ACR Winter Rheumatology Symposium 2012

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.

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SNOWMASS, COLO. – The guideline-endorsed demotion of nonsteroidal anti-inflammatory drugs in favor of narcotic analgesics for chronic pain has led to a marked increase in falls, fractures, and other bad outcomes among elderly arthritis patients.

"I think the real take-home message here is that current guidelines for the treatment of pain should be revisited," Dr. Bruce N. Cronstein asserted at a symposium sponsored by the American College of Rheumatology.

Since the cyclo-oxygenase-2 (COX-2)-selective NSAID rofecoxib (Vioxx) was famously taken off the market in late 2004 because of a scandal related to cover-up of an increased risk of myocardial infarction (MI), prescriptions for narcotic analgesics in elderly patients with arthritis have risen sharply. This trend accelerated after the 2007 publication of an American Heart Association (AHA) scientific statement on the treatment of chronic pain in patients with or at increased risk for heart disease (Circulation 2007;115:1634-42). The AHA guidelines elevated short-term use of narcotic analgesics to first-tier status alongside aspirin, acetaminophen, and tramadol, while demoting both COX-2-selective and nonselective NSAIDs to second-tier status.

The AHA recommendations have been embraced by geriatrics groups and other medical societies. Notably, however, the American College of Rheumatology has declined to get on board, observed Dr. Cronstein, Dr. Paul R. Esserman professor of medicine at New York University.

The AHA guidelines, in his view, are poorly done. The problem is one of tunnel vision. The guidelines focus on the evidence of increased cardiovascular risk associated with nearly all NSAIDs without considering how the drugs stack up in terms of overall safety – noncardiovascular as well as cardiovascular – compared with the other major analgesic group: narcotic analgesics. And it turns out that the NSAIDs look pretty good in comparison, the rheumatologist added.

"You’re trading off falls and fractures for MIs – and it turns out that in patients over age 65, the mortality from hip fracture is significantly greater than it is for MI," said Dr. Cronstein, who is also director of the Clinical and Translational Science Institute, which is a partnership between New York University and the New York City Health and Hospitals Corporation.

Dr. Cronstein cited a large Medicare study conducted by investigators at Brigham and Women’s Hospital, Boston. They examined the comparative safety of analgesics in elderly arthritis patients and concluded that narcotic analgesics come up short.

The investigators sifted through the population of Medicare beneficiaries in Pennsylvania and New Jersey to identify elderly patients with rheumatoid arthritis or osteoarthritis (OA) who were started on a nonselective NSAID, a COX-2-selective NSAID, or a narcotic analgesic during 1999-2005. They came up with 4,280 propensity score–matched patients in each of the three groups. The subjects’ mean age was 80 years, and 85% were women. Patients with prior cancer or nursing-home use were excluded from the study in order to avoid data skewing.

The composite incidence of fractures of the hip, pelvis, humerus, or radius in this National Institutes of Health–funded study was 26 per 1,000 person-years among patients on nonselective NSAIDs, 19 with COX-2-selective NSAIDs, and 101 with opioids.

While it’s not really surprising that opiate analgesics should be associated with increased risk of falls and fractures, another finding in this study proved unexpected: Intriguingly, the composite cardiovascular event rate was 77 per 1,000 person-years with nonselective NSAIDs, 88 per 1,000 with COX-2-selective NSAIDs, and 122 in the narcotic analgesics group.

The patients taking opioids had a 77% greater risk of cardiovascular events and those taking COX-2-selective NSAIDs had a 28% greater risk than did patients on nonselective NSAIDs, according to findings from a multivariate Cox regression analysis. The fracture risk was 4.47-fold greater with narcotic analgesics than with NSAIDs. The gastrointestinal bleeding risk was 40% lower in the COX-2-selective NSAID group than in the other two study arms. The all-cause mortality risk was 87% greater in the narcotic analgesic group than with nonselective NSAIDs, while COX-2-selective NSAIDs were not associated with increased risk (Arch. Intern. Med. 2010; 170: 1968-76).

Dr. Cronstein also presented highlights of a not-yet-published study that documented the changing pattern of analgesic prescriptions for elderly patients with OA since 2005. He conducted the study with coinvestigators at the Geisinger Health Plan in Danville, Pa.

During 2001-2004, 24% of elderly patients with OA in the Geisinger system were on a narcotic-only for pain relief, 15% were on a narcotic analgesic plus a COX-2-selective NSAID, and 13% were on COX-2-selective NSAID monotherapy. But in 2005-2009, 56% of patients were on monotherapy with a narcotic analgesic, 9% were on a narcotic plus a COX-2-selective NSAID, and 2% were on COX-2-selective NSAID monotherapy.

Thus, the use of narcotic analgesics as the sole prescription medication for pain relief in elderly OA patients more than doubled after Vioxx was withdrawn from the market. The patients on narcotic analgesics with or without a COX-2-selective NSAID had a fourfold greater rate of falls or fractures than those on nonselective NSAIDs or COX-2-selective agents.

Dr. Cronstein and his coworkers also conducted a nested case-control study of 3,830 elderly Geisinger OA patients with fractures and 11,490 others matched for age and Charlson Comorbidity Index without fractures. In a multivariate analysis, patients on narcotic analgesics had a threefold greater risk of falls or fractures than those on either COX-2-selective or nonselective NSAIDs.

Dr. Cronstein observed that large studies indicate that the frequency of positive tests for prescription narcotic analgesics in employees involved in workplace accidents has increased significantly since 2005. Meanwhile, prescription narcotic analgesic abuse among younger individuals has ballooned. But while it’s interesting to speculate that these trends might be related to Vioxx going off the market and the general disenchantment with all NSAIDs that followed, there is no concrete evidence of such an association, he conceded.

This work was funded by the National Institutes of Health, the Geisinger Clinic, and the Clinical and Translational Science Institute. Dr. Cronstein reported that he has served as a paid consultant to Allos, Bristol-Myers Squibb, CanFite Biopharmaceuticals, Cypress Laboratories, Gismo Therapeutics, Novartis, Protalex, Regeneron, and Savient. He has received research grants from the National Institutes of Health and numerous pharmaceutical companies.

SNOWMASS, COLO. – The guideline-endorsed demotion of nonsteroidal anti-inflammatory drugs in favor of narcotic analgesics for chronic pain has led to a marked increase in falls, fractures, and other bad outcomes among elderly arthritis patients.

"I think the real take-home message here is that current guidelines for the treatment of pain should be revisited," Dr. Bruce N. Cronstein asserted at a symposium sponsored by the American College of Rheumatology.

Since the cyclo-oxygenase-2 (COX-2)-selective NSAID rofecoxib (Vioxx) was famously taken off the market in late 2004 because of a scandal related to cover-up of an increased risk of myocardial infarction (MI), prescriptions for narcotic analgesics in elderly patients with arthritis have risen sharply. This trend accelerated after the 2007 publication of an American Heart Association (AHA) scientific statement on the treatment of chronic pain in patients with or at increased risk for heart disease (Circulation 2007;115:1634-42). The AHA guidelines elevated short-term use of narcotic analgesics to first-tier status alongside aspirin, acetaminophen, and tramadol, while demoting both COX-2-selective and nonselective NSAIDs to second-tier status.

The AHA recommendations have been embraced by geriatrics groups and other medical societies. Notably, however, the American College of Rheumatology has declined to get on board, observed Dr. Cronstein, Dr. Paul R. Esserman professor of medicine at New York University.

The AHA guidelines, in his view, are poorly done. The problem is one of tunnel vision. The guidelines focus on the evidence of increased cardiovascular risk associated with nearly all NSAIDs without considering how the drugs stack up in terms of overall safety – noncardiovascular as well as cardiovascular – compared with the other major analgesic group: narcotic analgesics. And it turns out that the NSAIDs look pretty good in comparison, the rheumatologist added.

"You’re trading off falls and fractures for MIs – and it turns out that in patients over age 65, the mortality from hip fracture is significantly greater than it is for MI," said Dr. Cronstein, who is also director of the Clinical and Translational Science Institute, which is a partnership between New York University and the New York City Health and Hospitals Corporation.

Dr. Cronstein cited a large Medicare study conducted by investigators at Brigham and Women’s Hospital, Boston. They examined the comparative safety of analgesics in elderly arthritis patients and concluded that narcotic analgesics come up short.

The investigators sifted through the population of Medicare beneficiaries in Pennsylvania and New Jersey to identify elderly patients with rheumatoid arthritis or osteoarthritis (OA) who were started on a nonselective NSAID, a COX-2-selective NSAID, or a narcotic analgesic during 1999-2005. They came up with 4,280 propensity score–matched patients in each of the three groups. The subjects’ mean age was 80 years, and 85% were women. Patients with prior cancer or nursing-home use were excluded from the study in order to avoid data skewing.

The composite incidence of fractures of the hip, pelvis, humerus, or radius in this National Institutes of Health–funded study was 26 per 1,000 person-years among patients on nonselective NSAIDs, 19 with COX-2-selective NSAIDs, and 101 with opioids.

While it’s not really surprising that opiate analgesics should be associated with increased risk of falls and fractures, another finding in this study proved unexpected: Intriguingly, the composite cardiovascular event rate was 77 per 1,000 person-years with nonselective NSAIDs, 88 per 1,000 with COX-2-selective NSAIDs, and 122 in the narcotic analgesics group.

The patients taking opioids had a 77% greater risk of cardiovascular events and those taking COX-2-selective NSAIDs had a 28% greater risk than did patients on nonselective NSAIDs, according to findings from a multivariate Cox regression analysis. The fracture risk was 4.47-fold greater with narcotic analgesics than with NSAIDs. The gastrointestinal bleeding risk was 40% lower in the COX-2-selective NSAID group than in the other two study arms. The all-cause mortality risk was 87% greater in the narcotic analgesic group than with nonselective NSAIDs, while COX-2-selective NSAIDs were not associated with increased risk (Arch. Intern. Med. 2010; 170: 1968-76).

Dr. Cronstein also presented highlights of a not-yet-published study that documented the changing pattern of analgesic prescriptions for elderly patients with OA since 2005. He conducted the study with coinvestigators at the Geisinger Health Plan in Danville, Pa.

During 2001-2004, 24% of elderly patients with OA in the Geisinger system were on a narcotic-only for pain relief, 15% were on a narcotic analgesic plus a COX-2-selective NSAID, and 13% were on COX-2-selective NSAID monotherapy. But in 2005-2009, 56% of patients were on monotherapy with a narcotic analgesic, 9% were on a narcotic plus a COX-2-selective NSAID, and 2% were on COX-2-selective NSAID monotherapy.

Thus, the use of narcotic analgesics as the sole prescription medication for pain relief in elderly OA patients more than doubled after Vioxx was withdrawn from the market. The patients on narcotic analgesics with or without a COX-2-selective NSAID had a fourfold greater rate of falls or fractures than those on nonselective NSAIDs or COX-2-selective agents.

Dr. Cronstein and his coworkers also conducted a nested case-control study of 3,830 elderly Geisinger OA patients with fractures and 11,490 others matched for age and Charlson Comorbidity Index without fractures. In a multivariate analysis, patients on narcotic analgesics had a threefold greater risk of falls or fractures than those on either COX-2-selective or nonselective NSAIDs.

Dr. Cronstein observed that large studies indicate that the frequency of positive tests for prescription narcotic analgesics in employees involved in workplace accidents has increased significantly since 2005. Meanwhile, prescription narcotic analgesic abuse among younger individuals has ballooned. But while it’s interesting to speculate that these trends might be related to Vioxx going off the market and the general disenchantment with all NSAIDs that followed, there is no concrete evidence of such an association, he conceded.

This work was funded by the National Institutes of Health, the Geisinger Clinic, and the Clinical and Translational Science Institute. Dr. Cronstein reported that he has served as a paid consultant to Allos, Bristol-Myers Squibb, CanFite Biopharmaceuticals, Cypress Laboratories, Gismo Therapeutics, Novartis, Protalex, Regeneron, and Savient. He has received research grants from the National Institutes of Health and numerous pharmaceutical companies.

SNOWMASS, COLO. – The guideline-endorsed demotion of nonsteroidal anti-inflammatory drugs in favor of narcotic analgesics for chronic pain has led to a marked increase in falls, fractures, and other bad outcomes among elderly arthritis patients.

"I think the real take-home message here is that current guidelines for the treatment of pain should be revisited," Dr. Bruce N. Cronstein asserted at a symposium sponsored by the American College of Rheumatology.

Since the cyclo-oxygenase-2 (COX-2)-selective NSAID rofecoxib (Vioxx) was famously taken off the market in late 2004 because of a scandal related to cover-up of an increased risk of myocardial infarction (MI), prescriptions for narcotic analgesics in elderly patients with arthritis have risen sharply. This trend accelerated after the 2007 publication of an American Heart Association (AHA) scientific statement on the treatment of chronic pain in patients with or at increased risk for heart disease (Circulation 2007;115:1634-42). The AHA guidelines elevated short-term use of narcotic analgesics to first-tier status alongside aspirin, acetaminophen, and tramadol, while demoting both COX-2-selective and nonselective NSAIDs to second-tier status.

The AHA recommendations have been embraced by geriatrics groups and other medical societies. Notably, however, the American College of Rheumatology has declined to get on board, observed Dr. Cronstein, Dr. Paul R. Esserman professor of medicine at New York University.

The AHA guidelines, in his view, are poorly done. The problem is one of tunnel vision. The guidelines focus on the evidence of increased cardiovascular risk associated with nearly all NSAIDs without considering how the drugs stack up in terms of overall safety – noncardiovascular as well as cardiovascular – compared with the other major analgesic group: narcotic analgesics. And it turns out that the NSAIDs look pretty good in comparison, the rheumatologist added.

"You’re trading off falls and fractures for MIs – and it turns out that in patients over age 65, the mortality from hip fracture is significantly greater than it is for MI," said Dr. Cronstein, who is also director of the Clinical and Translational Science Institute, which is a partnership between New York University and the New York City Health and Hospitals Corporation.

Dr. Cronstein cited a large Medicare study conducted by investigators at Brigham and Women’s Hospital, Boston. They examined the comparative safety of analgesics in elderly arthritis patients and concluded that narcotic analgesics come up short.

The investigators sifted through the population of Medicare beneficiaries in Pennsylvania and New Jersey to identify elderly patients with rheumatoid arthritis or osteoarthritis (OA) who were started on a nonselective NSAID, a COX-2-selective NSAID, or a narcotic analgesic during 1999-2005. They came up with 4,280 propensity score–matched patients in each of the three groups. The subjects’ mean age was 80 years, and 85% were women. Patients with prior cancer or nursing-home use were excluded from the study in order to avoid data skewing.

The composite incidence of fractures of the hip, pelvis, humerus, or radius in this National Institutes of Health–funded study was 26 per 1,000 person-years among patients on nonselective NSAIDs, 19 with COX-2-selective NSAIDs, and 101 with opioids.

While it’s not really surprising that opiate analgesics should be associated with increased risk of falls and fractures, another finding in this study proved unexpected: Intriguingly, the composite cardiovascular event rate was 77 per 1,000 person-years with nonselective NSAIDs, 88 per 1,000 with COX-2-selective NSAIDs, and 122 in the narcotic analgesics group.

The patients taking opioids had a 77% greater risk of cardiovascular events and those taking COX-2-selective NSAIDs had a 28% greater risk than did patients on nonselective NSAIDs, according to findings from a multivariate Cox regression analysis. The fracture risk was 4.47-fold greater with narcotic analgesics than with NSAIDs. The gastrointestinal bleeding risk was 40% lower in the COX-2-selective NSAID group than in the other two study arms. The all-cause mortality risk was 87% greater in the narcotic analgesic group than with nonselective NSAIDs, while COX-2-selective NSAIDs were not associated with increased risk (Arch. Intern. Med. 2010; 170: 1968-76).

Dr. Cronstein also presented highlights of a not-yet-published study that documented the changing pattern of analgesic prescriptions for elderly patients with OA since 2005. He conducted the study with coinvestigators at the Geisinger Health Plan in Danville, Pa.

During 2001-2004, 24% of elderly patients with OA in the Geisinger system were on a narcotic-only for pain relief, 15% were on a narcotic analgesic plus a COX-2-selective NSAID, and 13% were on COX-2-selective NSAID monotherapy. But in 2005-2009, 56% of patients were on monotherapy with a narcotic analgesic, 9% were on a narcotic plus a COX-2-selective NSAID, and 2% were on COX-2-selective NSAID monotherapy.

Thus, the use of narcotic analgesics as the sole prescription medication for pain relief in elderly OA patients more than doubled after Vioxx was withdrawn from the market. The patients on narcotic analgesics with or without a COX-2-selective NSAID had a fourfold greater rate of falls or fractures than those on nonselective NSAIDs or COX-2-selective agents.

Dr. Cronstein and his coworkers also conducted a nested case-control study of 3,830 elderly Geisinger OA patients with fractures and 11,490 others matched for age and Charlson Comorbidity Index without fractures. In a multivariate analysis, patients on narcotic analgesics had a threefold greater risk of falls or fractures than those on either COX-2-selective or nonselective NSAIDs.

Dr. Cronstein observed that large studies indicate that the frequency of positive tests for prescription narcotic analgesics in employees involved in workplace accidents has increased significantly since 2005. Meanwhile, prescription narcotic analgesic abuse among younger individuals has ballooned. But while it’s interesting to speculate that these trends might be related to Vioxx going off the market and the general disenchantment with all NSAIDs that followed, there is no concrete evidence of such an association, he conceded.

This work was funded by the National Institutes of Health, the Geisinger Clinic, and the Clinical and Translational Science Institute. Dr. Cronstein reported that he has served as a paid consultant to Allos, Bristol-Myers Squibb, CanFite Biopharmaceuticals, Cypress Laboratories, Gismo Therapeutics, Novartis, Protalex, Regeneron, and Savient. He has received research grants from the National Institutes of Health and numerous pharmaceutical companies.

SNOWMASS, COLO. – Unless you’re a dermatologist, you’re likely to need just three topical corticosteroids from the dizzying array of available products.

That’s the contention of Dr. Ruth Ann 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 advises gaining familiarity with the use of desonide, triamcinolone 0.1%, and clobetasol.

"Honestly, this is 90% of what I use. If you have a ‘favorites’ tab on your [electronic health record system] you can plug in these three with their instructions and you’ll never need to use any other topical steroids," she said at the conference.

Clobetasol is a potent steroid, triamcinolone 0.1% is midstrength, and desonide is lower-potency. Clobetasol and triamcinolone 0.1% are generally utilized for skin disease on the body, whereas desonide is the appropriate choice for skin disorders on the face, groin, axillae, and breasts.

Many nondermatologists are leery about long-term topical corticosteroid therapy. But there’s no need for concern as long as the drugs are used with breaks, Dr. Vleugels emphasized.

"You can use topical steroids for life with no issues; we know that from studies in our psoriasis and eczema patients. But we can’t use them without breaks. That’s the most important message in counseling your patients. For the body, it’s 2 weeks on, 1 week off. For the face, it’s 1 week on, 1 week off. If they do that, you won’t see steroid side effects," she said.

The side effects that are seen with uninterrupted topical steroid therapy include skin atrophy, striae, lightening, and telangiectasias.

When desonide is used in treating the groin, breasts, or armpits, the schedule is 1 week on, 1 week off – the same as the facial schedule.

Dr. Vleugels makes an exception to these rules when she’s treating facial lesions related to autoimmune diseases. Because she wants to get rapid clearing, she often turns to a burst of clobetasol in these circumstances. The schedule is 1 week on, 1 week off.

"A typical situation might be when a rheumatologist calls me and says, ‘I have a patient who got a horrible photosensitive malar rash while outdoors last weekend, and she’s already on maximum-dose systemic therapy.’ I’d say, just give her 1 week of clobetasol on her face; she’ll be better in 3-4 days. But you need to carefully tell your patients that if they’re going to put it on their face they have to follow the rule for face disease: 1 week on, 1 week off," she said.

Cream or ointment? For most patients with autoimmune diseases, pick a topical steroid cream; it’ll result in better compliance. A steroid ointment is preferable when skin hydration is a consideration, as in atopic dermatitis. Because ointments are effectively stronger and more deeply penetrating than creams, a steroid ointment is also the best choice in treating disease involving particularly thick skin, such as palmar or plantar psoriasis, where the medication is employed under occlusion with gloves or socks, Dr. Vleugels explained.

To avoid undertreatment, it’s important to specify on the prescription how much medication the pharmacy is to provide. A 60-g tube of a topical steroid won’t last longer than a week in a patient with a full-body skin eruption; Dr. Vleugels generally orders 120-240 g for such patients. For patients treating lesions on the face or other sensitive areas, she cuts the prescription to 30 g with a single refill unless she’s comfortable with that individual’s adherence.

Topical calcineurin inhibitors have a limited role. Dr. Vleugels considers using 0.3% tacrolimus during patients’ week-long topical steroid breaks if their disease isn’t well controlled during those intervals. She also considers tacrolimus in patients with periorbital skin lesions, where steroid atrophy is a particular concern. Topical pimecrolimus is considerably less effective than tacrolimus, and she never uses pimecrolimus in adults.

"I use these agents much less frequently than topical steroids. They’re often low efficacy for the cost [compared with] a topical steroid, used safely," the dermatologist said.

She reported having no financial conflicts.

SNOWMASS, COLO. – Unless you’re a dermatologist, you’re likely to need just three topical corticosteroids from the dizzying array of available products.

That’s the contention of Dr. Ruth Ann 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 advises gaining familiarity with the use of desonide, triamcinolone 0.1%, and clobetasol.

"Honestly, this is 90% of what I use. If you have a ‘favorites’ tab on your [electronic health record system] you can plug in these three with their instructions and you’ll never need to use any other topical steroids," she said at the conference.

Clobetasol is a potent steroid, triamcinolone 0.1% is midstrength, and desonide is lower-potency. Clobetasol and triamcinolone 0.1% are generally utilized for skin disease on the body, whereas desonide is the appropriate choice for skin disorders on the face, groin, axillae, and breasts.

Many nondermatologists are leery about long-term topical corticosteroid therapy. But there’s no need for concern as long as the drugs are used with breaks, Dr. Vleugels emphasized.

"You can use topical steroids for life with no issues; we know that from studies in our psoriasis and eczema patients. But we can’t use them without breaks. That’s the most important message in counseling your patients. For the body, it’s 2 weeks on, 1 week off. For the face, it’s 1 week on, 1 week off. If they do that, you won’t see steroid side effects," she said.

The side effects that are seen with uninterrupted topical steroid therapy include skin atrophy, striae, lightening, and telangiectasias.

When desonide is used in treating the groin, breasts, or armpits, the schedule is 1 week on, 1 week off – the same as the facial schedule.

Dr. Vleugels makes an exception to these rules when she’s treating facial lesions related to autoimmune diseases. Because she wants to get rapid clearing, she often turns to a burst of clobetasol in these circumstances. The schedule is 1 week on, 1 week off.

"A typical situation might be when a rheumatologist calls me and says, ‘I have a patient who got a horrible photosensitive malar rash while outdoors last weekend, and she’s already on maximum-dose systemic therapy.’ I’d say, just give her 1 week of clobetasol on her face; she’ll be better in 3-4 days. But you need to carefully tell your patients that if they’re going to put it on their face they have to follow the rule for face disease: 1 week on, 1 week off," she said.

Cream or ointment? For most patients with autoimmune diseases, pick a topical steroid cream; it’ll result in better compliance. A steroid ointment is preferable when skin hydration is a consideration, as in atopic dermatitis. Because ointments are effectively stronger and more deeply penetrating than creams, a steroid ointment is also the best choice in treating disease involving particularly thick skin, such as palmar or plantar psoriasis, where the medication is employed under occlusion with gloves or socks, Dr. Vleugels explained.

To avoid undertreatment, it’s important to specify on the prescription how much medication the pharmacy is to provide. A 60-g tube of a topical steroid won’t last longer than a week in a patient with a full-body skin eruption; Dr. Vleugels generally orders 120-240 g for such patients. For patients treating lesions on the face or other sensitive areas, she cuts the prescription to 30 g with a single refill unless she’s comfortable with that individual’s adherence.

Topical calcineurin inhibitors have a limited role. Dr. Vleugels considers using 0.3% tacrolimus during patients’ week-long topical steroid breaks if their disease isn’t well controlled during those intervals. She also considers tacrolimus in patients with periorbital skin lesions, where steroid atrophy is a particular concern. Topical pimecrolimus is considerably less effective than tacrolimus, and she never uses pimecrolimus in adults.

"I use these agents much less frequently than topical steroids. They’re often low efficacy for the cost [compared with] a topical steroid, used safely," the dermatologist said.

She reported having no financial conflicts.

SNOWMASS, COLO. – Unless you’re a dermatologist, you’re likely to need just three topical corticosteroids from the dizzying array of available products.

That’s the contention of Dr. Ruth Ann 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 advises gaining familiarity with the use of desonide, triamcinolone 0.1%, and clobetasol.

"Honestly, this is 90% of what I use. If you have a ‘favorites’ tab on your [electronic health record system] you can plug in these three with their instructions and you’ll never need to use any other topical steroids," she said at the conference.

Clobetasol is a potent steroid, triamcinolone 0.1% is midstrength, and desonide is lower-potency. Clobetasol and triamcinolone 0.1% are generally utilized for skin disease on the body, whereas desonide is the appropriate choice for skin disorders on the face, groin, axillae, and breasts.

Many nondermatologists are leery about long-term topical corticosteroid therapy. But there’s no need for concern as long as the drugs are used with breaks, Dr. Vleugels emphasized.

"You can use topical steroids for life with no issues; we know that from studies in our psoriasis and eczema patients. But we can’t use them without breaks. That’s the most important message in counseling your patients. For the body, it’s 2 weeks on, 1 week off. For the face, it’s 1 week on, 1 week off. If they do that, you won’t see steroid side effects," she said.

The side effects that are seen with uninterrupted topical steroid therapy include skin atrophy, striae, lightening, and telangiectasias.

When desonide is used in treating the groin, breasts, or armpits, the schedule is 1 week on, 1 week off – the same as the facial schedule.

Dr. Vleugels makes an exception to these rules when she’s treating facial lesions related to autoimmune diseases. Because she wants to get rapid clearing, she often turns to a burst of clobetasol in these circumstances. The schedule is 1 week on, 1 week off.

"A typical situation might be when a rheumatologist calls me and says, ‘I have a patient who got a horrible photosensitive malar rash while outdoors last weekend, and she’s already on maximum-dose systemic therapy.’ I’d say, just give her 1 week of clobetasol on her face; she’ll be better in 3-4 days. But you need to carefully tell your patients that if they’re going to put it on their face they have to follow the rule for face disease: 1 week on, 1 week off," she said.

Cream or ointment? For most patients with autoimmune diseases, pick a topical steroid cream; it’ll result in better compliance. A steroid ointment is preferable when skin hydration is a consideration, as in atopic dermatitis. Because ointments are effectively stronger and more deeply penetrating than creams, a steroid ointment is also the best choice in treating disease involving particularly thick skin, such as palmar or plantar psoriasis, where the medication is employed under occlusion with gloves or socks, Dr. Vleugels explained.

To avoid undertreatment, it’s important to specify on the prescription how much medication the pharmacy is to provide. A 60-g tube of a topical steroid won’t last longer than a week in a patient with a full-body skin eruption; Dr. Vleugels generally orders 120-240 g for such patients. For patients treating lesions on the face or other sensitive areas, she cuts the prescription to 30 g with a single refill unless she’s comfortable with that individual’s adherence.

Topical calcineurin inhibitors have a limited role. Dr. Vleugels considers using 0.3% tacrolimus during patients’ week-long topical steroid breaks if their disease isn’t well controlled during those intervals. She also considers tacrolimus in patients with periorbital skin lesions, where steroid atrophy is a particular concern. Topical pimecrolimus is considerably less effective than tacrolimus, and she never uses pimecrolimus in adults.

"I use these agents much less frequently than topical steroids. They’re often low efficacy for the cost [compared with] a topical steroid, used safely," the dermatologist said.

She reported having no financial conflicts.

SNOWMASS, COLO. - Low-dose methotrexate is highly effective for treatment of antimalarial-resistant discoid lupus or subacute cutaneous lupus erythematosus.

"If you have to pick one thing past Plaquenil [hydroxychloroquine], I’d say try methotrexate," declared Dr. Ruth Ann Vleugels at a symposium sponsored by the American College of Rheumatology. "At our institution, methotrexate is by far the next agent we choose for cutaneous lupus if the patient is able to tolerate it. We have really good luck with it, and it’s easy to prescribe," she said.

Dr. Vleugels has amassed what is believed to be the largest U.S. case series of patients treated with methotrexate for refractory cutaneous lupus erythematosus (LE). The as-yet unpublished series consists of 20 patients, most of whom received between 20 mg/week and 25 mg/week. Most were on oral methotrexate, but, if they experienced troublesome side effects, they were switched to the subcutaneous formulation.

Seventeen of the 20 patients (85%) experienced significant improvement on methotrexate. The drug was steroid sparing in 10 of 12 patients (83%). The response time was typically 8-12 weeks, according to 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, both in Boston.

Although cutaneous LE is not a systemic disease, it’s essential to treat it aggressively from the get-go in order to halt the disease process and prevent irreversible scarring in discoid LE and disfiguring pigment contrast in subacute cutaneous LE, she emphasized.

The first question patients ask upon receiving the diagnosis of discoid LE is, how likely am I to develop systemic lupus erythematosus? The best available data suggest a 5%-10% risk overall, and less than that if the lesions are confined to the head and neck, she said. About one-third of discoid LE patients are antinuclear antibody–positive; this has no bearing on their risk of future systemic lupus erythematosus.

When a patient comes in with mild cutaneous LE that’s not adequately controlled with photoprotection, topical agents, and hydroxychloroquine, Dr. Vleugels may opt for combination antimalarial therapy, adding on quinacrine at 100 mg/day. Quinacrine is not immunosuppressive and has essentially no ocular toxicity. Its two downsides are that it can be obtained only at a compounding pharmacy, and it causes many patients to turn yellow. The yellow hue is more noticeable on light-skinned patients. Fortunately, the color change is completely reversible upon drug discontinuation.

If a patient’s cutaneous LE is a little more serious and it isn’t reined in using hydroxychloroquine as sole systemic therapy, Dr. Vleugels will bypass the add-on quinacrine and go straight to methotrexate because the results are so good.

Not all patients are good candidates for methotrexate, however. And some just don’t want to take an immunosuppressive medication. Under those circumstances, her second-choice option is thalidomide. It’s typically dosed at 25-100 mg once at night because it’s sedating. This is a highly effective drug with Food and Drug Administration approval for multiple myeloma and erythema nodosum leprosum, so cutaneous LE is off-label therapy.

Thalidomide is somewhat difficult to give because it is category X, and cutaneous LE occurs most commonly in young women. Physician participation in the FDA’s System for Thalidomide Education and Prescribing Safety (STEPS) program is mandatory. Pregnancy testing is required. Still, "the paperwork is actually pretty simple," according to Dr. Vleugels.

Thromboembolism is a side effect that seems to be largely confined to cancer patients. The chief limiting side effect in lupus patients is peripheral neuropathy, which has occurred in 25%-33% of treated patients in various series.

"That’s the main reason we have to take patients off this drug. That’s a pretty good chunk of patients, but the other patients do extremely well," the dermatologist noted.

Because thalidomide is not immunosuppressive, it can be added to virtually any other therapies without causing problems.

When thalidomide is not an option, her next choice is mycophenolate mofetil. It’s easier to prescribe, but definitely less effective than thalidomide in cutaneous LE.

Backup add-on systemic agents include dapsone, which is most effective in bullous LE, and acitretin, a potent retinoid with efficacy in cutaneous LE comparable to that of hydroxychloroquine. However, acitretin has a major drawback: It is stored in fat for 3 years and is category X. That means a young woman can’t get pregnant for 3 years after stopping the drug. For this reason, Dr. Vleugels reserves acitretin for men and older women.

Although she is quick to turn to systemic therapy for cutaneous LE, all of her patients start out with a message underscoring the importance of photoprotection, smoking cessation, and – living in Boston – vitamin D supplementation at 2,000 IU/day.

Topical therapy with corticosteroids and tacrolimus, a calcineurin inhibitor which is useful as a break from steroids, is also in place before she considers the introduction of systemic therapy starting with antimalarials.

To prevent lasting scarring in discoid LE patients with scalp involvement, Dr. Vleugels moves beyond systemic therapy, adding intralesional steroid injections. She typically takes triamcinolone (Kenalog) that comes in a concentration of 10 mg/cc, and dilutes it 1-to-1 with normal saline, for a final concentration of 5 mg/cc. She uses 0.1 cc of the diluted product per injection through a 30- or 31-gauge needle, picking the most inflamed areas of the scalp and placing the injections about 1 cm apart.

"One patient can tolerate only about 25 injections per day, sometimes fewer than that," Dr. Vleugels said, eliciting audience gasps. "You’d be surprised: Even our kids with scalp disease can tolerate injections fairly well because of the very small needle we use."

She has the patient return for another series of scalp injections in 5-6 weeks.

Dr. Vleugels reported having no financial conflicts.

SNOWMASS, COLO. - Low-dose methotrexate is highly effective for treatment of antimalarial-resistant discoid lupus or subacute cutaneous lupus erythematosus.

"If you have to pick one thing past Plaquenil [hydroxychloroquine], I’d say try methotrexate," declared Dr. Ruth Ann Vleugels at a symposium sponsored by the American College of Rheumatology. "At our institution, methotrexate is by far the next agent we choose for cutaneous lupus if the patient is able to tolerate it. We have really good luck with it, and it’s easy to prescribe," she said.

Dr. Vleugels has amassed what is believed to be the largest U.S. case series of patients treated with methotrexate for refractory cutaneous lupus erythematosus (LE). The as-yet unpublished series consists of 20 patients, most of whom received between 20 mg/week and 25 mg/week. Most were on oral methotrexate, but, if they experienced troublesome side effects, they were switched to the subcutaneous formulation.

Seventeen of the 20 patients (85%) experienced significant improvement on methotrexate. The drug was steroid sparing in 10 of 12 patients (83%). The response time was typically 8-12 weeks, according to 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, both in Boston.

Although cutaneous LE is not a systemic disease, it’s essential to treat it aggressively from the get-go in order to halt the disease process and prevent irreversible scarring in discoid LE and disfiguring pigment contrast in subacute cutaneous LE, she emphasized.

The first question patients ask upon receiving the diagnosis of discoid LE is, how likely am I to develop systemic lupus erythematosus? The best available data suggest a 5%-10% risk overall, and less than that if the lesions are confined to the head and neck, she said. About one-third of discoid LE patients are antinuclear antibody–positive; this has no bearing on their risk of future systemic lupus erythematosus.

When a patient comes in with mild cutaneous LE that’s not adequately controlled with photoprotection, topical agents, and hydroxychloroquine, Dr. Vleugels may opt for combination antimalarial therapy, adding on quinacrine at 100 mg/day. Quinacrine is not immunosuppressive and has essentially no ocular toxicity. Its two downsides are that it can be obtained only at a compounding pharmacy, and it causes many patients to turn yellow. The yellow hue is more noticeable on light-skinned patients. Fortunately, the color change is completely reversible upon drug discontinuation.

If a patient’s cutaneous LE is a little more serious and it isn’t reined in using hydroxychloroquine as sole systemic therapy, Dr. Vleugels will bypass the add-on quinacrine and go straight to methotrexate because the results are so good.

Not all patients are good candidates for methotrexate, however. And some just don’t want to take an immunosuppressive medication. Under those circumstances, her second-choice option is thalidomide. It’s typically dosed at 25-100 mg once at night because it’s sedating. This is a highly effective drug with Food and Drug Administration approval for multiple myeloma and erythema nodosum leprosum, so cutaneous LE is off-label therapy.

Thalidomide is somewhat difficult to give because it is category X, and cutaneous LE occurs most commonly in young women. Physician participation in the FDA’s System for Thalidomide Education and Prescribing Safety (STEPS) program is mandatory. Pregnancy testing is required. Still, "the paperwork is actually pretty simple," according to Dr. Vleugels.

Thromboembolism is a side effect that seems to be largely confined to cancer patients. The chief limiting side effect in lupus patients is peripheral neuropathy, which has occurred in 25%-33% of treated patients in various series.

"That’s the main reason we have to take patients off this drug. That’s a pretty good chunk of patients, but the other patients do extremely well," the dermatologist noted.

Because thalidomide is not immunosuppressive, it can be added to virtually any other therapies without causing problems.

When thalidomide is not an option, her next choice is mycophenolate mofetil. It’s easier to prescribe, but definitely less effective than thalidomide in cutaneous LE.

Backup add-on systemic agents include dapsone, which is most effective in bullous LE, and acitretin, a potent retinoid with efficacy in cutaneous LE comparable to that of hydroxychloroquine. However, acitretin has a major drawback: It is stored in fat for 3 years and is category X. That means a young woman can’t get pregnant for 3 years after stopping the drug. For this reason, Dr. Vleugels reserves acitretin for men and older women.

Although she is quick to turn to systemic therapy for cutaneous LE, all of her patients start out with a message underscoring the importance of photoprotection, smoking cessation, and – living in Boston – vitamin D supplementation at 2,000 IU/day.

Topical therapy with corticosteroids and tacrolimus, a calcineurin inhibitor which is useful as a break from steroids, is also in place before she considers the introduction of systemic therapy starting with antimalarials.

To prevent lasting scarring in discoid LE patients with scalp involvement, Dr. Vleugels moves beyond systemic therapy, adding intralesional steroid injections. She typically takes triamcinolone (Kenalog) that comes in a concentration of 10 mg/cc, and dilutes it 1-to-1 with normal saline, for a final concentration of 5 mg/cc. She uses 0.1 cc of the diluted product per injection through a 30- or 31-gauge needle, picking the most inflamed areas of the scalp and placing the injections about 1 cm apart.

"One patient can tolerate only about 25 injections per day, sometimes fewer than that," Dr. Vleugels said, eliciting audience gasps. "You’d be surprised: Even our kids with scalp disease can tolerate injections fairly well because of the very small needle we use."

She has the patient return for another series of scalp injections in 5-6 weeks.

Dr. Vleugels reported having no financial conflicts.

SNOWMASS, COLO. - Low-dose methotrexate is highly effective for treatment of antimalarial-resistant discoid lupus or subacute cutaneous lupus erythematosus.

"If you have to pick one thing past Plaquenil [hydroxychloroquine], I’d say try methotrexate," declared Dr. Ruth Ann Vleugels at a symposium sponsored by the American College of Rheumatology. "At our institution, methotrexate is by far the next agent we choose for cutaneous lupus if the patient is able to tolerate it. We have really good luck with it, and it’s easy to prescribe," she said.

Dr. Vleugels has amassed what is believed to be the largest U.S. case series of patients treated with methotrexate for refractory cutaneous lupus erythematosus (LE). The as-yet unpublished series consists of 20 patients, most of whom received between 20 mg/week and 25 mg/week. Most were on oral methotrexate, but, if they experienced troublesome side effects, they were switched to the subcutaneous formulation.

Seventeen of the 20 patients (85%) experienced significant improvement on methotrexate. The drug was steroid sparing in 10 of 12 patients (83%). The response time was typically 8-12 weeks, according to 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, both in Boston.

Although cutaneous LE is not a systemic disease, it’s essential to treat it aggressively from the get-go in order to halt the disease process and prevent irreversible scarring in discoid LE and disfiguring pigment contrast in subacute cutaneous LE, she emphasized.

The first question patients ask upon receiving the diagnosis of discoid LE is, how likely am I to develop systemic lupus erythematosus? The best available data suggest a 5%-10% risk overall, and less than that if the lesions are confined to the head and neck, she said. About one-third of discoid LE patients are antinuclear antibody–positive; this has no bearing on their risk of future systemic lupus erythematosus.

When a patient comes in with mild cutaneous LE that’s not adequately controlled with photoprotection, topical agents, and hydroxychloroquine, Dr. Vleugels may opt for combination antimalarial therapy, adding on quinacrine at 100 mg/day. Quinacrine is not immunosuppressive and has essentially no ocular toxicity. Its two downsides are that it can be obtained only at a compounding pharmacy, and it causes many patients to turn yellow. The yellow hue is more noticeable on light-skinned patients. Fortunately, the color change is completely reversible upon drug discontinuation.

If a patient’s cutaneous LE is a little more serious and it isn’t reined in using hydroxychloroquine as sole systemic therapy, Dr. Vleugels will bypass the add-on quinacrine and go straight to methotrexate because the results are so good.

Not all patients are good candidates for methotrexate, however. And some just don’t want to take an immunosuppressive medication. Under those circumstances, her second-choice option is thalidomide. It’s typically dosed at 25-100 mg once at night because it’s sedating. This is a highly effective drug with Food and Drug Administration approval for multiple myeloma and erythema nodosum leprosum, so cutaneous LE is off-label therapy.

Thalidomide is somewhat difficult to give because it is category X, and cutaneous LE occurs most commonly in young women. Physician participation in the FDA’s System for Thalidomide Education and Prescribing Safety (STEPS) program is mandatory. Pregnancy testing is required. Still, "the paperwork is actually pretty simple," according to Dr. Vleugels.

Thromboembolism is a side effect that seems to be largely confined to cancer patients. The chief limiting side effect in lupus patients is peripheral neuropathy, which has occurred in 25%-33% of treated patients in various series.

"That’s the main reason we have to take patients off this drug. That’s a pretty good chunk of patients, but the other patients do extremely well," the dermatologist noted.

Because thalidomide is not immunosuppressive, it can be added to virtually any other therapies without causing problems.

When thalidomide is not an option, her next choice is mycophenolate mofetil. It’s easier to prescribe, but definitely less effective than thalidomide in cutaneous LE.

Backup add-on systemic agents include dapsone, which is most effective in bullous LE, and acitretin, a potent retinoid with efficacy in cutaneous LE comparable to that of hydroxychloroquine. However, acitretin has a major drawback: It is stored in fat for 3 years and is category X. That means a young woman can’t get pregnant for 3 years after stopping the drug. For this reason, Dr. Vleugels reserves acitretin for men and older women.

Although she is quick to turn to systemic therapy for cutaneous LE, all of her patients start out with a message underscoring the importance of photoprotection, smoking cessation, and – living in Boston – vitamin D supplementation at 2,000 IU/day.

Topical therapy with corticosteroids and tacrolimus, a calcineurin inhibitor which is useful as a break from steroids, is also in place before she considers the introduction of systemic therapy starting with antimalarials.

To prevent lasting scarring in discoid LE patients with scalp involvement, Dr. Vleugels moves beyond systemic therapy, adding intralesional steroid injections. She typically takes triamcinolone (Kenalog) that comes in a concentration of 10 mg/cc, and dilutes it 1-to-1 with normal saline, for a final concentration of 5 mg/cc. She uses 0.1 cc of the diluted product per injection through a 30- or 31-gauge needle, picking the most inflamed areas of the scalp and placing the injections about 1 cm apart.

"One patient can tolerate only about 25 injections per day, sometimes fewer than that," Dr. Vleugels said, eliciting audience gasps. "You’d be surprised: Even our kids with scalp disease can tolerate injections fairly well because of the very small needle we use."

She has the patient return for another series of scalp injections in 5-6 weeks.

Dr. Vleugels reported having no financial conflicts.

SNOWMASS, COLO. – The risk of herpes zoster isn’t raised in rheumatoid arthritis patients who are on a tumor necrosis factor inhibitor, compared with those on nonbiologic disease-modifying antirheumatic drugs, according to a preliminary analysis from by far the largest study to examine the question.

Findings from the same study also suggested that TNF–inhibiting therapy may actually protect against zoster in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease.

Data from two previous, large, population-based studies looking at the risk of herpes zoster in RA patients on anti-TNF biologics reveal discordant conclusions. These conflicting findings prompted Dr. Kevin L. Winthrop and his coinvestigators in the SABER (Safety Assessment of Biologic Therapy) collaboration to examine the issue in their very large data set.

SABER is a retrospective cohort study involving four large U.S. automated health databases. The as-yet-unpublished SABER herpes zoster analysis included more than 35,000 patients with diseases for which TNF inhibitors are indicated.

During 22,215 person-years of follow-up, the crude rate of herpes zoster among RA patients who were new first-time users of an anti-TNF agent was 12.1 cases per 1,000 person-years, which wasn’t significantly different from the 12.8 per 1,000 rate during 7,165 person-years of follow-up in the control group, which comprised RA patients who were failing on methotrexate and adding another conventional DMARD, usually hydroxychloroquine (Plaquenil).

There were no significant differences in zoster rates among the various anti-TNF agents, Dr. Winthrop said at the symposium, which was sponsored by the American College of Rheumatology.

Intriguingly, going on an anti-TNF agent actually appeared to protect against herpes zoster in SABER participants with psoriasis, psoriatic arthritis, or ankylosing spondylitis. During 4,106 person-years of follow-up, their crude rate of zoster was 4.4 cases per 1,000 person-years, an adjusted 36% lower risk than that in patients on a nonbiologic DMARD, whose rate was 6.8 cases per 1,000 person-years during 3,950 person-years of follow-up, according to Dr. Winthrop, an infectious diseases specialist at Oregon Health and Science University, Portland.

Moreover, new users of infliximab or adalimumab for inflammatory bowel disease had an adjusted 20% reduction in risk of zoster, compared with those on azathioprine or 6-mercaptopurine, he added.

An earlier retrospective cohort study involving 20,357 RA patients in the Veterans Affairs health care system found that patients on adalimumab had an adjusted 47% lower risk of zoster, and those on etanercept had a 38% reduction in risk, compared with patients on conventional DMARDs. Patients on infliximab had a 30% increased risk; however, this trend didn’t reach statistical significance (Clin. Infect. Dis. 2009;48:1364-71).

In sharp contrast, investigators from the prospective German RABBIT registry involving 5,040 RA patients reported that adalimumab was associated with a 3-fold increased risk of herpes zoster compared to nonbiologic DMARD therapy. Infliximab had an adjusted 2.4-fold increased risk, which wasn’t statistically significant. Etanercept wasn’t associated with increased risk (JAMA 2009;301:737-44).

The explanation for the discordant findings in RABBIT and the VA study is unclear. The studies did use somewhat different methodologies. Regardless, it’s worth noting that the number of subjects included in the new SABER analysis was larger than for both of the earlier studies put together.

"Look how robust this is," Dr. Winthrop observed. "We have good, good power. Our interpretation is there is no increased risk of zoster with anti-TNF drugs."

Nonetheless, this is a preliminary analysis. The SABER investigators plan to look next at what happened to prednisone dosing when the RA patients went on anti-TNF therapy or an additional nonbiologic DMARD, something they can do with this cohort but couldn’t do in an earlier SABER publication. Dr. Winthrop said he suspects that the prednisone dose was more likely to be reduced or eliminated in the TNF-inhibitor users, and that this might account for the finding that anti-TNF therapy didn’t increase zoster risk. A half-dozen studies have shown that prednisone therapy is associated with an increased risk of herpes zoster.

Dr. Winthrop said it’s his impression that patients who develop herpes zoster while on anti-TNF therapy don’t have a higher rate of disseminated disease or worse outcomes than do those who are not. In the SABER analysis, the rate of hospitalization for zoster was similarly very low in the biologic and nonbiologic treatment groups.

In response to audience questions, he said he believes it makes sense to give herpes zoster vaccine to RA patients starting at 50 years of age. RA per se is a risk factor for zoster, as is prednisone therapy. There is no evidence of any safety issues in vaccinating patients who take any of the standard DMARDs or anti-TNF agents, although there are no definitive data on that score. It’s possible that pharmacologic immunosuppression blunts the vaccine’s efficacy, but that hasn’t been studied.

Dr. Winthrop reported having no financial conflicts.

SNOWMASS, COLO. – The risk of herpes zoster isn’t raised in rheumatoid arthritis patients who are on a tumor necrosis factor inhibitor, compared with those on nonbiologic disease-modifying antirheumatic drugs, according to a preliminary analysis from by far the largest study to examine the question.

Findings from the same study also suggested that TNF–inhibiting therapy may actually protect against zoster in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease.

Data from two previous, large, population-based studies looking at the risk of herpes zoster in RA patients on anti-TNF biologics reveal discordant conclusions. These conflicting findings prompted Dr. Kevin L. Winthrop and his coinvestigators in the SABER (Safety Assessment of Biologic Therapy) collaboration to examine the issue in their very large data set.

SABER is a retrospective cohort study involving four large U.S. automated health databases. The as-yet-unpublished SABER herpes zoster analysis included more than 35,000 patients with diseases for which TNF inhibitors are indicated.

During 22,215 person-years of follow-up, the crude rate of herpes zoster among RA patients who were new first-time users of an anti-TNF agent was 12.1 cases per 1,000 person-years, which wasn’t significantly different from the 12.8 per 1,000 rate during 7,165 person-years of follow-up in the control group, which comprised RA patients who were failing on methotrexate and adding another conventional DMARD, usually hydroxychloroquine (Plaquenil).

There were no significant differences in zoster rates among the various anti-TNF agents, Dr. Winthrop said at the symposium, which was sponsored by the American College of Rheumatology.

Intriguingly, going on an anti-TNF agent actually appeared to protect against herpes zoster in SABER participants with psoriasis, psoriatic arthritis, or ankylosing spondylitis. During 4,106 person-years of follow-up, their crude rate of zoster was 4.4 cases per 1,000 person-years, an adjusted 36% lower risk than that in patients on a nonbiologic DMARD, whose rate was 6.8 cases per 1,000 person-years during 3,950 person-years of follow-up, according to Dr. Winthrop, an infectious diseases specialist at Oregon Health and Science University, Portland.

Moreover, new users of infliximab or adalimumab for inflammatory bowel disease had an adjusted 20% reduction in risk of zoster, compared with those on azathioprine or 6-mercaptopurine, he added.

An earlier retrospective cohort study involving 20,357 RA patients in the Veterans Affairs health care system found that patients on adalimumab had an adjusted 47% lower risk of zoster, and those on etanercept had a 38% reduction in risk, compared with patients on conventional DMARDs. Patients on infliximab had a 30% increased risk; however, this trend didn’t reach statistical significance (Clin. Infect. Dis. 2009;48:1364-71).

In sharp contrast, investigators from the prospective German RABBIT registry involving 5,040 RA patients reported that adalimumab was associated with a 3-fold increased risk of herpes zoster compared to nonbiologic DMARD therapy. Infliximab had an adjusted 2.4-fold increased risk, which wasn’t statistically significant. Etanercept wasn’t associated with increased risk (JAMA 2009;301:737-44).

The explanation for the discordant findings in RABBIT and the VA study is unclear. The studies did use somewhat different methodologies. Regardless, it’s worth noting that the number of subjects included in the new SABER analysis was larger than for both of the earlier studies put together.

"Look how robust this is," Dr. Winthrop observed. "We have good, good power. Our interpretation is there is no increased risk of zoster with anti-TNF drugs."

Nonetheless, this is a preliminary analysis. The SABER investigators plan to look next at what happened to prednisone dosing when the RA patients went on anti-TNF therapy or an additional nonbiologic DMARD, something they can do with this cohort but couldn’t do in an earlier SABER publication. Dr. Winthrop said he suspects that the prednisone dose was more likely to be reduced or eliminated in the TNF-inhibitor users, and that this might account for the finding that anti-TNF therapy didn’t increase zoster risk. A half-dozen studies have shown that prednisone therapy is associated with an increased risk of herpes zoster.

Dr. Winthrop said it’s his impression that patients who develop herpes zoster while on anti-TNF therapy don’t have a higher rate of disseminated disease or worse outcomes than do those who are not. In the SABER analysis, the rate of hospitalization for zoster was similarly very low in the biologic and nonbiologic treatment groups.

In response to audience questions, he said he believes it makes sense to give herpes zoster vaccine to RA patients starting at 50 years of age. RA per se is a risk factor for zoster, as is prednisone therapy. There is no evidence of any safety issues in vaccinating patients who take any of the standard DMARDs or anti-TNF agents, although there are no definitive data on that score. It’s possible that pharmacologic immunosuppression blunts the vaccine’s efficacy, but that hasn’t been studied.

Dr. Winthrop reported having no financial conflicts.

SNOWMASS, COLO. – The risk of herpes zoster isn’t raised in rheumatoid arthritis patients who are on a tumor necrosis factor inhibitor, compared with those on nonbiologic disease-modifying antirheumatic drugs, according to a preliminary analysis from by far the largest study to examine the question.

Findings from the same study also suggested that TNF–inhibiting therapy may actually protect against zoster in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease.

Data from two previous, large, population-based studies looking at the risk of herpes zoster in RA patients on anti-TNF biologics reveal discordant conclusions. These conflicting findings prompted Dr. Kevin L. Winthrop and his coinvestigators in the SABER (Safety Assessment of Biologic Therapy) collaboration to examine the issue in their very large data set.

SABER is a retrospective cohort study involving four large U.S. automated health databases. The as-yet-unpublished SABER herpes zoster analysis included more than 35,000 patients with diseases for which TNF inhibitors are indicated.

During 22,215 person-years of follow-up, the crude rate of herpes zoster among RA patients who were new first-time users of an anti-TNF agent was 12.1 cases per 1,000 person-years, which wasn’t significantly different from the 12.8 per 1,000 rate during 7,165 person-years of follow-up in the control group, which comprised RA patients who were failing on methotrexate and adding another conventional DMARD, usually hydroxychloroquine (Plaquenil).

There were no significant differences in zoster rates among the various anti-TNF agents, Dr. Winthrop said at the symposium, which was sponsored by the American College of Rheumatology.

Intriguingly, going on an anti-TNF agent actually appeared to protect against herpes zoster in SABER participants with psoriasis, psoriatic arthritis, or ankylosing spondylitis. During 4,106 person-years of follow-up, their crude rate of zoster was 4.4 cases per 1,000 person-years, an adjusted 36% lower risk than that in patients on a nonbiologic DMARD, whose rate was 6.8 cases per 1,000 person-years during 3,950 person-years of follow-up, according to Dr. Winthrop, an infectious diseases specialist at Oregon Health and Science University, Portland.

Moreover, new users of infliximab or adalimumab for inflammatory bowel disease had an adjusted 20% reduction in risk of zoster, compared with those on azathioprine or 6-mercaptopurine, he added.

An earlier retrospective cohort study involving 20,357 RA patients in the Veterans Affairs health care system found that patients on adalimumab had an adjusted 47% lower risk of zoster, and those on etanercept had a 38% reduction in risk, compared with patients on conventional DMARDs. Patients on infliximab had a 30% increased risk; however, this trend didn’t reach statistical significance (Clin. Infect. Dis. 2009;48:1364-71).

In sharp contrast, investigators from the prospective German RABBIT registry involving 5,040 RA patients reported that adalimumab was associated with a 3-fold increased risk of herpes zoster compared to nonbiologic DMARD therapy. Infliximab had an adjusted 2.4-fold increased risk, which wasn’t statistically significant. Etanercept wasn’t associated with increased risk (JAMA 2009;301:737-44).

The explanation for the discordant findings in RABBIT and the VA study is unclear. The studies did use somewhat different methodologies. Regardless, it’s worth noting that the number of subjects included in the new SABER analysis was larger than for both of the earlier studies put together.

"Look how robust this is," Dr. Winthrop observed. "We have good, good power. Our interpretation is there is no increased risk of zoster with anti-TNF drugs."

Nonetheless, this is a preliminary analysis. The SABER investigators plan to look next at what happened to prednisone dosing when the RA patients went on anti-TNF therapy or an additional nonbiologic DMARD, something they can do with this cohort but couldn’t do in an earlier SABER publication. Dr. Winthrop said he suspects that the prednisone dose was more likely to be reduced or eliminated in the TNF-inhibitor users, and that this might account for the finding that anti-TNF therapy didn’t increase zoster risk. A half-dozen studies have shown that prednisone therapy is associated with an increased risk of herpes zoster.

Dr. Winthrop said it’s his impression that patients who develop herpes zoster while on anti-TNF therapy don’t have a higher rate of disseminated disease or worse outcomes than do those who are not. In the SABER analysis, the rate of hospitalization for zoster was similarly very low in the biologic and nonbiologic treatment groups.

In response to audience questions, he said he believes it makes sense to give herpes zoster vaccine to RA patients starting at 50 years of age. RA per se is a risk factor for zoster, as is prednisone therapy. There is no evidence of any safety issues in vaccinating patients who take any of the standard DMARDs or anti-TNF agents, although there are no definitive data on that score. It’s possible that pharmacologic immunosuppression blunts the vaccine’s efficacy, but that hasn’t been studied.

Dr. Winthrop reported having no financial conflicts.