Bruce Jancin

SNOWMASS, COLO. – Neutrophil extracellular traps are a recently identified component of innate immunity shaping up as a potential driving force in systemic lupus erythematosus and small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies.

Many key questions about neutrophil extracellular traps (NETs) remain to be answered in the next few years. The most clinically relevant include these: Can suppression of abnormal NET formation improve systemic lupus erythematosus (SLE) or small-vessel vasculitis? And can NET activity – that is, the NETosis level – serve as a biomarker for disease activity in patients with these disabling autoimmune disorders?

NETosis is the process by which activated neutrophils undergo a unique, nonapoptotic form of cell death. Intracellular chromatin unwinds, the nuclear membrane disintegrates, and the plasma membrane opens. This allows extrusion of large, net-like strands comprised of chromatin fibers, antimicrobial proteins, elastase, myeloperoxidase, and defensins. These cast nets are capable of rapidly trapping a broad range of microbes. But microbes aren’t the only entities that can trigger NETosis; interferon alpha and tumor necrosis factor can activate netting neutrophils as well, Dr. Mary Beth Humphrey explained at the symposium.

It had long been recognized that neutrophils figure in the pathogenesis of SLE, but their precise role has remained unknown until quite recently. Then last year, separate groups of investigators reported that netting neutrophils activate the immune system in both adult and pediatric SLE.

"Our results support a model that positions this unique type of neutrophil death linked with plasmacytoid dendritic cell activation and type I interferon production at the core of SLE pathogenesis," said Dr. Gina S. Carcia-Romo and associates at the Baylor Institute for Immunology Research, Dallas (Sci. Transl. Med. 2011;3:73ra20).

Separately, investigators at Houston’s M.D. Anderson Cancer Center showed that a large percentage of SLE patients have high titer antibodies against NET proteins, including the antimicrobial protein LL37 and human neutrophil peptides. This results in formation of highly stable immunogenic complexes composed of these proteins plus self-DNA. In vitro, these immune complexes activate dendritic cells, causing release of large quantities of interferon alpha, which is part of the lupus signature in both adult and pediatric SLE. In contrast, neither healthy controls nor patients with scleroderma make antibodies against NETs (Sci. Transl.Med. 2011;3:73ra19).

The current thinking is that NETosis, under the wrong circumstances, results in the creation of stable self-DNA/antibody complexes that are recognized by B cells and shown to toll-like receptor 9, leading to formation of autoantibodies. The emerging picture is one of a vicious cycle of chronic autoimmunity. But there aren’t yet enough data to say which comes first in lupus: abnormal NETosis leading to excessive presentation of chromatin and nuclear antigens, or autoantigens triggering overexuberant NETosis.

"The innate immune scientist in me would like to believe that it’s the abnormal netting that starts the process in the right genetic background," confessed Dr. Humphrey of the University of Oklahoma at Oklahoma City.

Putting lupus aside, Dr. Humphrey noted that an international team of investigators from the University of California, San Francisco, and multiple German universities have reported that NETosis appears to trigger vasculitis and promotes the autoimmune response in patients with small-vessel vasculitis. They showed that ANCAs trigger NETosis, and the nets that are subsequently cast contain the autoantigens proteinase-3 and myeloperoxidase, which figure prominently in Wegener’s granulomatosis and microscopic polyangiitis, respectively.

Also, they demonstrated that NETs are deposited in the inflamed kidneys of individuals with small-vessel vasculitis. And they also offered the tantalizing observation that another autoinflammatory condition – psoriasis – can be driven by activated plasmacytoid dendritic cells in the presence of LL37, which, as it turns out, is highly expressed in the skin of psoriasis patients (Nat. Med. 2009;15:623-5).

How might NET formation be suppressed to the benefit of patients with SLE or vasculitis? NETosis is a process driven by reactive oxygen species. Potential strategies include administering reactive oxygen scavengers and blocking nicotinamide adenine dinucleotide phosphate oxidase, according to Dr. Humphrey.

She reported having no financial conflicts.

SNOWMASS, COLO. – Neutrophil extracellular traps are a recently identified component of innate immunity shaping up as a potential driving force in systemic lupus erythematosus and small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies.

Many key questions about neutrophil extracellular traps (NETs) remain to be answered in the next few years. The most clinically relevant include these: Can suppression of abnormal NET formation improve systemic lupus erythematosus (SLE) or small-vessel vasculitis? And can NET activity – that is, the NETosis level – serve as a biomarker for disease activity in patients with these disabling autoimmune disorders?

NETosis is the process by which activated neutrophils undergo a unique, nonapoptotic form of cell death. Intracellular chromatin unwinds, the nuclear membrane disintegrates, and the plasma membrane opens. This allows extrusion of large, net-like strands comprised of chromatin fibers, antimicrobial proteins, elastase, myeloperoxidase, and defensins. These cast nets are capable of rapidly trapping a broad range of microbes. But microbes aren’t the only entities that can trigger NETosis; interferon alpha and tumor necrosis factor can activate netting neutrophils as well, Dr. Mary Beth Humphrey explained at the symposium.

It had long been recognized that neutrophils figure in the pathogenesis of SLE, but their precise role has remained unknown until quite recently. Then last year, separate groups of investigators reported that netting neutrophils activate the immune system in both adult and pediatric SLE.

"Our results support a model that positions this unique type of neutrophil death linked with plasmacytoid dendritic cell activation and type I interferon production at the core of SLE pathogenesis," said Dr. Gina S. Carcia-Romo and associates at the Baylor Institute for Immunology Research, Dallas (Sci. Transl. Med. 2011;3:73ra20).

Separately, investigators at Houston’s M.D. Anderson Cancer Center showed that a large percentage of SLE patients have high titer antibodies against NET proteins, including the antimicrobial protein LL37 and human neutrophil peptides. This results in formation of highly stable immunogenic complexes composed of these proteins plus self-DNA. In vitro, these immune complexes activate dendritic cells, causing release of large quantities of interferon alpha, which is part of the lupus signature in both adult and pediatric SLE. In contrast, neither healthy controls nor patients with scleroderma make antibodies against NETs (Sci. Transl.Med. 2011;3:73ra19).

The current thinking is that NETosis, under the wrong circumstances, results in the creation of stable self-DNA/antibody complexes that are recognized by B cells and shown to toll-like receptor 9, leading to formation of autoantibodies. The emerging picture is one of a vicious cycle of chronic autoimmunity. But there aren’t yet enough data to say which comes first in lupus: abnormal NETosis leading to excessive presentation of chromatin and nuclear antigens, or autoantigens triggering overexuberant NETosis.

"The innate immune scientist in me would like to believe that it’s the abnormal netting that starts the process in the right genetic background," confessed Dr. Humphrey of the University of Oklahoma at Oklahoma City.

Putting lupus aside, Dr. Humphrey noted that an international team of investigators from the University of California, San Francisco, and multiple German universities have reported that NETosis appears to trigger vasculitis and promotes the autoimmune response in patients with small-vessel vasculitis. They showed that ANCAs trigger NETosis, and the nets that are subsequently cast contain the autoantigens proteinase-3 and myeloperoxidase, which figure prominently in Wegener’s granulomatosis and microscopic polyangiitis, respectively.

Also, they demonstrated that NETs are deposited in the inflamed kidneys of individuals with small-vessel vasculitis. And they also offered the tantalizing observation that another autoinflammatory condition – psoriasis – can be driven by activated plasmacytoid dendritic cells in the presence of LL37, which, as it turns out, is highly expressed in the skin of psoriasis patients (Nat. Med. 2009;15:623-5).

How might NET formation be suppressed to the benefit of patients with SLE or vasculitis? NETosis is a process driven by reactive oxygen species. Potential strategies include administering reactive oxygen scavengers and blocking nicotinamide adenine dinucleotide phosphate oxidase, according to Dr. Humphrey.

She reported having no financial conflicts.

SNOWMASS, COLO. – Neutrophil extracellular traps are a recently identified component of innate immunity shaping up as a potential driving force in systemic lupus erythematosus and small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies.

Many key questions about neutrophil extracellular traps (NETs) remain to be answered in the next few years. The most clinically relevant include these: Can suppression of abnormal NET formation improve systemic lupus erythematosus (SLE) or small-vessel vasculitis? And can NET activity – that is, the NETosis level – serve as a biomarker for disease activity in patients with these disabling autoimmune disorders?

NETosis is the process by which activated neutrophils undergo a unique, nonapoptotic form of cell death. Intracellular chromatin unwinds, the nuclear membrane disintegrates, and the plasma membrane opens. This allows extrusion of large, net-like strands comprised of chromatin fibers, antimicrobial proteins, elastase, myeloperoxidase, and defensins. These cast nets are capable of rapidly trapping a broad range of microbes. But microbes aren’t the only entities that can trigger NETosis; interferon alpha and tumor necrosis factor can activate netting neutrophils as well, Dr. Mary Beth Humphrey explained at the symposium.

It had long been recognized that neutrophils figure in the pathogenesis of SLE, but their precise role has remained unknown until quite recently. Then last year, separate groups of investigators reported that netting neutrophils activate the immune system in both adult and pediatric SLE.

"Our results support a model that positions this unique type of neutrophil death linked with plasmacytoid dendritic cell activation and type I interferon production at the core of SLE pathogenesis," said Dr. Gina S. Carcia-Romo and associates at the Baylor Institute for Immunology Research, Dallas (Sci. Transl. Med. 2011;3:73ra20).

Separately, investigators at Houston’s M.D. Anderson Cancer Center showed that a large percentage of SLE patients have high titer antibodies against NET proteins, including the antimicrobial protein LL37 and human neutrophil peptides. This results in formation of highly stable immunogenic complexes composed of these proteins plus self-DNA. In vitro, these immune complexes activate dendritic cells, causing release of large quantities of interferon alpha, which is part of the lupus signature in both adult and pediatric SLE. In contrast, neither healthy controls nor patients with scleroderma make antibodies against NETs (Sci. Transl.Med. 2011;3:73ra19).

The current thinking is that NETosis, under the wrong circumstances, results in the creation of stable self-DNA/antibody complexes that are recognized by B cells and shown to toll-like receptor 9, leading to formation of autoantibodies. The emerging picture is one of a vicious cycle of chronic autoimmunity. But there aren’t yet enough data to say which comes first in lupus: abnormal NETosis leading to excessive presentation of chromatin and nuclear antigens, or autoantigens triggering overexuberant NETosis.

"The innate immune scientist in me would like to believe that it’s the abnormal netting that starts the process in the right genetic background," confessed Dr. Humphrey of the University of Oklahoma at Oklahoma City.

Putting lupus aside, Dr. Humphrey noted that an international team of investigators from the University of California, San Francisco, and multiple German universities have reported that NETosis appears to trigger vasculitis and promotes the autoimmune response in patients with small-vessel vasculitis. They showed that ANCAs trigger NETosis, and the nets that are subsequently cast contain the autoantigens proteinase-3 and myeloperoxidase, which figure prominently in Wegener’s granulomatosis and microscopic polyangiitis, respectively.

Also, they demonstrated that NETs are deposited in the inflamed kidneys of individuals with small-vessel vasculitis. And they also offered the tantalizing observation that another autoinflammatory condition – psoriasis – can be driven by activated plasmacytoid dendritic cells in the presence of LL37, which, as it turns out, is highly expressed in the skin of psoriasis patients (Nat. Med. 2009;15:623-5).

How might NET formation be suppressed to the benefit of patients with SLE or vasculitis? NETosis is a process driven by reactive oxygen species. Potential strategies include administering reactive oxygen scavengers and blocking nicotinamide adenine dinucleotide phosphate oxidase, according to Dr. Humphrey.

She reported having no financial conflicts.

DENVER – Playing a musical instrument, singing, or simply listening to recorded music resulted in significant reduction in anxiety scores in patients with cancer, according to a Cochrane Database systematic review and meta-analysis.

The various music interventions offered by medical staff or trained music therapists also achieved significant improvements in the secondary end points of pain, mood, and quality of life scores, according to the review by investigators in the department of creative arts therapies at Drexel University in Philadelphia.

Photo Bruce Jancin/IMNG Medical Media

At the annual meeting of the American Academy of Hospice and Palliative Care Medicine, Dr. Wendy Anderson highlighted the Cochrane review findings as particularly on-point for her colleagues in oncology and palliative medicine.

"In palliative care we’re always trying to make the best of a difficult situation, and sometimes the best way to do this is through a nonpharmacologic intervention, even though it means doing something outside of our comfort zone," commented Dr. Anderson of the University of California, San Francisco.

Prior studies of music interventions in patients with cancer have been quite small. The Cochrane meta-analysis was designed to yield stronger, more definitive conclusions by incorporating those small studies which were sufficiently similar to combine.

The Cochrane report included 30 randomized clinical trials in seven countries with a total of 1,891 participating patients of all ages and with all types of cancer. In all, 13 trials involved the use of trained music therapists, while in the other 17 in the intervention consisted of listening to various genres of prerecorded music selected by the patients. Sessions were typically 30-45 minutes in length. The number of sessions varied widely from study to study. Subjects in the control arm received usual care or in some studies listened to white noise through headphones.

Sixteen randomized trials assessed anxiety. Collectively they showed that music interventions achieved statistically and clinically meaningful reductions in anxiety scores, with median to large effect sizes. For example, mean scores on the State Trait Anxiety Inventory fell by a mean of 11.2 units following the various music interventions while remaining unchanged in controls.

Similarly, the reduction in pain scores and improvements in structured measures of mood and quality of life in participants in the music interventions as compared to controls were also in the moderate to large range.

"Those are important outcomes in our patients with cancer," Dr. Anderson observed.

Music therapy is an established profession. Trained music therapists can perform a detailed patient evaluation and provide a tailored music experience. Although the Drexel researchers sought to learn whether the more elaborate, active participation music interventions provided by trained music therapists result in bigger improvements in psychologic and physical outcomes than the simpler music-listening interventions offered by medical staff, the investigators found that the research database wasn’t sufficiently large to draw any conclusions on that score (Cochrane Database Syst. Rev. 2011 [doi:10.1002/14651858.CD006911]).

The Cochrane group self-rated the quality of evidence on which the music intervention meta-analysis was based as low because these were nonblinded randomized trials. Patient awareness of whether they received a music intervention may have biased the results.

"Usually a low quality of evidence would, I think, make us reluctant to admit some innovations into our practices, but what’s interesting here is there’s a low potential for harm from music, and the patients feel the music improves their symptoms. That may be enough for us to implement music interventions in our practices," Dr. Anderson concluded.

The Cochrane review was funded by the State of Pennsylvania Formula Fund.

Dr. Anderson reported having no financial conflicts.

DENVER – Playing a musical instrument, singing, or simply listening to recorded music resulted in significant reduction in anxiety scores in patients with cancer, according to a Cochrane Database systematic review and meta-analysis.

The various music interventions offered by medical staff or trained music therapists also achieved significant improvements in the secondary end points of pain, mood, and quality of life scores, according to the review by investigators in the department of creative arts therapies at Drexel University in Philadelphia.

Photo Bruce Jancin/IMNG Medical Media

At the annual meeting of the American Academy of Hospice and Palliative Care Medicine, Dr. Wendy Anderson highlighted the Cochrane review findings as particularly on-point for her colleagues in oncology and palliative medicine.

"In palliative care we’re always trying to make the best of a difficult situation, and sometimes the best way to do this is through a nonpharmacologic intervention, even though it means doing something outside of our comfort zone," commented Dr. Anderson of the University of California, San Francisco.

Prior studies of music interventions in patients with cancer have been quite small. The Cochrane meta-analysis was designed to yield stronger, more definitive conclusions by incorporating those small studies which were sufficiently similar to combine.

The Cochrane report included 30 randomized clinical trials in seven countries with a total of 1,891 participating patients of all ages and with all types of cancer. In all, 13 trials involved the use of trained music therapists, while in the other 17 in the intervention consisted of listening to various genres of prerecorded music selected by the patients. Sessions were typically 30-45 minutes in length. The number of sessions varied widely from study to study. Subjects in the control arm received usual care or in some studies listened to white noise through headphones.

Sixteen randomized trials assessed anxiety. Collectively they showed that music interventions achieved statistically and clinically meaningful reductions in anxiety scores, with median to large effect sizes. For example, mean scores on the State Trait Anxiety Inventory fell by a mean of 11.2 units following the various music interventions while remaining unchanged in controls.

Similarly, the reduction in pain scores and improvements in structured measures of mood and quality of life in participants in the music interventions as compared to controls were also in the moderate to large range.

"Those are important outcomes in our patients with cancer," Dr. Anderson observed.

Music therapy is an established profession. Trained music therapists can perform a detailed patient evaluation and provide a tailored music experience. Although the Drexel researchers sought to learn whether the more elaborate, active participation music interventions provided by trained music therapists result in bigger improvements in psychologic and physical outcomes than the simpler music-listening interventions offered by medical staff, the investigators found that the research database wasn’t sufficiently large to draw any conclusions on that score (Cochrane Database Syst. Rev. 2011 [doi:10.1002/14651858.CD006911]).

The Cochrane group self-rated the quality of evidence on which the music intervention meta-analysis was based as low because these were nonblinded randomized trials. Patient awareness of whether they received a music intervention may have biased the results.

"Usually a low quality of evidence would, I think, make us reluctant to admit some innovations into our practices, but what’s interesting here is there’s a low potential for harm from music, and the patients feel the music improves their symptoms. That may be enough for us to implement music interventions in our practices," Dr. Anderson concluded.

The Cochrane review was funded by the State of Pennsylvania Formula Fund.

Dr. Anderson reported having no financial conflicts.

DENVER – Playing a musical instrument, singing, or simply listening to recorded music resulted in significant reduction in anxiety scores in patients with cancer, according to a Cochrane Database systematic review and meta-analysis.

The various music interventions offered by medical staff or trained music therapists also achieved significant improvements in the secondary end points of pain, mood, and quality of life scores, according to the review by investigators in the department of creative arts therapies at Drexel University in Philadelphia.

Photo Bruce Jancin/IMNG Medical Media

At the annual meeting of the American Academy of Hospice and Palliative Care Medicine, Dr. Wendy Anderson highlighted the Cochrane review findings as particularly on-point for her colleagues in oncology and palliative medicine.

"In palliative care we’re always trying to make the best of a difficult situation, and sometimes the best way to do this is through a nonpharmacologic intervention, even though it means doing something outside of our comfort zone," commented Dr. Anderson of the University of California, San Francisco.

Prior studies of music interventions in patients with cancer have been quite small. The Cochrane meta-analysis was designed to yield stronger, more definitive conclusions by incorporating those small studies which were sufficiently similar to combine.

The Cochrane report included 30 randomized clinical trials in seven countries with a total of 1,891 participating patients of all ages and with all types of cancer. In all, 13 trials involved the use of trained music therapists, while in the other 17 in the intervention consisted of listening to various genres of prerecorded music selected by the patients. Sessions were typically 30-45 minutes in length. The number of sessions varied widely from study to study. Subjects in the control arm received usual care or in some studies listened to white noise through headphones.

Sixteen randomized trials assessed anxiety. Collectively they showed that music interventions achieved statistically and clinically meaningful reductions in anxiety scores, with median to large effect sizes. For example, mean scores on the State Trait Anxiety Inventory fell by a mean of 11.2 units following the various music interventions while remaining unchanged in controls.

Similarly, the reduction in pain scores and improvements in structured measures of mood and quality of life in participants in the music interventions as compared to controls were also in the moderate to large range.

"Those are important outcomes in our patients with cancer," Dr. Anderson observed.

Music therapy is an established profession. Trained music therapists can perform a detailed patient evaluation and provide a tailored music experience. Although the Drexel researchers sought to learn whether the more elaborate, active participation music interventions provided by trained music therapists result in bigger improvements in psychologic and physical outcomes than the simpler music-listening interventions offered by medical staff, the investigators found that the research database wasn’t sufficiently large to draw any conclusions on that score (Cochrane Database Syst. Rev. 2011 [doi:10.1002/14651858.CD006911]).

The Cochrane group self-rated the quality of evidence on which the music intervention meta-analysis was based as low because these were nonblinded randomized trials. Patient awareness of whether they received a music intervention may have biased the results.

"Usually a low quality of evidence would, I think, make us reluctant to admit some innovations into our practices, but what’s interesting here is there’s a low potential for harm from music, and the patients feel the music improves their symptoms. That may be enough for us to implement music interventions in our practices," Dr. Anderson concluded.

The Cochrane review was funded by the State of Pennsylvania Formula Fund.

Dr. Anderson reported having no financial conflicts.

DENVER – Compounded ABH gel is widely prescribed for treatment of nausea in the hospice setting. It costs less than $1 per dose. Side effects are rare. And many clinicians swear by its effectiveness, noting that the constituent medications in ABH gel – Ativan (lorazepam), Benadryl (diphenhydramine), and Haldol (haloperidol) – target different mechanisms of nausea.

There is, however, a fly in the ointment ... er, gel.

It turns out that none of the three medications in topical ABH gel are absorbed systemically in anything remotely approaching therapeutic levels, Dr. Devon S. Fletcher reported at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

"Either ABH gel doesn’t work, or the effect is attributable to placebo, or possibly a nonpharmacologic mechanism is involved, such as stimulation of the P6 acupressure point on the wrist as patients rub the gel in," said Dr. Fletcher of Virginia Commonwealth University, Richmond. "If ABH doesn’t work, using it to treat a symptom leads to unacceptable suffering and unnecessary hospitalizations," she added.

Dr. Fletcher and coworkers measured levels of the three medications contained in ABH gel in six blood samples taken serially in each of 10 healthy volunteers up to 4 hours after they rubbed 1 mL of the gel between their volar wrists for 2 minutes. That’s the standard means of administering the medication, which is self-applied every 4-6 hours in clinical practice. A 1-mL dose contains 2 mg of lorazepam, 25 mg of diphenhydramine, and 2 mg of haloperidol compounded using a popular published formula.

Both lorazepam and haloperidol were undetectable in blood samples at all times in all 10 subjects; the medications never made it past the skin barrier. The highest concentration of diphenhydramine, reached in only a single patient, was 0.3 ng at 4 hours. That translates to 0.0003 mcg/mL, roughly 1/1000th of the therapeutic level, she noted.

The study was undertaken as a prelude to a planned single-center, randomized, placebo-controlled, crossover clinical trial of ABH gel in hospice patients with nausea. Dr. Fletcher and coinvestigators still plan to conduct that trial because ABH gel has never been subjected to a prospective controlled study.

"This is a wake-up call that we need further testing and evaluation before introducing treatments into widespread use," the physician declared.

Several audience members rose to applaud Dr. Fletcher for what they called a long-overdue rigorous look at an extremely popular yet unexamined therapy. One physician said he’d also like to see placebo-controlled studies of phenobarbital and dexamethasone for nausea, as these agents are widely prescribed but lacking in solid data supporting efficacy. He added that his own anecdotal experience with those two drugs as antiemetic agents in the hospice setting has been disappointing.

Dr. Fletcher reported having no financial conflicts.

DENVER – Compounded ABH gel is widely prescribed for treatment of nausea in the hospice setting. It costs less than $1 per dose. Side effects are rare. And many clinicians swear by its effectiveness, noting that the constituent medications in ABH gel – Ativan (lorazepam), Benadryl (diphenhydramine), and Haldol (haloperidol) – target different mechanisms of nausea.

There is, however, a fly in the ointment ... er, gel.

It turns out that none of the three medications in topical ABH gel are absorbed systemically in anything remotely approaching therapeutic levels, Dr. Devon S. Fletcher reported at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

"Either ABH gel doesn’t work, or the effect is attributable to placebo, or possibly a nonpharmacologic mechanism is involved, such as stimulation of the P6 acupressure point on the wrist as patients rub the gel in," said Dr. Fletcher of Virginia Commonwealth University, Richmond. "If ABH doesn’t work, using it to treat a symptom leads to unacceptable suffering and unnecessary hospitalizations," she added.

Dr. Fletcher and coworkers measured levels of the three medications contained in ABH gel in six blood samples taken serially in each of 10 healthy volunteers up to 4 hours after they rubbed 1 mL of the gel between their volar wrists for 2 minutes. That’s the standard means of administering the medication, which is self-applied every 4-6 hours in clinical practice. A 1-mL dose contains 2 mg of lorazepam, 25 mg of diphenhydramine, and 2 mg of haloperidol compounded using a popular published formula.

Both lorazepam and haloperidol were undetectable in blood samples at all times in all 10 subjects; the medications never made it past the skin barrier. The highest concentration of diphenhydramine, reached in only a single patient, was 0.3 ng at 4 hours. That translates to 0.0003 mcg/mL, roughly 1/1000th of the therapeutic level, she noted.

The study was undertaken as a prelude to a planned single-center, randomized, placebo-controlled, crossover clinical trial of ABH gel in hospice patients with nausea. Dr. Fletcher and coinvestigators still plan to conduct that trial because ABH gel has never been subjected to a prospective controlled study.

"This is a wake-up call that we need further testing and evaluation before introducing treatments into widespread use," the physician declared.

Several audience members rose to applaud Dr. Fletcher for what they called a long-overdue rigorous look at an extremely popular yet unexamined therapy. One physician said he’d also like to see placebo-controlled studies of phenobarbital and dexamethasone for nausea, as these agents are widely prescribed but lacking in solid data supporting efficacy. He added that his own anecdotal experience with those two drugs as antiemetic agents in the hospice setting has been disappointing.

Dr. Fletcher reported having no financial conflicts.

DENVER – Compounded ABH gel is widely prescribed for treatment of nausea in the hospice setting. It costs less than $1 per dose. Side effects are rare. And many clinicians swear by its effectiveness, noting that the constituent medications in ABH gel – Ativan (lorazepam), Benadryl (diphenhydramine), and Haldol (haloperidol) – target different mechanisms of nausea.

There is, however, a fly in the ointment ... er, gel.

It turns out that none of the three medications in topical ABH gel are absorbed systemically in anything remotely approaching therapeutic levels, Dr. Devon S. Fletcher reported at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

"Either ABH gel doesn’t work, or the effect is attributable to placebo, or possibly a nonpharmacologic mechanism is involved, such as stimulation of the P6 acupressure point on the wrist as patients rub the gel in," said Dr. Fletcher of Virginia Commonwealth University, Richmond. "If ABH doesn’t work, using it to treat a symptom leads to unacceptable suffering and unnecessary hospitalizations," she added.

Dr. Fletcher and coworkers measured levels of the three medications contained in ABH gel in six blood samples taken serially in each of 10 healthy volunteers up to 4 hours after they rubbed 1 mL of the gel between their volar wrists for 2 minutes. That’s the standard means of administering the medication, which is self-applied every 4-6 hours in clinical practice. A 1-mL dose contains 2 mg of lorazepam, 25 mg of diphenhydramine, and 2 mg of haloperidol compounded using a popular published formula.

Both lorazepam and haloperidol were undetectable in blood samples at all times in all 10 subjects; the medications never made it past the skin barrier. The highest concentration of diphenhydramine, reached in only a single patient, was 0.3 ng at 4 hours. That translates to 0.0003 mcg/mL, roughly 1/1000th of the therapeutic level, she noted.

The study was undertaken as a prelude to a planned single-center, randomized, placebo-controlled, crossover clinical trial of ABH gel in hospice patients with nausea. Dr. Fletcher and coinvestigators still plan to conduct that trial because ABH gel has never been subjected to a prospective controlled study.

"This is a wake-up call that we need further testing and evaluation before introducing treatments into widespread use," the physician declared.

Several audience members rose to applaud Dr. Fletcher for what they called a long-overdue rigorous look at an extremely popular yet unexamined therapy. One physician said he’d also like to see placebo-controlled studies of phenobarbital and dexamethasone for nausea, as these agents are widely prescribed but lacking in solid data supporting efficacy. He added that his own anecdotal experience with those two drugs as antiemetic agents in the hospice setting has been disappointing.

Dr. Fletcher reported having no financial conflicts.

SNOWMASS, COLO. – Nondermatologists often have a dickens of a time differentiating the malar rash that’s a hallmark of systemic lupus erythematosus from butterfly midfacial rashes due to other diseases, most notably rosacea and dermatomyositis. Dr. Ruth Ann Vleugels has provided some useful tips.

The malar rash of systemic lupus erythematosus (SLE) consistently spares the nasolabial folds, for reasons unknown. So, if a red, butterfly-shaped rash on the central face involves the nasolabial area, it’s not SLE, she explained at the symposium.

In contrast, when the erythrotelangiectatic or papulopustular variants of rosacea blanket the midface with a rash that looks much like the malar rash of SLE, the nasolabial area is included, not spared.

"Rosacea with a rash on the malar area and photosensitivity are very common in young, fair-skinned women, as is lupus. These patients with rosacea often get [antinuclear antibody (ANA)] testing. A lot of them will be positive, so already they have three ACR criteria for SLE, and they end up in your office," said Dr. Vleugels, a dermatologist who is director of the connective tissue disease clinic at Brigham and Women’s Hospital and codirector of the rheumatology-dermatology clinic at Children’s Hospital, Boston.

Alopecia and hemorrhagic crusting on the lips are common in patients with SLE, not so in rosacea. Also, patients who present with rosacea are usually in general good health, whereas those with the malar rash of SLE often feel sick and have systemic findings at presentation.

It’s helpful to ask whether the patient has noticed if the rash has other triggers in addition to sunlight. Alcohol and spicy foods are two of the most common ones in rosacea.

Midfacial erythema that includes rather than spares the nasolabial folds is also a characteristic finding in dermatomyositis. Nailfold findings provide another important cutaneous clue to the diagnosis of dermatomyositis. The changes to look for are dilated capillary loops, thrombosed capillary loops, capillary dropout, and cuticular hypertrophy.

The shawl sign – a diffuse, flat erythema on the upper back and chest – is another clue suggestive of dermatomyositis. The eruption is inflammatory early on and more atrophic later.

Mechanics’ hands, with cracked skin at the tips of the fingers, is another skin finding in dermatomyositis, Dr. Vleugels continued.

A poikiloderma known as the holster sign, so named because of its location on the lateral upper thigh, is a common finding in dermatomyositis patients. The sun-protected location is something of a mystery given that dermatomyositis is a photo-exacerbated disease.

Scalp disease is extremely common in patients with dermatomyositis, and it is strikingly pruritic.

A heliotropic skin eruption and Gottron\'s papules are considered pathognomic for dermatomyositis, but these can be tricky. The heliotrope rash is classically a prominent violaceous erythema on the eyelids; however, it’s often a subtle abnormality that waxes and wanes. And the classic violaceous Gottron’s papules found only over the knuckles are tough to detect in darker skinned patients. When Gottron’s papules are scaly they can be misdiagnosed as psoriasis. Dr. Vleugels has even seen them misdiagnosed and treated as warts.

Skin biopsy is typically of little value in differentiating lupus from dermatomyositis. The pathology report can be the same in both conditions: vacuolar interface changes at the basement membrane, with mucin in the dermis.

"If the report reads ‘lupus’ you always have to put dermatomyositis in the differential diagnosis, and the decision is a purely clinical one," Dr. Vleugels advised.

She reported having no financial conflicts.

SNOWMASS, COLO. – Nondermatologists often have a dickens of a time differentiating the malar rash that’s a hallmark of systemic lupus erythematosus from butterfly midfacial rashes due to other diseases, most notably rosacea and dermatomyositis. Dr. Ruth Ann Vleugels has provided some useful tips.

The malar rash of systemic lupus erythematosus (SLE) consistently spares the nasolabial folds, for reasons unknown. So, if a red, butterfly-shaped rash on the central face involves the nasolabial area, it’s not SLE, she explained at the symposium.

In contrast, when the erythrotelangiectatic or papulopustular variants of rosacea blanket the midface with a rash that looks much like the malar rash of SLE, the nasolabial area is included, not spared.

"Rosacea with a rash on the malar area and photosensitivity are very common in young, fair-skinned women, as is lupus. These patients with rosacea often get [antinuclear antibody (ANA)] testing. A lot of them will be positive, so already they have three ACR criteria for SLE, and they end up in your office," said Dr. Vleugels, a dermatologist who is director of the connective tissue disease clinic at Brigham and Women’s Hospital and codirector of the rheumatology-dermatology clinic at Children’s Hospital, Boston.

Alopecia and hemorrhagic crusting on the lips are common in patients with SLE, not so in rosacea. Also, patients who present with rosacea are usually in general good health, whereas those with the malar rash of SLE often feel sick and have systemic findings at presentation.

It’s helpful to ask whether the patient has noticed if the rash has other triggers in addition to sunlight. Alcohol and spicy foods are two of the most common ones in rosacea.

Midfacial erythema that includes rather than spares the nasolabial folds is also a characteristic finding in dermatomyositis. Nailfold findings provide another important cutaneous clue to the diagnosis of dermatomyositis. The changes to look for are dilated capillary loops, thrombosed capillary loops, capillary dropout, and cuticular hypertrophy.

The shawl sign – a diffuse, flat erythema on the upper back and chest – is another clue suggestive of dermatomyositis. The eruption is inflammatory early on and more atrophic later.

Mechanics’ hands, with cracked skin at the tips of the fingers, is another skin finding in dermatomyositis, Dr. Vleugels continued.

A poikiloderma known as the holster sign, so named because of its location on the lateral upper thigh, is a common finding in dermatomyositis patients. The sun-protected location is something of a mystery given that dermatomyositis is a photo-exacerbated disease.

Scalp disease is extremely common in patients with dermatomyositis, and it is strikingly pruritic.

A heliotropic skin eruption and Gottron\'s papules are considered pathognomic for dermatomyositis, but these can be tricky. The heliotrope rash is classically a prominent violaceous erythema on the eyelids; however, it’s often a subtle abnormality that waxes and wanes. And the classic violaceous Gottron’s papules found only over the knuckles are tough to detect in darker skinned patients. When Gottron’s papules are scaly they can be misdiagnosed as psoriasis. Dr. Vleugels has even seen them misdiagnosed and treated as warts.

Skin biopsy is typically of little value in differentiating lupus from dermatomyositis. The pathology report can be the same in both conditions: vacuolar interface changes at the basement membrane, with mucin in the dermis.

"If the report reads ‘lupus’ you always have to put dermatomyositis in the differential diagnosis, and the decision is a purely clinical one," Dr. Vleugels advised.

She reported having no financial conflicts.

SNOWMASS, COLO. – Nondermatologists often have a dickens of a time differentiating the malar rash that’s a hallmark of systemic lupus erythematosus from butterfly midfacial rashes due to other diseases, most notably rosacea and dermatomyositis. Dr. Ruth Ann Vleugels has provided some useful tips.

The malar rash of systemic lupus erythematosus (SLE) consistently spares the nasolabial folds, for reasons unknown. So, if a red, butterfly-shaped rash on the central face involves the nasolabial area, it’s not SLE, she explained at the symposium.

In contrast, when the erythrotelangiectatic or papulopustular variants of rosacea blanket the midface with a rash that looks much like the malar rash of SLE, the nasolabial area is included, not spared.

"Rosacea with a rash on the malar area and photosensitivity are very common in young, fair-skinned women, as is lupus. These patients with rosacea often get [antinuclear antibody (ANA)] testing. A lot of them will be positive, so already they have three ACR criteria for SLE, and they end up in your office," said Dr. Vleugels, a dermatologist who is director of the connective tissue disease clinic at Brigham and Women’s Hospital and codirector of the rheumatology-dermatology clinic at Children’s Hospital, Boston.

Alopecia and hemorrhagic crusting on the lips are common in patients with SLE, not so in rosacea. Also, patients who present with rosacea are usually in general good health, whereas those with the malar rash of SLE often feel sick and have systemic findings at presentation.

It’s helpful to ask whether the patient has noticed if the rash has other triggers in addition to sunlight. Alcohol and spicy foods are two of the most common ones in rosacea.

Midfacial erythema that includes rather than spares the nasolabial folds is also a characteristic finding in dermatomyositis. Nailfold findings provide another important cutaneous clue to the diagnosis of dermatomyositis. The changes to look for are dilated capillary loops, thrombosed capillary loops, capillary dropout, and cuticular hypertrophy.

The shawl sign – a diffuse, flat erythema on the upper back and chest – is another clue suggestive of dermatomyositis. The eruption is inflammatory early on and more atrophic later.

Mechanics’ hands, with cracked skin at the tips of the fingers, is another skin finding in dermatomyositis, Dr. Vleugels continued.

A poikiloderma known as the holster sign, so named because of its location on the lateral upper thigh, is a common finding in dermatomyositis patients. The sun-protected location is something of a mystery given that dermatomyositis is a photo-exacerbated disease.

Scalp disease is extremely common in patients with dermatomyositis, and it is strikingly pruritic.

A heliotropic skin eruption and Gottron\'s papules are considered pathognomic for dermatomyositis, but these can be tricky. The heliotrope rash is classically a prominent violaceous erythema on the eyelids; however, it’s often a subtle abnormality that waxes and wanes. And the classic violaceous Gottron’s papules found only over the knuckles are tough to detect in darker skinned patients. When Gottron’s papules are scaly they can be misdiagnosed as psoriasis. Dr. Vleugels has even seen them misdiagnosed and treated as warts.

Skin biopsy is typically of little value in differentiating lupus from dermatomyositis. The pathology report can be the same in both conditions: vacuolar interface changes at the basement membrane, with mucin in the dermis.

"If the report reads ‘lupus’ you always have to put dermatomyositis in the differential diagnosis, and the decision is a purely clinical one," Dr. Vleugels advised.

She reported having no financial conflicts.

WAIKOLOA, HAWAII  – The androgen receptor–blocker spironolactone is highly effective and safe but underused for the treatment of acne in women, according to Dr. Julie C. Harper.

"The longer I’ve been in practice, the wider the age range where I use spironolactone as my drug of choice," Dr. Harper said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Spironolactone is her first-line therapy for acne in postmenopausal women and in those who have had a hysterectomy. In such patients "it’s a really great drug to use by itself" because the women can’t get pregnant; the drug has a pregnancy category C rating, with an associated risk of feminization of a male fetus exposed to the drug late in the first trimester, explained Dr. Harper, a dermatologist at the University of Alabama, Birmingham.

"I have a tendency in my practice to start with an oral contraceptive in women of child-bearing potential and then maybe add spironolactone if I need to," she said.

However, Dr. Harper said that she will turn to spironolactone in women as young as 16 years of age with a contraindication to OCs. First, however, she carefully explains that the drug is safe as long as they don’t take it when pregnant. Spironolactone also cannot be used by nursing mothers because the drug’s major metabolite, canrenone, has been detected in breast milk.

Acne is a common problem in women. A survey of 1,013 adults in which Dr. Harper was a coinvestigator concluded that the prevalence of acne was significantly greater in women than men across all age groups. For example, the prevalence was 26% among 40- to 49-year-old women, compared with 12% in men of the same age, and 15% among women age 50-plus, compared to 7% in men (J. Am. Acad. Dermatol. 2008;58:56-9).

Acne is not only more common in women than men, it also differs in its characteristic presentation, which in women is typically lower-face acne in a U-shaped distribution.

Most women with adult acne have normal levels of circulating androgens. A leading hypothesis holds that their acne is the result of end-organ hyper-responsiveness to androgens. Androgen receptors are present in the sebaceous glands and the follicular wall, where comedones develop. This would explain why spironolactone is so effective clinically; the drug not only blocks the androgen receptor, it also reduces androgen synthesis in the adrenal gland and gonads, Dr. Harper noted.

She prescribes spironolactone in lower-range doses of 25-100 mg/day. At those doses she doesn’t bother to check serum potassium levels in relatively healthy young women so long as they’re not on other medications that may cause hyperkalemia, such as ACE inhibitors or chronic NSAIDs.

"You get good efficacy with fewer side effects at a maximum dose of 100 mg," according to the dermatologist.

Concomitant use of an OC lessens the menstrual irregularities and breast tenderness that can occur as side effects of spironolactone therapy. All combination OCs are probably effective in the treatment of acne. Four are approved for this indication: Ortho Tri-Cyclen, Estrostep, YAZ, and Beyaz.

Spironolactone should be thought of as long-term therapy. When spironolactone or an OC prescribed for adult acne is stopped, it’s highly likely that the acne will return within several months.

"When I plan to use spironolactone, I tell my patients they’re going to be on this for a long time if it works," Dr. Harper said.

The Food and Drug Administration has a long-standing Black Box Warning regarding spironolactone. Such warnings can send a chill down the spine of physicians and patients alike. However, there are widespread misconceptions about what this particular warning actually says. Here it is: "Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Spironolactone should be used only in those conditions described under Indications and Usage. Unnecessary use of this drug should be avoided."

The dosages used in those rat studies, by the way, were 25-100 times higher than those used in patients therapeutically.

"So we’re talking about rats, we’re talking about benign tumors, and we’re talking about super-duper high doses. That’s what’s in the Black Box Warning for spironolactone," she said.

Spironolactone is off-label therapy for acne, a point that caused another speaker at the seminar to bristle.

"If we used medications only for their approved indications, we couldn’t practice two-thirds of what we do," declared Dr. Theodore Rosen, professor of dermatology at Baylor College of Medicine, Houston.

"The FDA has said they’re not in the business of dictating how you practice medicine," he added. "You can use any approved drug in any fashion if you have some reasonable justification for it. If a plaintiff’s lawyer claims ‘This doctor used spironolactone off-label,’ she could line up 100 experts who’d say this is standard-of-care, and the standard of care determines what’s right and what’s wrong."

Dr. Harper is on the speakers bureaus for Allergan, Coria, Galderma, Intendis, Medicis, and Stiefel.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII  – The androgen receptor–blocker spironolactone is highly effective and safe but underused for the treatment of acne in women, according to Dr. Julie C. Harper.

"The longer I’ve been in practice, the wider the age range where I use spironolactone as my drug of choice," Dr. Harper said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Spironolactone is her first-line therapy for acne in postmenopausal women and in those who have had a hysterectomy. In such patients "it’s a really great drug to use by itself" because the women can’t get pregnant; the drug has a pregnancy category C rating, with an associated risk of feminization of a male fetus exposed to the drug late in the first trimester, explained Dr. Harper, a dermatologist at the University of Alabama, Birmingham.

"I have a tendency in my practice to start with an oral contraceptive in women of child-bearing potential and then maybe add spironolactone if I need to," she said.

However, Dr. Harper said that she will turn to spironolactone in women as young as 16 years of age with a contraindication to OCs. First, however, she carefully explains that the drug is safe as long as they don’t take it when pregnant. Spironolactone also cannot be used by nursing mothers because the drug’s major metabolite, canrenone, has been detected in breast milk.

Acne is a common problem in women. A survey of 1,013 adults in which Dr. Harper was a coinvestigator concluded that the prevalence of acne was significantly greater in women than men across all age groups. For example, the prevalence was 26% among 40- to 49-year-old women, compared with 12% in men of the same age, and 15% among women age 50-plus, compared to 7% in men (J. Am. Acad. Dermatol. 2008;58:56-9).

Acne is not only more common in women than men, it also differs in its characteristic presentation, which in women is typically lower-face acne in a U-shaped distribution.

Most women with adult acne have normal levels of circulating androgens. A leading hypothesis holds that their acne is the result of end-organ hyper-responsiveness to androgens. Androgen receptors are present in the sebaceous glands and the follicular wall, where comedones develop. This would explain why spironolactone is so effective clinically; the drug not only blocks the androgen receptor, it also reduces androgen synthesis in the adrenal gland and gonads, Dr. Harper noted.

She prescribes spironolactone in lower-range doses of 25-100 mg/day. At those doses she doesn’t bother to check serum potassium levels in relatively healthy young women so long as they’re not on other medications that may cause hyperkalemia, such as ACE inhibitors or chronic NSAIDs.

"You get good efficacy with fewer side effects at a maximum dose of 100 mg," according to the dermatologist.

Concomitant use of an OC lessens the menstrual irregularities and breast tenderness that can occur as side effects of spironolactone therapy. All combination OCs are probably effective in the treatment of acne. Four are approved for this indication: Ortho Tri-Cyclen, Estrostep, YAZ, and Beyaz.

Spironolactone should be thought of as long-term therapy. When spironolactone or an OC prescribed for adult acne is stopped, it’s highly likely that the acne will return within several months.

"When I plan to use spironolactone, I tell my patients they’re going to be on this for a long time if it works," Dr. Harper said.

The Food and Drug Administration has a long-standing Black Box Warning regarding spironolactone. Such warnings can send a chill down the spine of physicians and patients alike. However, there are widespread misconceptions about what this particular warning actually says. Here it is: "Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Spironolactone should be used only in those conditions described under Indications and Usage. Unnecessary use of this drug should be avoided."

The dosages used in those rat studies, by the way, were 25-100 times higher than those used in patients therapeutically.

"So we’re talking about rats, we’re talking about benign tumors, and we’re talking about super-duper high doses. That’s what’s in the Black Box Warning for spironolactone," she said.

Spironolactone is off-label therapy for acne, a point that caused another speaker at the seminar to bristle.

"If we used medications only for their approved indications, we couldn’t practice two-thirds of what we do," declared Dr. Theodore Rosen, professor of dermatology at Baylor College of Medicine, Houston.

"The FDA has said they’re not in the business of dictating how you practice medicine," he added. "You can use any approved drug in any fashion if you have some reasonable justification for it. If a plaintiff’s lawyer claims ‘This doctor used spironolactone off-label,’ she could line up 100 experts who’d say this is standard-of-care, and the standard of care determines what’s right and what’s wrong."

Dr. Harper is on the speakers bureaus for Allergan, Coria, Galderma, Intendis, Medicis, and Stiefel.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII  – The androgen receptor–blocker spironolactone is highly effective and safe but underused for the treatment of acne in women, according to Dr. Julie C. Harper.

"The longer I’ve been in practice, the wider the age range where I use spironolactone as my drug of choice," Dr. Harper said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

Spironolactone is her first-line therapy for acne in postmenopausal women and in those who have had a hysterectomy. In such patients "it’s a really great drug to use by itself" because the women can’t get pregnant; the drug has a pregnancy category C rating, with an associated risk of feminization of a male fetus exposed to the drug late in the first trimester, explained Dr. Harper, a dermatologist at the University of Alabama, Birmingham.

"I have a tendency in my practice to start with an oral contraceptive in women of child-bearing potential and then maybe add spironolactone if I need to," she said.

However, Dr. Harper said that she will turn to spironolactone in women as young as 16 years of age with a contraindication to OCs. First, however, she carefully explains that the drug is safe as long as they don’t take it when pregnant. Spironolactone also cannot be used by nursing mothers because the drug’s major metabolite, canrenone, has been detected in breast milk.

Acne is a common problem in women. A survey of 1,013 adults in which Dr. Harper was a coinvestigator concluded that the prevalence of acne was significantly greater in women than men across all age groups. For example, the prevalence was 26% among 40- to 49-year-old women, compared with 12% in men of the same age, and 15% among women age 50-plus, compared to 7% in men (J. Am. Acad. Dermatol. 2008;58:56-9).

Acne is not only more common in women than men, it also differs in its characteristic presentation, which in women is typically lower-face acne in a U-shaped distribution.

Most women with adult acne have normal levels of circulating androgens. A leading hypothesis holds that their acne is the result of end-organ hyper-responsiveness to androgens. Androgen receptors are present in the sebaceous glands and the follicular wall, where comedones develop. This would explain why spironolactone is so effective clinically; the drug not only blocks the androgen receptor, it also reduces androgen synthesis in the adrenal gland and gonads, Dr. Harper noted.

She prescribes spironolactone in lower-range doses of 25-100 mg/day. At those doses she doesn’t bother to check serum potassium levels in relatively healthy young women so long as they’re not on other medications that may cause hyperkalemia, such as ACE inhibitors or chronic NSAIDs.

"You get good efficacy with fewer side effects at a maximum dose of 100 mg," according to the dermatologist.

Concomitant use of an OC lessens the menstrual irregularities and breast tenderness that can occur as side effects of spironolactone therapy. All combination OCs are probably effective in the treatment of acne. Four are approved for this indication: Ortho Tri-Cyclen, Estrostep, YAZ, and Beyaz.

Spironolactone should be thought of as long-term therapy. When spironolactone or an OC prescribed for adult acne is stopped, it’s highly likely that the acne will return within several months.

"When I plan to use spironolactone, I tell my patients they’re going to be on this for a long time if it works," Dr. Harper said.

The Food and Drug Administration has a long-standing Black Box Warning regarding spironolactone. Such warnings can send a chill down the spine of physicians and patients alike. However, there are widespread misconceptions about what this particular warning actually says. Here it is: "Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Spironolactone should be used only in those conditions described under Indications and Usage. Unnecessary use of this drug should be avoided."

The dosages used in those rat studies, by the way, were 25-100 times higher than those used in patients therapeutically.

"So we’re talking about rats, we’re talking about benign tumors, and we’re talking about super-duper high doses. That’s what’s in the Black Box Warning for spironolactone," she said.

Spironolactone is off-label therapy for acne, a point that caused another speaker at the seminar to bristle.

"If we used medications only for their approved indications, we couldn’t practice two-thirds of what we do," declared Dr. Theodore Rosen, professor of dermatology at Baylor College of Medicine, Houston.

"The FDA has said they’re not in the business of dictating how you practice medicine," he added. "You can use any approved drug in any fashion if you have some reasonable justification for it. If a plaintiff’s lawyer claims ‘This doctor used spironolactone off-label,’ she could line up 100 experts who’d say this is standard-of-care, and the standard of care determines what’s right and what’s wrong."

Dr. Harper is on the speakers bureaus for Allergan, Coria, Galderma, Intendis, Medicis, and Stiefel.

SDEF and this news organization are owned by Elsevier.

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

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

Bruce Jancin/IMNG Medical Media

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

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

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

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

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

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

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

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

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

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

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

He reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

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

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

Bruce Jancin/IMNG Medical Media

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

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

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

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

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

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

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

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

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

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

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

He reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

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

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

Bruce Jancin/IMNG Medical Media

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

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

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

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

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

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

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

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

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

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

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

He reported having no financial conflicts.

SDEF and this news organization are owned by Elsevier.

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

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

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

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

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

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

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

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

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

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

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

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

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

He reported having no financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

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

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

He reported having no financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

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

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

He reported having no financial conflicts.

SNOWMASS, COLO. – Serial pulmonary function testing, including diffusion capacity, is routinely warranted – but all too often overlooked – in patients with skin-predominant dermatomyositis.

It’s not widely appreciated that patients with clinically amyopathic dermatomyositis and those with classic dermatomyositis are at similarly high risk for developing interstitial lung disease, Dr. Ruth Ann Vleugels observed at a symposium sponsored by the American College of Rheumatology.

"I often see patients with clinically amyopathic dermatomyositis who are assumed to have skin-limited disease and have never had pulmonary function tests. All these patients really should have serial pulmonary function tests with diffusion capacity studies. This is probably what’s most often forgotten, particularly in the evaluation of our amyopathic patients," declared Dr. Vleugels, a dermatologist who is director of the connective tissue disease clinic at Brigham and Women’s Hospital in Boston and codirector of the rheumatology-dermatology clinic at Children’s Hospital Boston.

She added that patients with amyopathic dermatomyositis, like those with classic dermatomyositis, are also at elevated risk for internal malignancy.

"The take-home message is, clinically amyopathic patients can have cancer and interstitial lung disease. So even though they don’t have muscle disease, we need to screen identically for malignancy and also work them up for interstitial lung disease," the dermatologist continued.

Dr. Vleugels highlighted a retrospective study by investigators at the University of Pennsylvania in Philadelphia that underscored the similarly high risk of interstitial lung disease (ILD) in patients with skin-predominant and classic dermatomyositis.

The study involved 71 patients with dermatomyositis who were screened for ILD via thin-slice chest CT scans and pulmonary function testing that included diffusing capacity for carbon monoxide (DLCO). In all, 35 patients had clinically amyopathic dermatomyositis (a condition formerly known as dermatomyositis sine myositis) and 36 had the classic form of the disease featuring muscle involvement.

The overall prevalence of ILD by CT scan was 23%. The pulmonary disease was present in 10 of 35 patients with clinically amyopathic dermatomyositis and in 6 of 36 subjects with the classic form of dermatomyositis featuring muscle involvement, rates that were not significantly different (Arch. Dermatol. 2010;146:729-38).

All dermatomyositis patients with ILD had a reduced DLCO. In addition, 7 of 35 with clinically amyopathic dermatomyositis and 11 of 36 with classic dermatomyositis had a low DLCO in the absence of CT evidence of ILD. The clinical implication of such findings remains unclear. It may be that an isolated low DLCO with a normal chest CT is an indication of early ILD, or perhaps pulmonary hypertension, but a larger study with longer follow-up will be required to learn whether, in fact, an isolated low DLCO in the setting of dermatomyositis predicts progression to restrictive lung disease.

Because all patients in this study with CT evidence of ILD also had a low DLCO, the investigators recommended that all dermatomyositis patients routinely undergo serial screening with pulmonary function tests. Those with a moderate or severe reduction in DLCO (that is, less than 61% of the predicted value) should undergo thin-slice CT and referral to a pulmonologist for further management.

Dermatomyositis patients with a mildly low DLCO (defined as 61%-75% of predicted) should also have a high-resolution chest CT, as well as echocardiography to rule out pulmonary hypertension. If these studies prove negative, close follow-up with serial pulmonary function tests as well as inquiry regarding the clinical symptoms of shortness of breath and cough is appropriate, according to the Penn investigators.

Dr. Vleugels endorsed this strategy. In addition, because the best available data suggest that 18%-32% of patients with dermatomyositis – whether classic or clinically amyopathic – have or will develop internal malignancy, she and her Boston colleagues routinely obtain CT scans of the chest, abdomen, and pelvis in all patients diagnosed with dermatomyositis. Women with dermatomyositis also undergo transvaginal pelvic ultrasound, which is a better screening tool for ovarian cancer. These studies are supplemented by age-appropriate GI endoscopy and stool occult blood tests. Women also get Pap smears and CA 125 measurement.

The cancer risk is greatest in the first 3 years following diagnosis of dermatomyositis, and remains high for at least 5 years.

The best data on the incidence of dermatomyositis in the United States, according to Dr. Vleugels, come from a population-based Mayo Clinic study conducted in Olmsted County, Minn. The overall incidence of dermatomyositis was 9.63 cases per 1 million population, with 21% of affected individuals having clinically amyopathic dermatomyositis. The internal malignancy rate wasn’t significantly different between patients with classic and clinically amyopathic dermatomyositis (Arch. Dermatol. 2010;146:26-30).

Dr. Vleugels reported having no financial conflicts.

SNOWMASS, COLO. – Serial pulmonary function testing, including diffusion capacity, is routinely warranted – but all too often overlooked – in patients with skin-predominant dermatomyositis.

It’s not widely appreciated that patients with clinically amyopathic dermatomyositis and those with classic dermatomyositis are at similarly high risk for developing interstitial lung disease, Dr. Ruth Ann Vleugels observed at a symposium sponsored by the American College of Rheumatology.

"I often see patients with clinically amyopathic dermatomyositis who are assumed to have skin-limited disease and have never had pulmonary function tests. All these patients really should have serial pulmonary function tests with diffusion capacity studies. This is probably what’s most often forgotten, particularly in the evaluation of our amyopathic patients," declared Dr. Vleugels, a dermatologist who is director of the connective tissue disease clinic at Brigham and Women’s Hospital in Boston and codirector of the rheumatology-dermatology clinic at Children’s Hospital Boston.

She added that patients with amyopathic dermatomyositis, like those with classic dermatomyositis, are also at elevated risk for internal malignancy.

"The take-home message is, clinically amyopathic patients can have cancer and interstitial lung disease. So even though they don’t have muscle disease, we need to screen identically for malignancy and also work them up for interstitial lung disease," the dermatologist continued.

Dr. Vleugels highlighted a retrospective study by investigators at the University of Pennsylvania in Philadelphia that underscored the similarly high risk of interstitial lung disease (ILD) in patients with skin-predominant and classic dermatomyositis.

The study involved 71 patients with dermatomyositis who were screened for ILD via thin-slice chest CT scans and pulmonary function testing that included diffusing capacity for carbon monoxide (DLCO). In all, 35 patients had clinically amyopathic dermatomyositis (a condition formerly known as dermatomyositis sine myositis) and 36 had the classic form of the disease featuring muscle involvement.

The overall prevalence of ILD by CT scan was 23%. The pulmonary disease was present in 10 of 35 patients with clinically amyopathic dermatomyositis and in 6 of 36 subjects with the classic form of dermatomyositis featuring muscle involvement, rates that were not significantly different (Arch. Dermatol. 2010;146:729-38).

All dermatomyositis patients with ILD had a reduced DLCO. In addition, 7 of 35 with clinically amyopathic dermatomyositis and 11 of 36 with classic dermatomyositis had a low DLCO in the absence of CT evidence of ILD. The clinical implication of such findings remains unclear. It may be that an isolated low DLCO with a normal chest CT is an indication of early ILD, or perhaps pulmonary hypertension, but a larger study with longer follow-up will be required to learn whether, in fact, an isolated low DLCO in the setting of dermatomyositis predicts progression to restrictive lung disease.

Because all patients in this study with CT evidence of ILD also had a low DLCO, the investigators recommended that all dermatomyositis patients routinely undergo serial screening with pulmonary function tests. Those with a moderate or severe reduction in DLCO (that is, less than 61% of the predicted value) should undergo thin-slice CT and referral to a pulmonologist for further management.

Dermatomyositis patients with a mildly low DLCO (defined as 61%-75% of predicted) should also have a high-resolution chest CT, as well as echocardiography to rule out pulmonary hypertension. If these studies prove negative, close follow-up with serial pulmonary function tests as well as inquiry regarding the clinical symptoms of shortness of breath and cough is appropriate, according to the Penn investigators.

Dr. Vleugels endorsed this strategy. In addition, because the best available data suggest that 18%-32% of patients with dermatomyositis – whether classic or clinically amyopathic – have or will develop internal malignancy, she and her Boston colleagues routinely obtain CT scans of the chest, abdomen, and pelvis in all patients diagnosed with dermatomyositis. Women with dermatomyositis also undergo transvaginal pelvic ultrasound, which is a better screening tool for ovarian cancer. These studies are supplemented by age-appropriate GI endoscopy and stool occult blood tests. Women also get Pap smears and CA 125 measurement.

The cancer risk is greatest in the first 3 years following diagnosis of dermatomyositis, and remains high for at least 5 years.

The best data on the incidence of dermatomyositis in the United States, according to Dr. Vleugels, come from a population-based Mayo Clinic study conducted in Olmsted County, Minn. The overall incidence of dermatomyositis was 9.63 cases per 1 million population, with 21% of affected individuals having clinically amyopathic dermatomyositis. The internal malignancy rate wasn’t significantly different between patients with classic and clinically amyopathic dermatomyositis (Arch. Dermatol. 2010;146:26-30).

Dr. Vleugels reported having no financial conflicts.

SNOWMASS, COLO. – Serial pulmonary function testing, including diffusion capacity, is routinely warranted – but all too often overlooked – in patients with skin-predominant dermatomyositis.

It’s not widely appreciated that patients with clinically amyopathic dermatomyositis and those with classic dermatomyositis are at similarly high risk for developing interstitial lung disease, Dr. Ruth Ann Vleugels observed at a symposium sponsored by the American College of Rheumatology.

"I often see patients with clinically amyopathic dermatomyositis who are assumed to have skin-limited disease and have never had pulmonary function tests. All these patients really should have serial pulmonary function tests with diffusion capacity studies. This is probably what’s most often forgotten, particularly in the evaluation of our amyopathic patients," declared Dr. Vleugels, a dermatologist who is director of the connective tissue disease clinic at Brigham and Women’s Hospital in Boston and codirector of the rheumatology-dermatology clinic at Children’s Hospital Boston.

She added that patients with amyopathic dermatomyositis, like those with classic dermatomyositis, are also at elevated risk for internal malignancy.

"The take-home message is, clinically amyopathic patients can have cancer and interstitial lung disease. So even though they don’t have muscle disease, we need to screen identically for malignancy and also work them up for interstitial lung disease," the dermatologist continued.

Dr. Vleugels highlighted a retrospective study by investigators at the University of Pennsylvania in Philadelphia that underscored the similarly high risk of interstitial lung disease (ILD) in patients with skin-predominant and classic dermatomyositis.

The study involved 71 patients with dermatomyositis who were screened for ILD via thin-slice chest CT scans and pulmonary function testing that included diffusing capacity for carbon monoxide (DLCO). In all, 35 patients had clinically amyopathic dermatomyositis (a condition formerly known as dermatomyositis sine myositis) and 36 had the classic form of the disease featuring muscle involvement.

The overall prevalence of ILD by CT scan was 23%. The pulmonary disease was present in 10 of 35 patients with clinically amyopathic dermatomyositis and in 6 of 36 subjects with the classic form of dermatomyositis featuring muscle involvement, rates that were not significantly different (Arch. Dermatol. 2010;146:729-38).

All dermatomyositis patients with ILD had a reduced DLCO. In addition, 7 of 35 with clinically amyopathic dermatomyositis and 11 of 36 with classic dermatomyositis had a low DLCO in the absence of CT evidence of ILD. The clinical implication of such findings remains unclear. It may be that an isolated low DLCO with a normal chest CT is an indication of early ILD, or perhaps pulmonary hypertension, but a larger study with longer follow-up will be required to learn whether, in fact, an isolated low DLCO in the setting of dermatomyositis predicts progression to restrictive lung disease.

Because all patients in this study with CT evidence of ILD also had a low DLCO, the investigators recommended that all dermatomyositis patients routinely undergo serial screening with pulmonary function tests. Those with a moderate or severe reduction in DLCO (that is, less than 61% of the predicted value) should undergo thin-slice CT and referral to a pulmonologist for further management.

Dermatomyositis patients with a mildly low DLCO (defined as 61%-75% of predicted) should also have a high-resolution chest CT, as well as echocardiography to rule out pulmonary hypertension. If these studies prove negative, close follow-up with serial pulmonary function tests as well as inquiry regarding the clinical symptoms of shortness of breath and cough is appropriate, according to the Penn investigators.

Dr. Vleugels endorsed this strategy. In addition, because the best available data suggest that 18%-32% of patients with dermatomyositis – whether classic or clinically amyopathic – have or will develop internal malignancy, she and her Boston colleagues routinely obtain CT scans of the chest, abdomen, and pelvis in all patients diagnosed with dermatomyositis. Women with dermatomyositis also undergo transvaginal pelvic ultrasound, which is a better screening tool for ovarian cancer. These studies are supplemented by age-appropriate GI endoscopy and stool occult blood tests. Women also get Pap smears and CA 125 measurement.

The cancer risk is greatest in the first 3 years following diagnosis of dermatomyositis, and remains high for at least 5 years.

The best data on the incidence of dermatomyositis in the United States, according to Dr. Vleugels, come from a population-based Mayo Clinic study conducted in Olmsted County, Minn. The overall incidence of dermatomyositis was 9.63 cases per 1 million population, with 21% of affected individuals having clinically amyopathic dermatomyositis. The internal malignancy rate wasn’t significantly different between patients with classic and clinically amyopathic dermatomyositis (Arch. Dermatol. 2010;146:26-30).

Dr. Vleugels reported having no financial conflicts.

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

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

Here’s why:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Here’s why:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Here’s why:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

WAIKOLOA, HAWAII – New acne management recommendations from the American Acne and Rosacea Society are the first guidelines to specifically address pediatric acne.

"Acne is a common problem, and the presentations and differential diagnosis differ among the various ages of childhood and adolescence. We had a strong desire to increase recognition and improve management of pediatric and adolescent acne across the spectrum of primary and specialty care," explained Dr. Lawrence F. Eichenfield, cochair of the guideline-writing panel comprised of general pediatricians, pediatric dermatologists, and acne experts.

The comprehensive guidelines provide a simple and efficient classification scheme in which acne is categorized as comedonal, inflammatory/mixed, or nodular, and graded as globally mild, moderate, or severe. The guidelines offer detailed algorithms for the treatment of each category.

The treatment algorithms are flexible, with multiple options available based upon considerations including financial cost and treatment history.

Regimen complexity is another major consideration. Treatment adherence in pediatric and adolescent acne patients is notoriously a much bigger problem than in adults. Simple, once-daily combination products addressing multiple acne pathogenic mechanisms are advantageous.

Adolescent Acne

The treatment algorithm for the adolescent with mild comedonal or inflammatory/mixed lesions begins with two broad options for initial therapy. Both are topical regimens. The first consists of monotherapy with benzoyl peroxide or a topical retinoid, which can be an inexpensive option. The second is topical fixed-dose combination therapy, which can cost far more but achieves faster clearance, Dr. Eichenfield said at the seminar sponsored by Skin Disease Education Foundation (SDEF). Recommended combinations include benzoyl peroxide with a topical antibiotic or retinoid.

Alternatively, the panel noted that topical dapsone can be used either as initial monotherapy or in place of a topical antibiotic. The panel was in agreement that a topical antibiotic should only be prescribed in conjunction with benzoyl peroxide in order to help prevent the emergence of bacterial resistance, he said.

Doxycycline and other oral antibiotics are to be reserved for treatment of moderate to severe acne, and their use should be limited to 3-6 months, according to the guidelines.

"An oral antibiotic alone is substandard care now. It needs to be accompanied by a topical retinoid, a retinoid/benzoyl peroxide, or retinoid/topical antibiotic combination to minimize resistance," Dr. Eichenfield said.

The guidelines note that it is appropriate for primary care physicians to immediately refer an adolescent who presents with severe acne to a dermatologist. Many such patients will be best-treated with oral isotretinoin, he noted.

Preadolescent Acne

Preadolescent acne arising in children aged 7-12 is common and considered normal. It typically begins with comedones over the forehead and midface, with truncal lesions being far less common.

Treatment follows the same algorithms as adolescent acne, with the caveat that most preadolescent therapy is off-label, since, until quite recently, nearly all treatment studies were restricted to patients aged 12 years and older. Therefore, in formulating a treatment strategy for preadolescents, the panel had to shift gears and switch from the evidence-based approach emphasized elsewhere in the guidelines to expert consensus, said Dr. Eichenfield, professor of clinical pediatrics and dermatology at the University of California, San Diego.

Infantile Acne

Infantile acne generally doesn’t show up until after the first several months of life. It is comedonal, although papules, pustules, nodules, and cysts may also be present. Infantile acne can do significant lasting damage, and treatment is warranted.

Neonatal Acne

Acne developing within the first 6 weeks after birth is classified as neonatal acne. However, the erythematous papules and pustules located on the face, neck, scalp, and torso are not true acne. The skin lesions, also known as neonatal cephalic pustulosis, are associated with skin colonization by Malassezia globosa and M. sympodialis. It is a self-limited condition, although it may clear faster if treated using topical ketoconazole cream or another anti-yeast medication.

Among the other issues addressed in the report are diet and acne, the appropriate use of the various classes of medications, when and how to use oral contraceptive pills for acne, the important distinction between neonatal and infantile acne, how to prescribe the big gun – isotretinoin – in young patients, and when to refer a child with acne for a endocrinology workup, said Dr. Eichenfield.

He explained that acne arising in mid-childhood – age 1-7 years – is a red flag for an increased risk of an endocrinologic disorder. Referral to a pediatric endocrinologist is warranted if a child displays any abnormalities in height and growth, blood pressure, or displays signs of early sexual maturation. Dr. Eichenfield picks up the phone personally, he said, to talk to the pediatric endocrinologist, and to make sure the child won’t wait long for an endocrinologic evaluation.

Publication of the guidelines is pending, he noted. In the meantime, physicians can obtain an introduction to the guidelines, including full details of the treatment algorithms, while earning 1 hour of CME credit by viewing a 56-minute video featuring Dr. Eichenfield and other guideline panelists at www.acneandrosacea.org.

The acne guidelines project was supported by the American Acne and Rosacea Society.

Dr. Eichenfield reported receiving research support or serving as a consultant to Galderma, Johnson & Johnson, Medicis, Stiefel, Valeant, and Ortho-McNeil (Jansen Pharmaceuticals).

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – New acne management recommendations from the American Acne and Rosacea Society are the first guidelines to specifically address pediatric acne.

"Acne is a common problem, and the presentations and differential diagnosis differ among the various ages of childhood and adolescence. We had a strong desire to increase recognition and improve management of pediatric and adolescent acne across the spectrum of primary and specialty care," explained Dr. Lawrence F. Eichenfield, cochair of the guideline-writing panel comprised of general pediatricians, pediatric dermatologists, and acne experts.

The comprehensive guidelines provide a simple and efficient classification scheme in which acne is categorized as comedonal, inflammatory/mixed, or nodular, and graded as globally mild, moderate, or severe. The guidelines offer detailed algorithms for the treatment of each category.

The treatment algorithms are flexible, with multiple options available based upon considerations including financial cost and treatment history.

Regimen complexity is another major consideration. Treatment adherence in pediatric and adolescent acne patients is notoriously a much bigger problem than in adults. Simple, once-daily combination products addressing multiple acne pathogenic mechanisms are advantageous.

Adolescent Acne

The treatment algorithm for the adolescent with mild comedonal or inflammatory/mixed lesions begins with two broad options for initial therapy. Both are topical regimens. The first consists of monotherapy with benzoyl peroxide or a topical retinoid, which can be an inexpensive option. The second is topical fixed-dose combination therapy, which can cost far more but achieves faster clearance, Dr. Eichenfield said at the seminar sponsored by Skin Disease Education Foundation (SDEF). Recommended combinations include benzoyl peroxide with a topical antibiotic or retinoid.

Alternatively, the panel noted that topical dapsone can be used either as initial monotherapy or in place of a topical antibiotic. The panel was in agreement that a topical antibiotic should only be prescribed in conjunction with benzoyl peroxide in order to help prevent the emergence of bacterial resistance, he said.

Doxycycline and other oral antibiotics are to be reserved for treatment of moderate to severe acne, and their use should be limited to 3-6 months, according to the guidelines.

"An oral antibiotic alone is substandard care now. It needs to be accompanied by a topical retinoid, a retinoid/benzoyl peroxide, or retinoid/topical antibiotic combination to minimize resistance," Dr. Eichenfield said.

The guidelines note that it is appropriate for primary care physicians to immediately refer an adolescent who presents with severe acne to a dermatologist. Many such patients will be best-treated with oral isotretinoin, he noted.

Preadolescent Acne

Preadolescent acne arising in children aged 7-12 is common and considered normal. It typically begins with comedones over the forehead and midface, with truncal lesions being far less common.

Treatment follows the same algorithms as adolescent acne, with the caveat that most preadolescent therapy is off-label, since, until quite recently, nearly all treatment studies were restricted to patients aged 12 years and older. Therefore, in formulating a treatment strategy for preadolescents, the panel had to shift gears and switch from the evidence-based approach emphasized elsewhere in the guidelines to expert consensus, said Dr. Eichenfield, professor of clinical pediatrics and dermatology at the University of California, San Diego.

Infantile Acne

Infantile acne generally doesn’t show up until after the first several months of life. It is comedonal, although papules, pustules, nodules, and cysts may also be present. Infantile acne can do significant lasting damage, and treatment is warranted.

Neonatal Acne

Acne developing within the first 6 weeks after birth is classified as neonatal acne. However, the erythematous papules and pustules located on the face, neck, scalp, and torso are not true acne. The skin lesions, also known as neonatal cephalic pustulosis, are associated with skin colonization by Malassezia globosa and M. sympodialis. It is a self-limited condition, although it may clear faster if treated using topical ketoconazole cream or another anti-yeast medication.

Among the other issues addressed in the report are diet and acne, the appropriate use of the various classes of medications, when and how to use oral contraceptive pills for acne, the important distinction between neonatal and infantile acne, how to prescribe the big gun – isotretinoin – in young patients, and when to refer a child with acne for a endocrinology workup, said Dr. Eichenfield.

He explained that acne arising in mid-childhood – age 1-7 years – is a red flag for an increased risk of an endocrinologic disorder. Referral to a pediatric endocrinologist is warranted if a child displays any abnormalities in height and growth, blood pressure, or displays signs of early sexual maturation. Dr. Eichenfield picks up the phone personally, he said, to talk to the pediatric endocrinologist, and to make sure the child won’t wait long for an endocrinologic evaluation.

Publication of the guidelines is pending, he noted. In the meantime, physicians can obtain an introduction to the guidelines, including full details of the treatment algorithms, while earning 1 hour of CME credit by viewing a 56-minute video featuring Dr. Eichenfield and other guideline panelists at www.acneandrosacea.org.

The acne guidelines project was supported by the American Acne and Rosacea Society.

Dr. Eichenfield reported receiving research support or serving as a consultant to Galderma, Johnson & Johnson, Medicis, Stiefel, Valeant, and Ortho-McNeil (Jansen Pharmaceuticals).

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – New acne management recommendations from the American Acne and Rosacea Society are the first guidelines to specifically address pediatric acne.

"Acne is a common problem, and the presentations and differential diagnosis differ among the various ages of childhood and adolescence. We had a strong desire to increase recognition and improve management of pediatric and adolescent acne across the spectrum of primary and specialty care," explained Dr. Lawrence F. Eichenfield, cochair of the guideline-writing panel comprised of general pediatricians, pediatric dermatologists, and acne experts.

The comprehensive guidelines provide a simple and efficient classification scheme in which acne is categorized as comedonal, inflammatory/mixed, or nodular, and graded as globally mild, moderate, or severe. The guidelines offer detailed algorithms for the treatment of each category.

The treatment algorithms are flexible, with multiple options available based upon considerations including financial cost and treatment history.

Regimen complexity is another major consideration. Treatment adherence in pediatric and adolescent acne patients is notoriously a much bigger problem than in adults. Simple, once-daily combination products addressing multiple acne pathogenic mechanisms are advantageous.

Adolescent Acne

The treatment algorithm for the adolescent with mild comedonal or inflammatory/mixed lesions begins with two broad options for initial therapy. Both are topical regimens. The first consists of monotherapy with benzoyl peroxide or a topical retinoid, which can be an inexpensive option. The second is topical fixed-dose combination therapy, which can cost far more but achieves faster clearance, Dr. Eichenfield said at the seminar sponsored by Skin Disease Education Foundation (SDEF). Recommended combinations include benzoyl peroxide with a topical antibiotic or retinoid.

Alternatively, the panel noted that topical dapsone can be used either as initial monotherapy or in place of a topical antibiotic. The panel was in agreement that a topical antibiotic should only be prescribed in conjunction with benzoyl peroxide in order to help prevent the emergence of bacterial resistance, he said.

Doxycycline and other oral antibiotics are to be reserved for treatment of moderate to severe acne, and their use should be limited to 3-6 months, according to the guidelines.

"An oral antibiotic alone is substandard care now. It needs to be accompanied by a topical retinoid, a retinoid/benzoyl peroxide, or retinoid/topical antibiotic combination to minimize resistance," Dr. Eichenfield said.

The guidelines note that it is appropriate for primary care physicians to immediately refer an adolescent who presents with severe acne to a dermatologist. Many such patients will be best-treated with oral isotretinoin, he noted.

Preadolescent Acne

Preadolescent acne arising in children aged 7-12 is common and considered normal. It typically begins with comedones over the forehead and midface, with truncal lesions being far less common.

Treatment follows the same algorithms as adolescent acne, with the caveat that most preadolescent therapy is off-label, since, until quite recently, nearly all treatment studies were restricted to patients aged 12 years and older. Therefore, in formulating a treatment strategy for preadolescents, the panel had to shift gears and switch from the evidence-based approach emphasized elsewhere in the guidelines to expert consensus, said Dr. Eichenfield, professor of clinical pediatrics and dermatology at the University of California, San Diego.

Infantile Acne

Infantile acne generally doesn’t show up until after the first several months of life. It is comedonal, although papules, pustules, nodules, and cysts may also be present. Infantile acne can do significant lasting damage, and treatment is warranted.

Neonatal Acne

Acne developing within the first 6 weeks after birth is classified as neonatal acne. However, the erythematous papules and pustules located on the face, neck, scalp, and torso are not true acne. The skin lesions, also known as neonatal cephalic pustulosis, are associated with skin colonization by Malassezia globosa and M. sympodialis. It is a self-limited condition, although it may clear faster if treated using topical ketoconazole cream or another anti-yeast medication.

Among the other issues addressed in the report are diet and acne, the appropriate use of the various classes of medications, when and how to use oral contraceptive pills for acne, the important distinction between neonatal and infantile acne, how to prescribe the big gun – isotretinoin – in young patients, and when to refer a child with acne for a endocrinology workup, said Dr. Eichenfield.

He explained that acne arising in mid-childhood – age 1-7 years – is a red flag for an increased risk of an endocrinologic disorder. Referral to a pediatric endocrinologist is warranted if a child displays any abnormalities in height and growth, blood pressure, or displays signs of early sexual maturation. Dr. Eichenfield picks up the phone personally, he said, to talk to the pediatric endocrinologist, and to make sure the child won’t wait long for an endocrinologic evaluation.

Publication of the guidelines is pending, he noted. In the meantime, physicians can obtain an introduction to the guidelines, including full details of the treatment algorithms, while earning 1 hour of CME credit by viewing a 56-minute video featuring Dr. Eichenfield and other guideline panelists at www.acneandrosacea.org.

The acne guidelines project was supported by the American Acne and Rosacea Society.

Dr. Eichenfield reported receiving research support or serving as a consultant to Galderma, Johnson & Johnson, Medicis, Stiefel, Valeant, and Ortho-McNeil (Jansen Pharmaceuticals).

SDEF and this news organization are owned by Elsevier.