both trials, Dr. Faraawi's study identified four serologic biomarkers—RF, CRP, IgG anti–cyclic citrullinated peptide 3 (CCP3) antibodies, and soluble cluster of differentiation 25 (CD25)—that were predictive of response to rituximab, he explained.

Of these, seropositivity for RF and CRP were the most predictive, and this was further enhanced when both biomarkers were presented.

For example, in the REFLEX trial, the overall ACR 50 response rate was 27% in the treated group, whereas the subgroup of patients with CRP levels above 2.9 mg/dL and positive RF of any isotope (defined as IgA RF greater than 25 U/mL, IgG RF greater than 20 U/mL, IgM RF greater than 20 U/mL, total RF greater than 20 IU/mL) had an ACR 50 response rate of 31% (placebo, 1%).

Similarly, in the SERENE trial, the overall ACR 50 response rate was 26% in the treated group, whereas the response rate was 39% in the same subgroup of patients who were positive for RF and had an elevated CRP (placebo, 7%).

Rituximab is a monoclonal antibody that selectively targets CD20-positive B cells, which secrete rheumatoid factor, said Dr. Faraawi.

“That is why, for this particular drug, patients with positive rheumatoid factor respond well. That doesn't mean this agent does not work for patients with low markers. It still works. But the likelihood of response is greater with positive markers.”

He said that large trials are needed to further clarify which markers can help in the selection of agents for specific patients.

Major Finding: Response rate to rituximab is highest in RA patients with elevated CRP and RF positivity.

Data Source: Post hoc analysis of data from REFLEX and SERENE trials.

Disclosures: The study was supported by Genentech Inc., F. Hoffmann-LaRoche Ltd., and Biogen Idec Inc. Dr. Faraawi reported receiving research grants from Roche, Pfizer Inc., UCB, Schering-Plough Corp., and Wyeth.

QUEBEC CITY — Baseline serologic biomarkers offer rheumatologists the possibility of tailoring rheumatoid arthritis medications to fit various subgroups of patients, thereby increasing the likelihood of achieving a good response to treatment, said Dr. Rafat Faraawi at the annual meeting of the Canadian Rheumatology Association.

In a sea of pharmaceuticals for RA, with no clear understanding of why some patients respond to one agent and not to another, biomarkers are a potential tool for predicting treatment response, Dr. Faraawi said in an interview with

“We still don't have guidelines on how to select pharmaceuticals. More or less, [the drugs] all have the same efficacy. There are minor differences, and then the selection depends on many factors.

“We depend on personal preference, physician experience, certain peculiarities of the drugs, mechanism of action,” according to Dr. Faraawi.

In a post hoc analysis of two large trials of rituximab, his group discovered that a subgroup of patients with high serum levels of C-reactive protein (CRP) as well as seropositivity for rheumatoid factor (RF) had the highest response to rituximab. “If you want to select patients who will get a response to this expensive biologic, then those with positive rheumatoid factor and an elevated C-reactive protein most likely will show a better response than [will] seronegative patients or those with low CRP.

“And if they have a combination of both, that is even better,” said Dr. Faraawi, who is a rheumatologist at McMaster University in Kitchener, Ont.

He presented the data as a poster at the meeting.

The investigators used data from REFLEX (Randomized Evaluation of Long-Term Efficacy of Rituximab in RA) and SERENE (Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders).

Both are randomized, placebo-controlled trials of rituximab in patients with inadequate response to either tumor necrosis factor inhibitors or methotrexate, respectively (Arthritis Rheum. 2006;54:2793-806; ACR 2008, abstract 364).

Both trials reported ACR 50 response rates for rituximab, compared with placebo, after 24 weeks.

The REFLEX trial (n = 517) showed an ACR 50 response of 27% in the treated group, compared with 5% in placebo. And the SERENE trial (n = 501) showed an ACR 50 response of 26% in the treated group, compared with 9% in placebo.

For both trials, baseline levels of 19 serologic markers and 9 clinical features were recorded.

After an analysis of baseline and outcome data from both trials, Dr. Faraawi's study identified four serologic biomarkers—RF, CRP, IgG anti–cyclic citrullinated peptide 3 (CCP3) antibodies, and soluble cluster of differentiation 25 (CD25)—that were predictive of response to rituximab, he explained.

Of these, seropositivity for RF and CRP were the most predictive, and this was further enhanced when both biomarkers were presented.

For example, in the REFLEX trial, the overall ACR 50 response rate was 27% in the treated group, whereas the subgroup of patients with CRP levels above 2.9 mg/dL and positive RF of any isotope (defined as IgA RF greater than 25 U/mL, IgG RF greater than 20 U/mL, IgM RF greater than 20 U/mL, total RF greater than 20 IU/mL) had an ACR 50 response rate of 31% (placebo, 1%).

Similarly, in the SERENE trial, the overall ACR 50 response rate was 26% in the treated group, whereas the response rate was 39% in the same subgroup of patients who were positive for RF and had an elevated CRP (placebo, 7%).

Rituximab is a monoclonal antibody that selectively targets CD20-positive B cells, which secrete rheumatoid factor, said Dr. Faraawi.

“That is why, for this particular drug, patients with positive rheumatoid factor respond well. That doesn't mean this agent does not work for patients with low markers. It still works. But the likelihood of response is greater with positive markers.”

He said that large trials are needed to further clarify which markers can help in the selection of agents for specific patients.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” said principal investigator Dr. Claire Bombardier in an interview. The findings from this research show that rheumatologists need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted her study's serious flaw: It relies on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study involved a total of 14,214 subjects with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (n = 7,026). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry. Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence); comorbidity (based on the Charlson-Deyo comorbidity index); markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use); and RA-related drug exposure. Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and the OR was 5.46 at a dose of 20 mg or more per day.

But other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, although less so, with ORs ranging from 1.1 to 3.64, said Dr. Bombardier. Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” said principal investigator Dr. Claire Bombardier in an interview. The findings from this research show that rheumatologists need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted her study's serious flaw: It relies on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study involved a total of 14,214 subjects with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (n = 7,026). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry. Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence); comorbidity (based on the Charlson-Deyo comorbidity index); markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use); and RA-related drug exposure. Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and the OR was 5.46 at a dose of 20 mg or more per day.

But other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, although less so, with ORs ranging from 1.1 to 3.64, said Dr. Bombardier. Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

QUEBEC CITY — The increased rate of serious infections seen in patients with rheumatoid arthritis is most strongly associated with current glucocorticoid exposure, but comorbidities are also an important factor, according to findings from a large, nested, case-control study presented at the annual meeting of the Canadian Rheumatology Association.

“When we try to predict risk of infection, we tend to focus on the drugs, particularly the immunosuppressive agents,” said principal investigator Dr. Claire Bombardier in an interview. The findings from this research show that rheumatologists need to pay more attention to other, heretofore largely overlooked risk factors, she added.

Dr. Bombardier noted her study's serious flaw: It relies on data from a source that does not include complete information on exposure to biologic agents. Use of biologics has been linked to an increased risk for reactivation of tuberculosis as well as primary fungal and other infections.

In two separate posters, Dr. Bombardier presented a retrospective examination of serious infections requiring hospitalization, as well as serious fungal infections, in a cohort of 81,497 seniors with RA.

All subjects were aged older than 65 years (mean, 69 years), and were drawn from the Ontario Biologics Research Initiative administrative database, said Dr. Bombardier, professor of medicine and director of the division of rheumatology at the University of Toronto.

The first study involved a total of 14,214 subjects with serious infection requiring hospitalization in 1992-2006, with the most common infection being pneumonia (n = 7,026). These subjects were matched to controls from the same cohort according to age, sex, and year of cohort entry. Multivariate logistic regression analysis was used to assess the independent effects of demographics (age, income, rural/urban residence); comorbidity (based on the Charlson-Deyo comorbidity index); markers of RA severity (number of rheumatology visits, history of joint replacement, presence of extra-articular RA, and prescription NSAID use); and RA-related drug exposure. Past and current drug exposures were determined based on electronic provincial prescription data, although most biologic use was probably not captured in this database because it is not covered by provincial health insurance.

After adjustment, the study found that current use of glucocorticoids was associated with the highest risk of infection, and that this risk increased with increasing doses. Compared with no exposure, a glucocorticoid dose of 5 mg or less per day was associated with an odds ratio of infection of 3.81. At 6-9 mg/day, the OR was 4.56, rising to 5.58 at a dose of 10-19 mg/day, and the OR was 5.46 at a dose of 20 mg or more per day.

But other drugs—both biologics (to the extent their effect was assessed) and disease-modifying antirheumatic drugs—were also associated with risk, although less so, with ORs ranging from 1.1 to 3.64, said Dr. Bombardier. Within the context of these nonglucocorticoid drugs, comorbidity and markers of disease severity were associated with a similar range of risks of infection. Chronic lung disease was associated with an OR of 1.47, and renal disease with OR of 1.38. The Charlson-Deyo comorbidity index score of 1 had an OR of 1.44, whereas a score of 2 or more had an OR of 1.59.

In terms of markers of disease activity, the presence of one or more extra-articular feature of RA was associated with an OR of 1.14, and a history of joint replacement with an OR of 1.05.

Dr. Bombardier's second study focused specifically on the risk of serious fungal infections within the same cohort, because of “the flurry of interest in fungal infections recently,” she said.

A total of 53 serious fungal infections occurred within the cohort, including aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and systemic candidiasis. As with the previous study, cases of infection were matched to 265 controls from the same cohort.

Again, univariate and multivariate logistic regression analysis assessed the independent effects of demographics, comorbidity, markers of RA severity, and RA-related drug exposure.

After adjustment, the study found that cases were more likely than controls to live in rural areas (OR, 6.8) and to have more comorbidity, most commonly lung (OR, 1.27) and renal disease (OR, 1.95).

Compared with no prednisone, there was a greater risk of fungal infection associated with prednisone doses of 10-19 mg/day (OR, 1.90) and more than 20 mg/day (OR, 4.0).

Only 17 of 53 cases were currently exposed to a DMARD at the time of the fungal infection, and no case was currently exposed to a biologic agent.

Compared with no exposure, a higher risk of infection was associated with current exposure to sulfasalazine (OR, 1.90), methotrexate (OR, 1.66), and hydroxychloroquine (OR, 1.64).

Dr. Bombardier said this information should help physicians refine decision making about adjusting RA patients' medication dose.

“When you're worrying about a patient, don't focus just on the drugs. Think about whether they have renal disease, or whether they have lung disease. That is as important [as], if not more important than, worrying about the drugs,” she said.

Disclosures: Funding for the study was provided by the Canadian Institute of Health Research and the Ontario Ministry of Health and Long-Term Care. Dr. Bombardier holds a Canada Research Chair in Knowledge Transfer for Musculoskeletal Care.

Major Finding: Hallucinations are a common finding in children with NPSLE.

Data Source: An observational study of 53 children with juvenile SLE with neuropsychiatric manifestations.

Disclosures: Dr. Lim reported no financial conflicts of interest.

MONTREAL — Pediatric neuropsychiatric systemic lupus erythematosus has several unique manifestations that are not seen in adult patients, and without precise questioning they could easily be missed, reported Dr. Lily Siok Hoon Lim.

Patients can have visual, auditory, and even tactile hallucinations, but about 70% of them have “preservation of insight,” meaning they know these experiences are not real, said Dr. Lim, a rheumatologist at the Hospital for Sick Children in Toronto. Because they can distinguish between hallucinations and reality, the children repress their symptoms and do not tell their parents or physicians “because they don't want to be seen as crazy,” she said in an interview.

Visual hallucination and distortion are seen in three-quarters of pediatric patients with neuropsychiatric systemic lupus erythematosus (NPSLE) but have not been documented in adults with NPSLE, Dr. Lim said at the annual meeting of the Canadian Rheumatology Association. “They may be looking at a picture frame on the wall, and it might distort and move in and out at them. We find a lot of patients have had mild symptoms for a long time without reporting them. Also a lot of them see bugs, or spiders crawling towards them, and that is very frightening,” she said.

In an observational study which she presented as a poster at the meeting, Dr. Lim and her colleagues followed a cohort of children with NPSLE at a single center between August 1985 and December 2008. Of a total of 447 children with juvenile SLE, 53 (12%) children and adolescents (46 female) exhibited secondary psychiatric manifestations and cognitive dysfunction. Half of the subjects had psychiatric manifestations at first presentation of JSLE and 77% exhibited them within a year of diagnosis. The median age of diagnosis with psychiatric illness was 15.9 years and the median duration of psychiatric symptoms prior to diagnosis was 60 days.

Clinical and laboratory measures, imaging features, and treatment regimens were collected using standardized assessment forms, and all patients were evaluated by an experienced psychiatrist.

The clinical features of lupus-related psychiatric disease were identified and classified according to American College of Rheumatology nomenclature for adult disease (Arthritis Rheum. 1999;42:599-608), with the exception of cognitive dysfunction. “Cognitive dysfunction is controversial in lupus because if you take a whole population of lupus patients and systematically study them with neurocognitive tests, 60% of them will have something, but it's subclinical; it doesn't affect how they function,” said Dr. Lim.

For this study, the investigators developed a definition of pediatric cognitive dysfunction that included patient- or parent-reported memory or attention deficit affecting academic performance. Specifically, a patient needed to fulfill the following three criteria: self-reported or observed problems with concentration or memory; significant impairment of the patient's academic performance, as indicated by a significant drop in grades; and improvement following treatment.

Using this definition, the study revealed that all patients had significant cognitive dysfunction, said Dr. Lim. “What's special is that our patients had actually reported these problems. For example, their short-term memory was bad; they couldn't remember what they ate for breakfast, or what their homework was. They also couldn't learn new stuff at school, they had word-finding difficulties, and they were also not doing well in school. So you may have had an A student going down to C.”

She said that 85% of the subjects had concentration difficulties, 77% had memory deficits, 23% had psychomotor slowing, and 21% had decreased comprehension. Two patients also had prominent depressive features.

In addition, 75% of the subjects also had psychosis with hallucinations. In 83% the hallucinations were auditory, 75% were visual, and 20% were tactile. Visual distortion also was reported in 38% of this psychosis subset, she said.

In all, 42 of the 53 patients underwent magnetic resonance brain imaging, of whom 45% had normal results, 29% had cerebral atrophy only, and 17% had nonspecific white matter changes only. Of the 53 patients, 28 underwent lumbar puncture, of whom 64% had normal results, 29% had elevated total protein, and 7% had an elevated white cell count.

Prednisone was started in all patients and increased according to standard protocol. In addition, all but three patients required second-line immunosuppressant therapy (85% with azathioprine, 55% with cyclophosphamide, and 28% with mycophenolate).

“What we're finding is that even among second-line immunosuppressants, cyclophosphamide is turning out to be something that is very useful,” commented Dr. Lim. “When we start patients on azathioprine because their symptoms are mainly cognitive, or they have only mild psychotic symptoms, we find that a third actually need to be switched over.” Of the patients with psychosis, 60% (n = 24) also required antipsychotic therapy.

The investigators were able to collect data on response to therapy for some of the patients: Six relapsed and 25 went on to remission (although 3 of these eventually relapsed).

Response was defined as the absence of psychiatric symptoms, no antipsychotic medication, and prednisone at less than 50% of the peak dose for at least 3 months. Remission was defined as absence of psychiatric symptoms, no antipsychotic medication, prednisone at 10 mg or less a day, or 0.2 mg/kg per day or less for at least 3 months. And relapse was defined as a recurrence of psychiatric symptoms, a requirement of at least a 50% increase in prednisone dose, or a change in second-line immunosuppressive agents (not due to adverse effects), or the addition of antipsychotic medication. There were 14 nonresponders. “The nonresponse may be because they presented in adolescence, and the follow-up was short before they transferred to an adult clinic,” she said.

Major Finding: Hallucinations are a common finding in children with NPSLE.

Data Source: An observational study of 53 children with juvenile SLE with neuropsychiatric manifestations.

Disclosures: Dr. Lim reported no financial conflicts of interest.

MONTREAL — Pediatric neuropsychiatric systemic lupus erythematosus has several unique manifestations that are not seen in adult patients, and without precise questioning they could easily be missed, reported Dr. Lily Siok Hoon Lim.

Patients can have visual, auditory, and even tactile hallucinations, but about 70% of them have “preservation of insight,” meaning they know these experiences are not real, said Dr. Lim, a rheumatologist at the Hospital for Sick Children in Toronto. Because they can distinguish between hallucinations and reality, the children repress their symptoms and do not tell their parents or physicians “because they don't want to be seen as crazy,” she said in an interview.

Visual hallucination and distortion are seen in three-quarters of pediatric patients with neuropsychiatric systemic lupus erythematosus (NPSLE) but have not been documented in adults with NPSLE, Dr. Lim said at the annual meeting of the Canadian Rheumatology Association. “They may be looking at a picture frame on the wall, and it might distort and move in and out at them. We find a lot of patients have had mild symptoms for a long time without reporting them. Also a lot of them see bugs, or spiders crawling towards them, and that is very frightening,” she said.

In an observational study which she presented as a poster at the meeting, Dr. Lim and her colleagues followed a cohort of children with NPSLE at a single center between August 1985 and December 2008. Of a total of 447 children with juvenile SLE, 53 (12%) children and adolescents (46 female) exhibited secondary psychiatric manifestations and cognitive dysfunction. Half of the subjects had psychiatric manifestations at first presentation of JSLE and 77% exhibited them within a year of diagnosis. The median age of diagnosis with psychiatric illness was 15.9 years and the median duration of psychiatric symptoms prior to diagnosis was 60 days.

Clinical and laboratory measures, imaging features, and treatment regimens were collected using standardized assessment forms, and all patients were evaluated by an experienced psychiatrist.

The clinical features of lupus-related psychiatric disease were identified and classified according to American College of Rheumatology nomenclature for adult disease (Arthritis Rheum. 1999;42:599-608), with the exception of cognitive dysfunction. “Cognitive dysfunction is controversial in lupus because if you take a whole population of lupus patients and systematically study them with neurocognitive tests, 60% of them will have something, but it's subclinical; it doesn't affect how they function,” said Dr. Lim.

For this study, the investigators developed a definition of pediatric cognitive dysfunction that included patient- or parent-reported memory or attention deficit affecting academic performance. Specifically, a patient needed to fulfill the following three criteria: self-reported or observed problems with concentration or memory; significant impairment of the patient's academic performance, as indicated by a significant drop in grades; and improvement following treatment.

Using this definition, the study revealed that all patients had significant cognitive dysfunction, said Dr. Lim. “What's special is that our patients had actually reported these problems. For example, their short-term memory was bad; they couldn't remember what they ate for breakfast, or what their homework was. They also couldn't learn new stuff at school, they had word-finding difficulties, and they were also not doing well in school. So you may have had an A student going down to C.”

She said that 85% of the subjects had concentration difficulties, 77% had memory deficits, 23% had psychomotor slowing, and 21% had decreased comprehension. Two patients also had prominent depressive features.

In addition, 75% of the subjects also had psychosis with hallucinations. In 83% the hallucinations were auditory, 75% were visual, and 20% were tactile. Visual distortion also was reported in 38% of this psychosis subset, she said.

In all, 42 of the 53 patients underwent magnetic resonance brain imaging, of whom 45% had normal results, 29% had cerebral atrophy only, and 17% had nonspecific white matter changes only. Of the 53 patients, 28 underwent lumbar puncture, of whom 64% had normal results, 29% had elevated total protein, and 7% had an elevated white cell count.

Prednisone was started in all patients and increased according to standard protocol. In addition, all but three patients required second-line immunosuppressant therapy (85% with azathioprine, 55% with cyclophosphamide, and 28% with mycophenolate).

“What we're finding is that even among second-line immunosuppressants, cyclophosphamide is turning out to be something that is very useful,” commented Dr. Lim. “When we start patients on azathioprine because their symptoms are mainly cognitive, or they have only mild psychotic symptoms, we find that a third actually need to be switched over.” Of the patients with psychosis, 60% (n = 24) also required antipsychotic therapy.

The investigators were able to collect data on response to therapy for some of the patients: Six relapsed and 25 went on to remission (although 3 of these eventually relapsed).

Response was defined as the absence of psychiatric symptoms, no antipsychotic medication, and prednisone at less than 50% of the peak dose for at least 3 months. Remission was defined as absence of psychiatric symptoms, no antipsychotic medication, prednisone at 10 mg or less a day, or 0.2 mg/kg per day or less for at least 3 months. And relapse was defined as a recurrence of psychiatric symptoms, a requirement of at least a 50% increase in prednisone dose, or a change in second-line immunosuppressive agents (not due to adverse effects), or the addition of antipsychotic medication. There were 14 nonresponders. “The nonresponse may be because they presented in adolescence, and the follow-up was short before they transferred to an adult clinic,” she said.

Major Finding: Hallucinations are a common finding in children with NPSLE.

Data Source: An observational study of 53 children with juvenile SLE with neuropsychiatric manifestations.

Disclosures: Dr. Lim reported no financial conflicts of interest.

MONTREAL — Pediatric neuropsychiatric systemic lupus erythematosus has several unique manifestations that are not seen in adult patients, and without precise questioning they could easily be missed, reported Dr. Lily Siok Hoon Lim.

Patients can have visual, auditory, and even tactile hallucinations, but about 70% of them have “preservation of insight,” meaning they know these experiences are not real, said Dr. Lim, a rheumatologist at the Hospital for Sick Children in Toronto. Because they can distinguish between hallucinations and reality, the children repress their symptoms and do not tell their parents or physicians “because they don't want to be seen as crazy,” she said in an interview.

Visual hallucination and distortion are seen in three-quarters of pediatric patients with neuropsychiatric systemic lupus erythematosus (NPSLE) but have not been documented in adults with NPSLE, Dr. Lim said at the annual meeting of the Canadian Rheumatology Association. “They may be looking at a picture frame on the wall, and it might distort and move in and out at them. We find a lot of patients have had mild symptoms for a long time without reporting them. Also a lot of them see bugs, or spiders crawling towards them, and that is very frightening,” she said.

In an observational study which she presented as a poster at the meeting, Dr. Lim and her colleagues followed a cohort of children with NPSLE at a single center between August 1985 and December 2008. Of a total of 447 children with juvenile SLE, 53 (12%) children and adolescents (46 female) exhibited secondary psychiatric manifestations and cognitive dysfunction. Half of the subjects had psychiatric manifestations at first presentation of JSLE and 77% exhibited them within a year of diagnosis. The median age of diagnosis with psychiatric illness was 15.9 years and the median duration of psychiatric symptoms prior to diagnosis was 60 days.

Clinical and laboratory measures, imaging features, and treatment regimens were collected using standardized assessment forms, and all patients were evaluated by an experienced psychiatrist.

The clinical features of lupus-related psychiatric disease were identified and classified according to American College of Rheumatology nomenclature for adult disease (Arthritis Rheum. 1999;42:599-608), with the exception of cognitive dysfunction. “Cognitive dysfunction is controversial in lupus because if you take a whole population of lupus patients and systematically study them with neurocognitive tests, 60% of them will have something, but it's subclinical; it doesn't affect how they function,” said Dr. Lim.

For this study, the investigators developed a definition of pediatric cognitive dysfunction that included patient- or parent-reported memory or attention deficit affecting academic performance. Specifically, a patient needed to fulfill the following three criteria: self-reported or observed problems with concentration or memory; significant impairment of the patient's academic performance, as indicated by a significant drop in grades; and improvement following treatment.

Using this definition, the study revealed that all patients had significant cognitive dysfunction, said Dr. Lim. “What's special is that our patients had actually reported these problems. For example, their short-term memory was bad; they couldn't remember what they ate for breakfast, or what their homework was. They also couldn't learn new stuff at school, they had word-finding difficulties, and they were also not doing well in school. So you may have had an A student going down to C.”

She said that 85% of the subjects had concentration difficulties, 77% had memory deficits, 23% had psychomotor slowing, and 21% had decreased comprehension. Two patients also had prominent depressive features.

In addition, 75% of the subjects also had psychosis with hallucinations. In 83% the hallucinations were auditory, 75% were visual, and 20% were tactile. Visual distortion also was reported in 38% of this psychosis subset, she said.

In all, 42 of the 53 patients underwent magnetic resonance brain imaging, of whom 45% had normal results, 29% had cerebral atrophy only, and 17% had nonspecific white matter changes only. Of the 53 patients, 28 underwent lumbar puncture, of whom 64% had normal results, 29% had elevated total protein, and 7% had an elevated white cell count.

Prednisone was started in all patients and increased according to standard protocol. In addition, all but three patients required second-line immunosuppressant therapy (85% with azathioprine, 55% with cyclophosphamide, and 28% with mycophenolate).

“What we're finding is that even among second-line immunosuppressants, cyclophosphamide is turning out to be something that is very useful,” commented Dr. Lim. “When we start patients on azathioprine because their symptoms are mainly cognitive, or they have only mild psychotic symptoms, we find that a third actually need to be switched over.” Of the patients with psychosis, 60% (n = 24) also required antipsychotic therapy.

The investigators were able to collect data on response to therapy for some of the patients: Six relapsed and 25 went on to remission (although 3 of these eventually relapsed).

Response was defined as the absence of psychiatric symptoms, no antipsychotic medication, and prednisone at less than 50% of the peak dose for at least 3 months. Remission was defined as absence of psychiatric symptoms, no antipsychotic medication, prednisone at 10 mg or less a day, or 0.2 mg/kg per day or less for at least 3 months. And relapse was defined as a recurrence of psychiatric symptoms, a requirement of at least a 50% increase in prednisone dose, or a change in second-line immunosuppressive agents (not due to adverse effects), or the addition of antipsychotic medication. There were 14 nonresponders. “The nonresponse may be because they presented in adolescence, and the follow-up was short before they transferred to an adult clinic,” she said.

Montreal — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over a 10-year period, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and decade of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years after the start of the study, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

Both disease and treatment can result in lupus-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“The SDI differentiates between damage which is definitely corticosteroid related (specifically ocular and musculoskeletal damage) vs. possibly corticosteroid related (such as cardiovascular, peripheral vascular, neuropsychiatric, and diabetic damage) vs. damage that occurs independent of corticosteroid use (specifically renal, pulmonary, dermatologic, and gonadal damage), as well as malignancy,” she said.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.” This subset of patients has less progressive disease-related damage, she added. Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. Approximately 60% of them flare and require treatment after a median of 3 years.

Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients.

“Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

Montreal — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over a 10-year period, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and decade of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years after the start of the study, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

Both disease and treatment can result in lupus-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“The SDI differentiates between damage which is definitely corticosteroid related (specifically ocular and musculoskeletal damage) vs. possibly corticosteroid related (such as cardiovascular, peripheral vascular, neuropsychiatric, and diabetic damage) vs. damage that occurs independent of corticosteroid use (specifically renal, pulmonary, dermatologic, and gonadal damage), as well as malignancy,” she said.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.” This subset of patients has less progressive disease-related damage, she added. Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. Approximately 60% of them flare and require treatment after a median of 3 years.

Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients.

“Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

Montreal — Patients with systemic lupus erythematosus that is serologically active but clinically quiescent do not require treatment with steroids or immunosuppressive agents until the disease flares, according to a study presented at the annual meeting of the Canadian Rheumatology Association.

Until now, patients with such discordant findings have presented a clinical dilemma, said Dr. Amanda Steiman, who presented the study's findings.

“Many physicians have wondered whether or not treatment is warranted in light of just the serological activity in the absence of any clinical disease,” she said in an interview. “Does lupus progress subclinically during a quiescent period?”

Her study followed 55 patients with serologically active, clinically quiescent (SACQ) systemic lupus erythematosus over a 10-year period, and compared their outcomes to those of 110 controls with classic SLE who were matched for age, sex, disease duration, and decade of clinic entry.

Patients and controls were also matched for baseline damage according to the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), incidence of renal damage, and incidence of coronary artery disease.

SACQ was defined as a minimum of 2 years without clinical activity and persistent serologic activity as defined by elevated anti–double stranded DNA and/or hypocomplementemia. Antimalarials were permissible during an SACQ period, but steroids or immunosuppressives were not.

The study found that, compared with controls, SACQ patients showed very little subclinical progression. At 3 years after the start of the study, SDI damage in the SACQ patients was 0.7 vs. 1.13 in controls; this pattern persisted at 5 years (0.89 vs. 1.36), 7 years (0.94 vs. 1.71), and 10 years (1.26 vs. 2.26).

Similarly, whereas 3.6% of the SACQ patients vs. 6.4% of controls had coronary artery disease at baseline, new cases of CAD (myocardial infarction, angina, or sudden cardiac death) occurred in 1.8% of SACQ patients vs. 7.3% of controls over the 10-year study.

One (1.8%) SACQ patient vs. 15.5% of controls had renal damage at 5 years, and at 10 years these numbers rose to 3.6% of SACQ patients and 23.6% of controls.

Both disease and treatment can result in lupus-related damage, said Dr. Steiman, who is a rheumatology fellow at the University of Toronto.

“The SDI differentiates between damage which is definitely corticosteroid related (specifically ocular and musculoskeletal damage) vs. possibly corticosteroid related (such as cardiovascular, peripheral vascular, neuropsychiatric, and diabetic damage) vs. damage that occurs independent of corticosteroid use (specifically renal, pulmonary, dermatologic, and gonadal damage), as well as malignancy,” she said.

“Especially later in the course of lupus—these patients were 11 years plus into their lupus course—a lot of the damage is related to treatment morbidity,” she said in an interview. “If we can avoid that for a good number of years, then we are going to spare the people the morbidity associated with the treatment.” This subset of patients has less progressive disease-related damage, she added. Findings from a previous study by Dr. Steiman's associates showed that patients with SACQ represent about 6% of the SLE population. Approximately 60% of them flare and require treatment after a median of 3 years.

Findings from the present study show that SACQ patients used antimalarials, corticosteroids, and immunosuppressives at rates of 60%, 18%, and 5%, respectively, during the study period, compared with 77%, 76%, and 44% in controls.

“The SACQ period can be a very prolonged period without a flare, and at our center we have not been treating these patients.

“Our study supports the practice of active surveillance without treatment, so that's reassuring.”

Disclosures: Dr. Steiman stated that she had no conflicts to disclose.

Major Finding: The SRI-50 tool signaled 50% improvement in 13 of the 24 SLEDAI-2K descriptors and in six of the nine assessed organ systems, findings that were undetected by the less-sensitive SLEDAI-2K.

Data Source: Results of SRI-50 in 100 patients.

Disclosures: Dr. Touma said he had no relevant financial conflicts to disclose.

MONTREAL — A proposed new tool that is sensitive enough to measure partial improvement in systemic lupus erythematosus could open the door to more precise monitoring of therapeutic response in both research and clinical practice, reported Dr. Zahi Touma at the annual meeting of the Canadian Rheumatology Association.

Currently, improvement in disease activity, or response to treatment, can be measured only as absent or present, using the SLEDAI-2K (Systemic Lupus Erythematosus Activity Index–2K), explained Dr. Touma, a clinical research fellow in rheumatology at the center for prognosis studies in the rheumatic diseases at the University of Toronto. However, this index is not designed to detect small but clinically meaningful improvements, he noted.

So his group developed a modified version, the SRI-50 (SLEDAI-2K Responder Index–50), which has been designed to capture at least a 50% response on the SLEDAI-2K. “We aimed to show a 50% improvement, because this was felt by clinicians to reflect a significant improvement,” he said in an interview.

The SRI-50 covers the same nine organ systems and uses the same 24 descriptors as does the SLEDAI-2K, said Dr. Touma. Scoring for each descriptor of SLEDAI-2K is halved to generate a new weighted score for each descriptor of the SRI-50.

For example, in a case of lupus nephritis that involves proteinuria at a level of serum protein in urine of 4 g/day, the SLEDAI-2K score would be 4.

At follow-up, a decrease in proteinuria to 2 g/day would generate the same SLEDAI-2K score of 4 (which is generated by any proteinuria above 0.5 g/day), but on the SRI-50, it would represent a 50% improvement and thus a score of 2.

To test the new measure, Dr. Touma's group performed a cross-sectional study of 100 patients who had experienced lupus flares or had persistently active disease.

The SLEDAI-2K was administered at the initial visit and then again after 1-3 months of treatment with prednisone and an immunosuppressant (hydroxychloroquine, azathioprine, methotrexate, or mycophenolate mofetil). The SRI-50 was also administered at the second visit.

Scores were calculated using a data retrieval form, with a range of scores from 1 (best) to 10 (worst) for each of the 24 descriptors. “It's very important to have a data retrieval form because if you are dealing with rash or arthritis you need a very accurate, standardized method of documentation,” he said.

For 72 patients, the SLEDAI-2K provided a satisfactory assessment at the second visit because their disease had either resolved completely or remained unchanged. However, for the remaining 28 patients, the SRI-50 signaled partial improvement that was undetected by the less-sensitive SLEDAI-2K. Among these patients, a 50% improvement was detected in 13 of the 24 descriptors and in six of the nine organ systems, said Dr. Touma.

Among these 28 patients, 90% were female, 53% were white, 16% were black, 10% were Chinese, and 21% were “other.” Their mean age at diagnosis was 32 years, and their mean duration of disease at first study visit was 13 years. Varying levels of disease activity were recorded at the first visit.

Three subjects had a SLEDAI-2K score of 2; three had a score of 4; six had a score of 6; six had a score of 8; three had a score of 10; two had a score of 12; one had a score of 16; one had a score of 18; two had a score of 20; and one had a score of 21.

Dr. Touma said the goal of the study was primarily to develop a more sensitive tool to measure outcomes in clinical trials. However, he believes the SRI-50 will also play an important role in clinical practice, where “it is always crucial to be able to show that a patient is responding to medical treatment.”

Major Finding: The SRI-50 tool signaled 50% improvement in 13 of the 24 SLEDAI-2K descriptors and in six of the nine assessed organ systems, findings that were undetected by the less-sensitive SLEDAI-2K.

Data Source: Results of SRI-50 in 100 patients.

Disclosures: Dr. Touma said he had no relevant financial conflicts to disclose.

MONTREAL — A proposed new tool that is sensitive enough to measure partial improvement in systemic lupus erythematosus could open the door to more precise monitoring of therapeutic response in both research and clinical practice, reported Dr. Zahi Touma at the annual meeting of the Canadian Rheumatology Association.

Currently, improvement in disease activity, or response to treatment, can be measured only as absent or present, using the SLEDAI-2K (Systemic Lupus Erythematosus Activity Index–2K), explained Dr. Touma, a clinical research fellow in rheumatology at the center for prognosis studies in the rheumatic diseases at the University of Toronto. However, this index is not designed to detect small but clinically meaningful improvements, he noted.

So his group developed a modified version, the SRI-50 (SLEDAI-2K Responder Index–50), which has been designed to capture at least a 50% response on the SLEDAI-2K. “We aimed to show a 50% improvement, because this was felt by clinicians to reflect a significant improvement,” he said in an interview.

The SRI-50 covers the same nine organ systems and uses the same 24 descriptors as does the SLEDAI-2K, said Dr. Touma. Scoring for each descriptor of SLEDAI-2K is halved to generate a new weighted score for each descriptor of the SRI-50.

For example, in a case of lupus nephritis that involves proteinuria at a level of serum protein in urine of 4 g/day, the SLEDAI-2K score would be 4.

At follow-up, a decrease in proteinuria to 2 g/day would generate the same SLEDAI-2K score of 4 (which is generated by any proteinuria above 0.5 g/day), but on the SRI-50, it would represent a 50% improvement and thus a score of 2.

To test the new measure, Dr. Touma's group performed a cross-sectional study of 100 patients who had experienced lupus flares or had persistently active disease.

The SLEDAI-2K was administered at the initial visit and then again after 1-3 months of treatment with prednisone and an immunosuppressant (hydroxychloroquine, azathioprine, methotrexate, or mycophenolate mofetil). The SRI-50 was also administered at the second visit.

Scores were calculated using a data retrieval form, with a range of scores from 1 (best) to 10 (worst) for each of the 24 descriptors. “It's very important to have a data retrieval form because if you are dealing with rash or arthritis you need a very accurate, standardized method of documentation,” he said.

For 72 patients, the SLEDAI-2K provided a satisfactory assessment at the second visit because their disease had either resolved completely or remained unchanged. However, for the remaining 28 patients, the SRI-50 signaled partial improvement that was undetected by the less-sensitive SLEDAI-2K. Among these patients, a 50% improvement was detected in 13 of the 24 descriptors and in six of the nine organ systems, said Dr. Touma.

Among these 28 patients, 90% were female, 53% were white, 16% were black, 10% were Chinese, and 21% were “other.” Their mean age at diagnosis was 32 years, and their mean duration of disease at first study visit was 13 years. Varying levels of disease activity were recorded at the first visit.

Three subjects had a SLEDAI-2K score of 2; three had a score of 4; six had a score of 6; six had a score of 8; three had a score of 10; two had a score of 12; one had a score of 16; one had a score of 18; two had a score of 20; and one had a score of 21.

Dr. Touma said the goal of the study was primarily to develop a more sensitive tool to measure outcomes in clinical trials. However, he believes the SRI-50 will also play an important role in clinical practice, where “it is always crucial to be able to show that a patient is responding to medical treatment.”

Major Finding: The SRI-50 tool signaled 50% improvement in 13 of the 24 SLEDAI-2K descriptors and in six of the nine assessed organ systems, findings that were undetected by the less-sensitive SLEDAI-2K.

Data Source: Results of SRI-50 in 100 patients.

Disclosures: Dr. Touma said he had no relevant financial conflicts to disclose.

MONTREAL — A proposed new tool that is sensitive enough to measure partial improvement in systemic lupus erythematosus could open the door to more precise monitoring of therapeutic response in both research and clinical practice, reported Dr. Zahi Touma at the annual meeting of the Canadian Rheumatology Association.

Currently, improvement in disease activity, or response to treatment, can be measured only as absent or present, using the SLEDAI-2K (Systemic Lupus Erythematosus Activity Index–2K), explained Dr. Touma, a clinical research fellow in rheumatology at the center for prognosis studies in the rheumatic diseases at the University of Toronto. However, this index is not designed to detect small but clinically meaningful improvements, he noted.

So his group developed a modified version, the SRI-50 (SLEDAI-2K Responder Index–50), which has been designed to capture at least a 50% response on the SLEDAI-2K. “We aimed to show a 50% improvement, because this was felt by clinicians to reflect a significant improvement,” he said in an interview.

The SRI-50 covers the same nine organ systems and uses the same 24 descriptors as does the SLEDAI-2K, said Dr. Touma. Scoring for each descriptor of SLEDAI-2K is halved to generate a new weighted score for each descriptor of the SRI-50.

For example, in a case of lupus nephritis that involves proteinuria at a level of serum protein in urine of 4 g/day, the SLEDAI-2K score would be 4.

At follow-up, a decrease in proteinuria to 2 g/day would generate the same SLEDAI-2K score of 4 (which is generated by any proteinuria above 0.5 g/day), but on the SRI-50, it would represent a 50% improvement and thus a score of 2.

To test the new measure, Dr. Touma's group performed a cross-sectional study of 100 patients who had experienced lupus flares or had persistently active disease.

The SLEDAI-2K was administered at the initial visit and then again after 1-3 months of treatment with prednisone and an immunosuppressant (hydroxychloroquine, azathioprine, methotrexate, or mycophenolate mofetil). The SRI-50 was also administered at the second visit.

Scores were calculated using a data retrieval form, with a range of scores from 1 (best) to 10 (worst) for each of the 24 descriptors. “It's very important to have a data retrieval form because if you are dealing with rash or arthritis you need a very accurate, standardized method of documentation,” he said.

For 72 patients, the SLEDAI-2K provided a satisfactory assessment at the second visit because their disease had either resolved completely or remained unchanged. However, for the remaining 28 patients, the SRI-50 signaled partial improvement that was undetected by the less-sensitive SLEDAI-2K. Among these patients, a 50% improvement was detected in 13 of the 24 descriptors and in six of the nine organ systems, said Dr. Touma.

Among these 28 patients, 90% were female, 53% were white, 16% were black, 10% were Chinese, and 21% were “other.” Their mean age at diagnosis was 32 years, and their mean duration of disease at first study visit was 13 years. Varying levels of disease activity were recorded at the first visit.

Three subjects had a SLEDAI-2K score of 2; three had a score of 4; six had a score of 6; six had a score of 8; three had a score of 10; two had a score of 12; one had a score of 16; one had a score of 18; two had a score of 20; and one had a score of 21.

Dr. Touma said the goal of the study was primarily to develop a more sensitive tool to measure outcomes in clinical trials. However, he believes the SRI-50 will also play an important role in clinical practice, where “it is always crucial to be able to show that a patient is responding to medical treatment.”