Psoriasis

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.

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

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

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

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

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

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

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

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

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

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

The authors said they had no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

The authors said they had no relevant financial disclosures.

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

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

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

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

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

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

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

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

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

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

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

The authors said they had no relevant financial disclosures.

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

In this month's program, Dr. Alexa B. Kimball discusses why psoriasis treatment shouldn't be delayed.

Dr. James M. Spencer offers his insights on the pros and cons of bringing radiation treatment back to the dermatologist's office.

Then, a marketing guru offers tips on how to keep cosmetic patients coming back.

Cosmetic counter host Dr. Lily Talakoub explains what it really means when a product claims to be all "natural."

And finally, Dr. Alan Rockoff shares one of the more humorous places people have gone to read his new book.

In this month's program, Dr. Alexa B. Kimball discusses why psoriasis treatment shouldn't be delayed.

Dr. James M. Spencer offers his insights on the pros and cons of bringing radiation treatment back to the dermatologist's office.

Then, a marketing guru offers tips on how to keep cosmetic patients coming back.

Cosmetic counter host Dr. Lily Talakoub explains what it really means when a product claims to be all "natural."

And finally, Dr. Alan Rockoff shares one of the more humorous places people have gone to read his new book.

In this month's program, Dr. Alexa B. Kimball discusses why psoriasis treatment shouldn't be delayed.

Dr. James M. Spencer offers his insights on the pros and cons of bringing radiation treatment back to the dermatologist's office.

Then, a marketing guru offers tips on how to keep cosmetic patients coming back.

Cosmetic counter host Dr. Lily Talakoub explains what it really means when a product claims to be all "natural."

And finally, Dr. Alan Rockoff shares one of the more humorous places people have gone to read his new book.

Skin & Allergy News editor Amy Pfeiffer and Terry Rudd review hot news in dermatology with the experts in this month's Skinny Vodcast.

Skin & Allergy News editor Amy Pfeiffer and Terry Rudd review hot news in dermatology with the experts in this month's Skinny Vodcast.

Skin & Allergy News editor Amy Pfeiffer and Terry Rudd review hot news in dermatology with the experts in this month's Skinny Vodcast.

The National Psoriasis Foundation has launched a "seal of approval" program for over-the-counter products that an expert panel has determined to be "helpful in the management of psoriasis and psoriatic arthritis," according to the organization’s website.

The program’s objective "is to improve the quality of life for people who live with psoriasis and psoriatic arthritis," according to the NPF.

Under the seal program, companies submit over-the-counter products for approval, with an annual, nonrefundable application fee. A panel of dermatologists and other experts review the product and determine whether it meets required criteria, including the ability to hydrate skin, reduce redness, reduce joint pain, and/or provide aid for patients with psoriatic arthritis, according to a release announcing the launch of the program.

The four-person panel also reviews the ingredients and data on its safety, toxicity, and formulation.

Once approved, the seal can remain on the product for 2 years. The application fee is $5,000, which covers honoraria and time spent reviewing the clinical information that the company provides, plus an additional fee of $10,000 per year for each product that earns the seal, according to Jackie Groah, director of strategic alliances at the NPF. The reviewers will excuse themselves from the review if they have had any dealings with the company applying for the seal, she said in an interview.

Five scalp psoriasis products manufactured by Neutrogena and a gel product for patients with plaque psoriasis, manufactured by Alva-Amco, were the first products to receive the seal. The seal can be awarded to personal care and household products, fabrics, and devices, according to the NPF.

Click here for more details about the program.

The National Psoriasis Foundation has launched a "seal of approval" program for over-the-counter products that an expert panel has determined to be "helpful in the management of psoriasis and psoriatic arthritis," according to the organization’s website.

The program’s objective "is to improve the quality of life for people who live with psoriasis and psoriatic arthritis," according to the NPF.

Under the seal program, companies submit over-the-counter products for approval, with an annual, nonrefundable application fee. A panel of dermatologists and other experts review the product and determine whether it meets required criteria, including the ability to hydrate skin, reduce redness, reduce joint pain, and/or provide aid for patients with psoriatic arthritis, according to a release announcing the launch of the program.

The four-person panel also reviews the ingredients and data on its safety, toxicity, and formulation.

Once approved, the seal can remain on the product for 2 years. The application fee is $5,000, which covers honoraria and time spent reviewing the clinical information that the company provides, plus an additional fee of $10,000 per year for each product that earns the seal, according to Jackie Groah, director of strategic alliances at the NPF. The reviewers will excuse themselves from the review if they have had any dealings with the company applying for the seal, she said in an interview.

Five scalp psoriasis products manufactured by Neutrogena and a gel product for patients with plaque psoriasis, manufactured by Alva-Amco, were the first products to receive the seal. The seal can be awarded to personal care and household products, fabrics, and devices, according to the NPF.

Click here for more details about the program.

The National Psoriasis Foundation has launched a "seal of approval" program for over-the-counter products that an expert panel has determined to be "helpful in the management of psoriasis and psoriatic arthritis," according to the organization’s website.

The program’s objective "is to improve the quality of life for people who live with psoriasis and psoriatic arthritis," according to the NPF.

Under the seal program, companies submit over-the-counter products for approval, with an annual, nonrefundable application fee. A panel of dermatologists and other experts review the product and determine whether it meets required criteria, including the ability to hydrate skin, reduce redness, reduce joint pain, and/or provide aid for patients with psoriatic arthritis, according to a release announcing the launch of the program.

The four-person panel also reviews the ingredients and data on its safety, toxicity, and formulation.

Once approved, the seal can remain on the product for 2 years. The application fee is $5,000, which covers honoraria and time spent reviewing the clinical information that the company provides, plus an additional fee of $10,000 per year for each product that earns the seal, according to Jackie Groah, director of strategic alliances at the NPF. The reviewers will excuse themselves from the review if they have had any dealings with the company applying for the seal, she said in an interview.

Five scalp psoriasis products manufactured by Neutrogena and a gel product for patients with plaque psoriasis, manufactured by Alva-Amco, were the first products to receive the seal. The seal can be awarded to personal care and household products, fabrics, and devices, according to the NPF.

Click here for more details about the program.

As a pediatric dermatologist, Dr. Robert A. Silverman is all too familiar with this scenario: A child is referred to him with a diagnosis of nail fungus, and the parents are frustrated that the oral antifungal agents did not work.

What bothers him the most is not the antifungals, but that the patients didn’t need them to begin with because the child didn’t have a fungal infection, he said at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Several conditions of the nail in children can easily be mistaken for fungal infections.

Dr. Silverman of the department of pediatrics at Georgetown University Medical Center in Washington discussed how to distinguish fungal disease mimics from other pediatric nail conditions in children.

Onychomycosis, the most common nail infection in adults, is not all that common in children, Dr. Silverman said. Studies have shown the prevalence in children to be less than 3% in developed countries, although it is increased among children who have Down syndrome and HIV, or children from households with moccasintype Trichophyton rubrum. Clinical variants are similar to those that occur in adults, such as white superficial onychomycosis, distal lateral subungual onychomycosis, proximal subungual onychomycosis, and endonyx onychomycosis.

Other conditions that may be mistaken for fungal infections include:

• Psoriasis. Nail findings in patients who have psoriasis can be misinterpreted as fungal disease. Telltale signs of psoriasis in the nails, however, are large, irregular pits and the oil spot sign.

• Subungual tumors. These include subungual exostosis and onychomatricoma. These benign growths push on the skin surface, leading to separation of the nail. "Some people think fungus when it’s really a tumor of the underlying bone," Dr. Silverman said.

• Pachyonychia congenita. Though often confused with fungal disease, this condition, which involves a single thickened toenail, is somewhat rare. "If someone came in with a thick toenail, I’d culture him or her," Dr. Silverman said. "If the culture is negative, then you have to start thinking of these other conditions."

• Alopecia areata. Children may have nail signs of alopecia areata before hair loss occurs. In alopecia areata, the nail surface is studded to near confluence with tiny pits, also known as Scotch plaid nails. Also, the nail will have lost its luster and has a sandpaperlike texture.

"If you see what looks like alopecia areata of the nail, but don’t see any hair findings, you ought to scrape the nail to rule out fungus, because fungus can look like alopecia areata of the nails," Dr. Silverman said. "And, of course, then you would want to treat it."

Treatment for fungal infections requires the use of an oral agent for 6-12 weeks, so Dr. Silverman emphasized the importance of obtaining a culture. "If you’re going to treat someone for that length of time, it makes sense to know exactly what you’re treating," he said.

Also, Dr. Silverman said, any time he sees that a child’s parent appears to have a fungal infection, he considers that to be a red flag when trying to diagnose the patient.

As a pediatric dermatologist, Dr. Robert A. Silverman is all too familiar with this scenario: A child is referred to him with a diagnosis of nail fungus, and the parents are frustrated that the oral antifungal agents did not work.

What bothers him the most is not the antifungals, but that the patients didn’t need them to begin with because the child didn’t have a fungal infection, he said at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Several conditions of the nail in children can easily be mistaken for fungal infections.

Dr. Silverman of the department of pediatrics at Georgetown University Medical Center in Washington discussed how to distinguish fungal disease mimics from other pediatric nail conditions in children.

Onychomycosis, the most common nail infection in adults, is not all that common in children, Dr. Silverman said. Studies have shown the prevalence in children to be less than 3% in developed countries, although it is increased among children who have Down syndrome and HIV, or children from households with moccasintype Trichophyton rubrum. Clinical variants are similar to those that occur in adults, such as white superficial onychomycosis, distal lateral subungual onychomycosis, proximal subungual onychomycosis, and endonyx onychomycosis.

Other conditions that may be mistaken for fungal infections include:

• Psoriasis. Nail findings in patients who have psoriasis can be misinterpreted as fungal disease. Telltale signs of psoriasis in the nails, however, are large, irregular pits and the oil spot sign.

• Subungual tumors. These include subungual exostosis and onychomatricoma. These benign growths push on the skin surface, leading to separation of the nail. "Some people think fungus when it’s really a tumor of the underlying bone," Dr. Silverman said.

• Pachyonychia congenita. Though often confused with fungal disease, this condition, which involves a single thickened toenail, is somewhat rare. "If someone came in with a thick toenail, I’d culture him or her," Dr. Silverman said. "If the culture is negative, then you have to start thinking of these other conditions."

• Alopecia areata. Children may have nail signs of alopecia areata before hair loss occurs. In alopecia areata, the nail surface is studded to near confluence with tiny pits, also known as Scotch plaid nails. Also, the nail will have lost its luster and has a sandpaperlike texture.

"If you see what looks like alopecia areata of the nail, but don’t see any hair findings, you ought to scrape the nail to rule out fungus, because fungus can look like alopecia areata of the nails," Dr. Silverman said. "And, of course, then you would want to treat it."

Treatment for fungal infections requires the use of an oral agent for 6-12 weeks, so Dr. Silverman emphasized the importance of obtaining a culture. "If you’re going to treat someone for that length of time, it makes sense to know exactly what you’re treating," he said.

Also, Dr. Silverman said, any time he sees that a child’s parent appears to have a fungal infection, he considers that to be a red flag when trying to diagnose the patient.

As a pediatric dermatologist, Dr. Robert A. Silverman is all too familiar with this scenario: A child is referred to him with a diagnosis of nail fungus, and the parents are frustrated that the oral antifungal agents did not work.

What bothers him the most is not the antifungals, but that the patients didn’t need them to begin with because the child didn’t have a fungal infection, he said at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Several conditions of the nail in children can easily be mistaken for fungal infections.

Dr. Silverman of the department of pediatrics at Georgetown University Medical Center in Washington discussed how to distinguish fungal disease mimics from other pediatric nail conditions in children.

Onychomycosis, the most common nail infection in adults, is not all that common in children, Dr. Silverman said. Studies have shown the prevalence in children to be less than 3% in developed countries, although it is increased among children who have Down syndrome and HIV, or children from households with moccasintype Trichophyton rubrum. Clinical variants are similar to those that occur in adults, such as white superficial onychomycosis, distal lateral subungual onychomycosis, proximal subungual onychomycosis, and endonyx onychomycosis.

Other conditions that may be mistaken for fungal infections include:

• Psoriasis. Nail findings in patients who have psoriasis can be misinterpreted as fungal disease. Telltale signs of psoriasis in the nails, however, are large, irregular pits and the oil spot sign.

• Subungual tumors. These include subungual exostosis and onychomatricoma. These benign growths push on the skin surface, leading to separation of the nail. "Some people think fungus when it’s really a tumor of the underlying bone," Dr. Silverman said.

• Pachyonychia congenita. Though often confused with fungal disease, this condition, which involves a single thickened toenail, is somewhat rare. "If someone came in with a thick toenail, I’d culture him or her," Dr. Silverman said. "If the culture is negative, then you have to start thinking of these other conditions."

• Alopecia areata. Children may have nail signs of alopecia areata before hair loss occurs. In alopecia areata, the nail surface is studded to near confluence with tiny pits, also known as Scotch plaid nails. Also, the nail will have lost its luster and has a sandpaperlike texture.

"If you see what looks like alopecia areata of the nail, but don’t see any hair findings, you ought to scrape the nail to rule out fungus, because fungus can look like alopecia areata of the nails," Dr. Silverman said. "And, of course, then you would want to treat it."

Treatment for fungal infections requires the use of an oral agent for 6-12 weeks, so Dr. Silverman emphasized the importance of obtaining a culture. "If you’re going to treat someone for that length of time, it makes sense to know exactly what you’re treating," he said.

Also, Dr. Silverman said, any time he sees that a child’s parent appears to have a fungal infection, he considers that to be a red flag when trying to diagnose the patient.

WAIKOLOA, HAWAII – Joint pain arising in a patient with psoriasis is by no means necessarily due to psoriatic arthritis.

Psoriasis patients can get osteoarthritis or rheumatoid arthritis, just like individuals without the skin disease. The distribution pattern of affected joints provides a useful guide as to which arthropathy is involved.

Bruce Jancin/Elsevier Global Medical News

"When a patient who’s got psoriasis comes to me and says, ‘I have a tremendous amount of joint pain,’ the first place I look is the heel. Heel involvement doesn’t happen very often in rheumatoid arthritis. If the heel hurts, it’s probable that the patient has dactylitis and some form of psoriatic arthritis," according to Dr. Daniel E. Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

Another useful clue: Psoriatic arthritis often affects the distal phalangeal joints of the fingers and toes, with accompanying characteristic psoriatic nail changes, but it spares the metacarpophalangeal (MCP) joints. In contrast, MCP involvement is a typical feature of rheumatoid arthritis, he explained at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

"If only we understood why one joint tends to be affected and not another, we would sure know a whole lot more about psoriatic arthritis, and rheumatoid arthritis for that matter," Dr. Furst observed.

Involvement of the distal interphalangeal (DIP) joints is a common feature in osteoarthritis as well as psoriatic arthritis. However, psoriatic arthritis, unlike osteoarthritis, is an inflammatory arthritis. The affected fingers and toes in a patient with psoriatic arthritis often develop a painful, red, warm, sausage-like swelling of the soft tissue on the entire digit.

"If there’s erythema and squishiness when you push on a painful joint, that’s synovitis, not osteoarthritis," the rheumatologist noted.

Also, osteoarthritis has a strong tendency to involve the carpometacarpal joint of the thumb, a site spared in psoriatic arthritis, he continued.

Psoriatic arthritis often first shows up as a monoarticular, asymmetric arthritis of a larger joint, such as the knee, ankle, or wrist. Rheumatoid arthritis tends to come on much stronger.

"In rheumatoid arthritis, it’s frequently all at once. The patient will say, ‘In a week I went from nothing to pain everywhere.’ Not so in psoriatic arthritis," according to Dr. Furst.

Spondyloarthropathy is common in psoriatic arthritis. It often takes the form of a spondylitis characterized by asymmetric thickening and calcification of the longitudinal ligaments of the spine, resulting in asymmetric syndesmophytes on imaging. The result is a painful and/or stiff low back.

Psoriatic arthritis is widely thought of as a rheumatoid factor–negative disease, but that’s not strictly true. Roughly 15% of psoriatic arthritis patients are rheumatoid factor–positive.

Differentiating psoriatic arthritis from other types of arthritis that occur in psoriasis patients is important from a treatment standpoint. Psoriatic arthritis causes much more bony destruction than recognized until fairly recently, twice as much as rheumatoid arthritis by some measures. The nonbiologic disease-modifying antirheumatic drugs are only marginally effective for joint disease in psoriatic arthritis patients, with the exception of leflunomide (Arava), which has fair benefit for the peripheral arthritis but less for the skin disease.

At present, the tumor necrosis factor (TNF) inhibitors are the most effective agents available for peripheral and axial joint disease in psoriatic arthritis. But the response can be less impressive than in patients with psoriasis-only or rheumatoid arthritis. New therapies on the horizon include agents targeting the inflammatory cytokines interleukins-6, -12, and -15, as well as orally administered small molecules that inhibit Janus kinase, spleen tyrosine kinase, TNF-alpha converting enzyme, or mitogen-activated protein kinase.

"There’s a lot of stuff coming down the pike, including new drugs which have mechanisms of action very different from those most extant in psoriasis. Some of it is going to work. But so far we really don’t know which of it will," Dr. Furst said.

He reported that he serves as a consultant to or recipient of research grants from more than a dozen pharmaceutical companies and the National Institutes of Health.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Joint pain arising in a patient with psoriasis is by no means necessarily due to psoriatic arthritis.

Psoriasis patients can get osteoarthritis or rheumatoid arthritis, just like individuals without the skin disease. The distribution pattern of affected joints provides a useful guide as to which arthropathy is involved.

Bruce Jancin/Elsevier Global Medical News

"When a patient who’s got psoriasis comes to me and says, ‘I have a tremendous amount of joint pain,’ the first place I look is the heel. Heel involvement doesn’t happen very often in rheumatoid arthritis. If the heel hurts, it’s probable that the patient has dactylitis and some form of psoriatic arthritis," according to Dr. Daniel E. Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

Another useful clue: Psoriatic arthritis often affects the distal phalangeal joints of the fingers and toes, with accompanying characteristic psoriatic nail changes, but it spares the metacarpophalangeal (MCP) joints. In contrast, MCP involvement is a typical feature of rheumatoid arthritis, he explained at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

"If only we understood why one joint tends to be affected and not another, we would sure know a whole lot more about psoriatic arthritis, and rheumatoid arthritis for that matter," Dr. Furst observed.

Involvement of the distal interphalangeal (DIP) joints is a common feature in osteoarthritis as well as psoriatic arthritis. However, psoriatic arthritis, unlike osteoarthritis, is an inflammatory arthritis. The affected fingers and toes in a patient with psoriatic arthritis often develop a painful, red, warm, sausage-like swelling of the soft tissue on the entire digit.

"If there’s erythema and squishiness when you push on a painful joint, that’s synovitis, not osteoarthritis," the rheumatologist noted.

Also, osteoarthritis has a strong tendency to involve the carpometacarpal joint of the thumb, a site spared in psoriatic arthritis, he continued.

Psoriatic arthritis often first shows up as a monoarticular, asymmetric arthritis of a larger joint, such as the knee, ankle, or wrist. Rheumatoid arthritis tends to come on much stronger.

"In rheumatoid arthritis, it’s frequently all at once. The patient will say, ‘In a week I went from nothing to pain everywhere.’ Not so in psoriatic arthritis," according to Dr. Furst.

Spondyloarthropathy is common in psoriatic arthritis. It often takes the form of a spondylitis characterized by asymmetric thickening and calcification of the longitudinal ligaments of the spine, resulting in asymmetric syndesmophytes on imaging. The result is a painful and/or stiff low back.

Psoriatic arthritis is widely thought of as a rheumatoid factor–negative disease, but that’s not strictly true. Roughly 15% of psoriatic arthritis patients are rheumatoid factor–positive.

Differentiating psoriatic arthritis from other types of arthritis that occur in psoriasis patients is important from a treatment standpoint. Psoriatic arthritis causes much more bony destruction than recognized until fairly recently, twice as much as rheumatoid arthritis by some measures. The nonbiologic disease-modifying antirheumatic drugs are only marginally effective for joint disease in psoriatic arthritis patients, with the exception of leflunomide (Arava), which has fair benefit for the peripheral arthritis but less for the skin disease.

At present, the tumor necrosis factor (TNF) inhibitors are the most effective agents available for peripheral and axial joint disease in psoriatic arthritis. But the response can be less impressive than in patients with psoriasis-only or rheumatoid arthritis. New therapies on the horizon include agents targeting the inflammatory cytokines interleukins-6, -12, and -15, as well as orally administered small molecules that inhibit Janus kinase, spleen tyrosine kinase, TNF-alpha converting enzyme, or mitogen-activated protein kinase.

"There’s a lot of stuff coming down the pike, including new drugs which have mechanisms of action very different from those most extant in psoriasis. Some of it is going to work. But so far we really don’t know which of it will," Dr. Furst said.

He reported that he serves as a consultant to or recipient of research grants from more than a dozen pharmaceutical companies and the National Institutes of Health.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Joint pain arising in a patient with psoriasis is by no means necessarily due to psoriatic arthritis.

Psoriasis patients can get osteoarthritis or rheumatoid arthritis, just like individuals without the skin disease. The distribution pattern of affected joints provides a useful guide as to which arthropathy is involved.

Bruce Jancin/Elsevier Global Medical News

"When a patient who’s got psoriasis comes to me and says, ‘I have a tremendous amount of joint pain,’ the first place I look is the heel. Heel involvement doesn’t happen very often in rheumatoid arthritis. If the heel hurts, it’s probable that the patient has dactylitis and some form of psoriatic arthritis," according to Dr. Daniel E. Furst, the Carl M. Pearson professor of rheumatology at the University of California, Los Angeles.

Another useful clue: Psoriatic arthritis often affects the distal phalangeal joints of the fingers and toes, with accompanying characteristic psoriatic nail changes, but it spares the metacarpophalangeal (MCP) joints. In contrast, MCP involvement is a typical feature of rheumatoid arthritis, he explained at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).

"If only we understood why one joint tends to be affected and not another, we would sure know a whole lot more about psoriatic arthritis, and rheumatoid arthritis for that matter," Dr. Furst observed.

Involvement of the distal interphalangeal (DIP) joints is a common feature in osteoarthritis as well as psoriatic arthritis. However, psoriatic arthritis, unlike osteoarthritis, is an inflammatory arthritis. The affected fingers and toes in a patient with psoriatic arthritis often develop a painful, red, warm, sausage-like swelling of the soft tissue on the entire digit.

"If there’s erythema and squishiness when you push on a painful joint, that’s synovitis, not osteoarthritis," the rheumatologist noted.

Also, osteoarthritis has a strong tendency to involve the carpometacarpal joint of the thumb, a site spared in psoriatic arthritis, he continued.

Psoriatic arthritis often first shows up as a monoarticular, asymmetric arthritis of a larger joint, such as the knee, ankle, or wrist. Rheumatoid arthritis tends to come on much stronger.

"In rheumatoid arthritis, it’s frequently all at once. The patient will say, ‘In a week I went from nothing to pain everywhere.’ Not so in psoriatic arthritis," according to Dr. Furst.

Spondyloarthropathy is common in psoriatic arthritis. It often takes the form of a spondylitis characterized by asymmetric thickening and calcification of the longitudinal ligaments of the spine, resulting in asymmetric syndesmophytes on imaging. The result is a painful and/or stiff low back.

Psoriatic arthritis is widely thought of as a rheumatoid factor–negative disease, but that’s not strictly true. Roughly 15% of psoriatic arthritis patients are rheumatoid factor–positive.

Differentiating psoriatic arthritis from other types of arthritis that occur in psoriasis patients is important from a treatment standpoint. Psoriatic arthritis causes much more bony destruction than recognized until fairly recently, twice as much as rheumatoid arthritis by some measures. The nonbiologic disease-modifying antirheumatic drugs are only marginally effective for joint disease in psoriatic arthritis patients, with the exception of leflunomide (Arava), which has fair benefit for the peripheral arthritis but less for the skin disease.

At present, the tumor necrosis factor (TNF) inhibitors are the most effective agents available for peripheral and axial joint disease in psoriatic arthritis. But the response can be less impressive than in patients with psoriasis-only or rheumatoid arthritis. New therapies on the horizon include agents targeting the inflammatory cytokines interleukins-6, -12, and -15, as well as orally administered small molecules that inhibit Janus kinase, spleen tyrosine kinase, TNF-alpha converting enzyme, or mitogen-activated protein kinase.

"There’s a lot of stuff coming down the pike, including new drugs which have mechanisms of action very different from those most extant in psoriasis. Some of it is going to work. But so far we really don’t know which of it will," Dr. Furst said.

He reported that he serves as a consultant to or recipient of research grants from more than a dozen pharmaceutical companies and the National Institutes of Health.

SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Multiple studies have found that psoriasis has a greater impact on women than men, and a new finding that women with psoriasis are less likely to become pregnant adds to the list of disease-related concerns.

Dr. Jennifer C. Cather and her colleagues recently completed a claims database study that found psoriasis to be significantly associated with lower rates of pregnancy and live births in women aged 35 or younger.

The Abbott-funded study matched 30,733 pairs (1:1) of women with and without psoriasis, said Dr. Cather at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Overall, women with psoriasis were found to have lower rates of pregnancy (3.1% vs. 3.6%) and live births (1.4% vs. 2.1%), compared with the women without psoriasis.

Photo Copyright Elsevier 2012

 In the 7,374 matched pairs of women aged 35 or younger, the psoriasis patients had a 22% lower likelihood of pregnancy and a 39% lower likelihood of having a live birth, compared with the patients without psoriasis.

Three other recent studies on pregnancy outcomes in psoriasis offer conflicting findings; however, Dr. Cather noted that the study populations were very different for each.

The first study found that pregnant women with psoriasis are at an increased risk of having preterm delivery and low birth weight infants.

Dr. Cather reported the findings of the U.S. study of 162 pregnancies in 122 women with psoriasis, compared with 501 pregnancies in 290 women without psoriasis. The women with psoriasis were found to have a 1.89 increased risk in odds of having a poor outcome composite, compared with the patients without psoriasis (J. Invest. Dermatol. 2012;132:85-91). Psoriasis was not found to be associated with having a caesarian delivery, preeclampsia/eclampsia, or spontaneous abortion.

However, the opposite was found in a European study of 68 deliveries in 35 women with moderate-to-severe psoriasis, compared with 237 deliveries in 236 women without psoriasis. Psoriasis patients “had a higher mean of past spontaneous and induced abortions than controls,” noted Dr. Cather, who is in private practice in Dallas. The psoriasis patients also had an increased rate of pregnancy-induced hypertension, premature rupture of the membranes, large-for-gestational age babies, and macrosomia (J. Eur. Acad. Dermatol. Venereol. 2011;25:1041-7).

In the third study, 1,463 mothers with psoriasis were compared with 11,704 control patients. Pregnant Taiwanese women with psoriasis were found to have a 1.4 times increased risk of having low birth weight infants, compared with controls. Mild psoriasis did not increase the risk of low birth weight, preterm birth, small-for-gestational age infants, caesarian section, or preeclampsia/eclampsia (J. Am. Acad. Dermatol. 2011;64:71-7).

Dr. Cather noted that more studies are needed to assess the true impact of psoriasis on pregnancy.

She disclosed that she serves as a consultant to Abbott, Amgen, Centocor, and has received research grants from Amgen, Celgene, and Pfizer. SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Multiple studies have found that psoriasis has a greater impact on women than men, and a new finding that women with psoriasis are less likely to become pregnant adds to the list of disease-related concerns.

Dr. Jennifer C. Cather and her colleagues recently completed a claims database study that found psoriasis to be significantly associated with lower rates of pregnancy and live births in women aged 35 or younger.

The Abbott-funded study matched 30,733 pairs (1:1) of women with and without psoriasis, said Dr. Cather at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Overall, women with psoriasis were found to have lower rates of pregnancy (3.1% vs. 3.6%) and live births (1.4% vs. 2.1%), compared with the women without psoriasis.

Photo Copyright Elsevier 2012

 In the 7,374 matched pairs of women aged 35 or younger, the psoriasis patients had a 22% lower likelihood of pregnancy and a 39% lower likelihood of having a live birth, compared with the patients without psoriasis.

Three other recent studies on pregnancy outcomes in psoriasis offer conflicting findings; however, Dr. Cather noted that the study populations were very different for each.

The first study found that pregnant women with psoriasis are at an increased risk of having preterm delivery and low birth weight infants.

Dr. Cather reported the findings of the U.S. study of 162 pregnancies in 122 women with psoriasis, compared with 501 pregnancies in 290 women without psoriasis. The women with psoriasis were found to have a 1.89 increased risk in odds of having a poor outcome composite, compared with the patients without psoriasis (J. Invest. Dermatol. 2012;132:85-91). Psoriasis was not found to be associated with having a caesarian delivery, preeclampsia/eclampsia, or spontaneous abortion.

However, the opposite was found in a European study of 68 deliveries in 35 women with moderate-to-severe psoriasis, compared with 237 deliveries in 236 women without psoriasis. Psoriasis patients “had a higher mean of past spontaneous and induced abortions than controls,” noted Dr. Cather, who is in private practice in Dallas. The psoriasis patients also had an increased rate of pregnancy-induced hypertension, premature rupture of the membranes, large-for-gestational age babies, and macrosomia (J. Eur. Acad. Dermatol. Venereol. 2011;25:1041-7).

In the third study, 1,463 mothers with psoriasis were compared with 11,704 control patients. Pregnant Taiwanese women with psoriasis were found to have a 1.4 times increased risk of having low birth weight infants, compared with controls. Mild psoriasis did not increase the risk of low birth weight, preterm birth, small-for-gestational age infants, caesarian section, or preeclampsia/eclampsia (J. Am. Acad. Dermatol. 2011;64:71-7).

Dr. Cather noted that more studies are needed to assess the true impact of psoriasis on pregnancy.

She disclosed that she serves as a consultant to Abbott, Amgen, Centocor, and has received research grants from Amgen, Celgene, and Pfizer. SDEF and this news organization are owned by Elsevier.

WAIKOLOA, HAWAII – Multiple studies have found that psoriasis has a greater impact on women than men, and a new finding that women with psoriasis are less likely to become pregnant adds to the list of disease-related concerns.

Dr. Jennifer C. Cather and her colleagues recently completed a claims database study that found psoriasis to be significantly associated with lower rates of pregnancy and live births in women aged 35 or younger.

The Abbott-funded study matched 30,733 pairs (1:1) of women with and without psoriasis, said Dr. Cather at the annual Hawaii Dermatology Seminar, sponsored by Skin Disease Education Foundation (SDEF). Overall, women with psoriasis were found to have lower rates of pregnancy (3.1% vs. 3.6%) and live births (1.4% vs. 2.1%), compared with the women without psoriasis.

Photo Copyright Elsevier 2012

 In the 7,374 matched pairs of women aged 35 or younger, the psoriasis patients had a 22% lower likelihood of pregnancy and a 39% lower likelihood of having a live birth, compared with the patients without psoriasis.

Three other recent studies on pregnancy outcomes in psoriasis offer conflicting findings; however, Dr. Cather noted that the study populations were very different for each.

The first study found that pregnant women with psoriasis are at an increased risk of having preterm delivery and low birth weight infants.

Dr. Cather reported the findings of the U.S. study of 162 pregnancies in 122 women with psoriasis, compared with 501 pregnancies in 290 women without psoriasis. The women with psoriasis were found to have a 1.89 increased risk in odds of having a poor outcome composite, compared with the patients without psoriasis (J. Invest. Dermatol. 2012;132:85-91). Psoriasis was not found to be associated with having a caesarian delivery, preeclampsia/eclampsia, or spontaneous abortion.

However, the opposite was found in a European study of 68 deliveries in 35 women with moderate-to-severe psoriasis, compared with 237 deliveries in 236 women without psoriasis. Psoriasis patients “had a higher mean of past spontaneous and induced abortions than controls,” noted Dr. Cather, who is in private practice in Dallas. The psoriasis patients also had an increased rate of pregnancy-induced hypertension, premature rupture of the membranes, large-for-gestational age babies, and macrosomia (J. Eur. Acad. Dermatol. Venereol. 2011;25:1041-7).

In the third study, 1,463 mothers with psoriasis were compared with 11,704 control patients. Pregnant Taiwanese women with psoriasis were found to have a 1.4 times increased risk of having low birth weight infants, compared with controls. Mild psoriasis did not increase the risk of low birth weight, preterm birth, small-for-gestational age infants, caesarian section, or preeclampsia/eclampsia (J. Am. Acad. Dermatol. 2011;64:71-7).

Dr. Cather noted that more studies are needed to assess the true impact of psoriasis on pregnancy.

She disclosed that she serves as a consultant to Abbott, Amgen, Centocor, and has received research grants from Amgen, Celgene, and Pfizer. SDEF and this news organization are owned by Elsevier.