Psoriasis

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

MIAMI BEACH – A diagnosis of pediatric psoriasis is a major event for a child and their family – especially given the long-term medical and psychosocial implications – so proceed cautiously, said Dr. Ronald C. Hansen.

"I am never in a big hurry to make the diagnosis of psoriasis if I am not sure. When you make the diagnosis, you are pretty much saying: ‘You are going to have some degree of psoriasis the rest of your life," Dr. Hansen said at the South Beach Symposium.

And, "I never ever underestimate the impact of psoriasis on the child’s life," he said. "I’ve had 5-year-olds already psychologically stricken."

Affected children – particularly those with more severe disease – will be self-conscious and avoid undressing before gym class or joining others to swim at a pool, said Dr. Hansen, chief of pediatric dermatology at Phoenix Children’s Hospital. "These kids end up loathing their bodies." Psoriasis often has long-term impacts on relationships and intimacy as well.

"The psychosocial impacts ... are immense," agreed session moderator Dr. Lawrence A. Schachner. Because of this, consider whether your patient needs psychosocial counseling when you diagnose psoriasis, added Dr. Schachner, who is director of pediatric dermatology at the University of Miami.

Pediatric psoriasis impacts the whole family. Counsel parents that psoriasis will require a long-term commitment to provide care for their child.

The onset of childhood psoriasis can occur at any age, even at birth. "It is genetically loaded," Dr. Hansen said.

For example, a child born to unaffected parents has about a 4% chance of developing psoriasis, he said. In contrast, a child born to one parent with psoriasis has a 28% likelihood of also developing psoriasis, and if both parents are affected, it jumps to 65%. The chances are even greater if the child has a sibling with psoriasis.

A clinical tip is to ask parents about a history of diaper dermatitis. In his experience, when Dr. Hansen suspects childhood psoriasis, he asks families about whether the child has had difficult diaper rashes. "The parents roll their eyes and say, ‘Yes, diaper rashes from hell.’ This is one of the things I hear routinely when I make the diagnosis in a 4-year-old."

Umbilical and scalp involvement often suggest psoriasis. Severe seborrheic dermatitis, for example, is another diagnostic clue. "We all know about the flaky, persistent scalp dermatitis, sometimes misdiagnosed as seborrheic dermatitis, but again it’s the seborrheic dermatitis from hell. It doesn’t respond to usual treatments," he said.

Even with a rash that looks like psoriasis, most children will have something else: seborrheic dermatitis, atopic dermatitis, or a candidal infection. "If it’s the first time I see this rash, I don’t make the diagnosis of psoriasis. ... Maybe about 20% of them will end up with psoriasis," Dr. Hansen said.

In contrast to adults with psoriasis, pediatric patients can present with prominent, full facial involvement. Flexural involvement is common in all ages, and the lesions can be thick and white or erythematous.

Be particularly thorough with your differential diagnosis of annular psoriasis. "The annular form can fool us. There are a lot of things that cause rings," Dr. Hansen said. A misdiagnosis of extensive tinea can occur, for example.

Some children with psoriasis can have extensive nail involvement. But "nail pits typify psoriasis. ... You can only use nail pits as a diagnostic [criterion] for psoriasis if the cuticle and proximal nail fold are intact," he said.

Pustular psoriasis is rare but important to diagnose in children, Dr. Hansen said. "These patients can be physically quite ill, and treatment has to be instituted right away."

Acute generalized pustular psoriasis is a severe form. Patients can present with fevers, polyarthritis, alopecia, cholestatic jaundice, acute respiratory distress syndrome, eye complications, conjunctivitis, and other adverse signs and comorbidities. "These kids tend to be medical emergencies," Dr. Hansen said. "Consider hospitalization if they have fever."

Many potential factors can elicit this condition. Acute generalized pustular psoriasis can be triggered by an upper respiratory infection or urinary tract infection. "Infections can open the door to anyone already predisposed to get psoriasis," Dr. Hansen said. Withdrawal from systemic or topical steroids and sunburn are other triggers. "Interestingly enough, the [tumor necrosis factor] antagonists which we use to treat psoriasis can also precipitate generalized pustular psoriasis. This confuses most people," he said.

Dr. Hansen disclosed that is a researcher for Novartis. Dr. Schachner disclosed that he is a consultant for Beiersdorf and a researcher/investigator for Astellas, Ferndale, Novartis, Organogenesis, and Stiefel. Both receive royalties from Elsevier, which also owns this news organization.

MIAMI BEACH – A diagnosis of pediatric psoriasis is a major event for a child and their family – especially given the long-term medical and psychosocial implications – so proceed cautiously, said Dr. Ronald C. Hansen.

"I am never in a big hurry to make the diagnosis of psoriasis if I am not sure. When you make the diagnosis, you are pretty much saying: ‘You are going to have some degree of psoriasis the rest of your life," Dr. Hansen said at the South Beach Symposium.

And, "I never ever underestimate the impact of psoriasis on the child’s life," he said. "I’ve had 5-year-olds already psychologically stricken."

Affected children – particularly those with more severe disease – will be self-conscious and avoid undressing before gym class or joining others to swim at a pool, said Dr. Hansen, chief of pediatric dermatology at Phoenix Children’s Hospital. "These kids end up loathing their bodies." Psoriasis often has long-term impacts on relationships and intimacy as well.

"The psychosocial impacts ... are immense," agreed session moderator Dr. Lawrence A. Schachner. Because of this, consider whether your patient needs psychosocial counseling when you diagnose psoriasis, added Dr. Schachner, who is director of pediatric dermatology at the University of Miami.

Pediatric psoriasis impacts the whole family. Counsel parents that psoriasis will require a long-term commitment to provide care for their child.

The onset of childhood psoriasis can occur at any age, even at birth. "It is genetically loaded," Dr. Hansen said.

For example, a child born to unaffected parents has about a 4% chance of developing psoriasis, he said. In contrast, a child born to one parent with psoriasis has a 28% likelihood of also developing psoriasis, and if both parents are affected, it jumps to 65%. The chances are even greater if the child has a sibling with psoriasis.

A clinical tip is to ask parents about a history of diaper dermatitis. In his experience, when Dr. Hansen suspects childhood psoriasis, he asks families about whether the child has had difficult diaper rashes. "The parents roll their eyes and say, ‘Yes, diaper rashes from hell.’ This is one of the things I hear routinely when I make the diagnosis in a 4-year-old."

Umbilical and scalp involvement often suggest psoriasis. Severe seborrheic dermatitis, for example, is another diagnostic clue. "We all know about the flaky, persistent scalp dermatitis, sometimes misdiagnosed as seborrheic dermatitis, but again it’s the seborrheic dermatitis from hell. It doesn’t respond to usual treatments," he said.

Even with a rash that looks like psoriasis, most children will have something else: seborrheic dermatitis, atopic dermatitis, or a candidal infection. "If it’s the first time I see this rash, I don’t make the diagnosis of psoriasis. ... Maybe about 20% of them will end up with psoriasis," Dr. Hansen said.

In contrast to adults with psoriasis, pediatric patients can present with prominent, full facial involvement. Flexural involvement is common in all ages, and the lesions can be thick and white or erythematous.

Be particularly thorough with your differential diagnosis of annular psoriasis. "The annular form can fool us. There are a lot of things that cause rings," Dr. Hansen said. A misdiagnosis of extensive tinea can occur, for example.

Some children with psoriasis can have extensive nail involvement. But "nail pits typify psoriasis. ... You can only use nail pits as a diagnostic [criterion] for psoriasis if the cuticle and proximal nail fold are intact," he said.

Pustular psoriasis is rare but important to diagnose in children, Dr. Hansen said. "These patients can be physically quite ill, and treatment has to be instituted right away."

Acute generalized pustular psoriasis is a severe form. Patients can present with fevers, polyarthritis, alopecia, cholestatic jaundice, acute respiratory distress syndrome, eye complications, conjunctivitis, and other adverse signs and comorbidities. "These kids tend to be medical emergencies," Dr. Hansen said. "Consider hospitalization if they have fever."

Many potential factors can elicit this condition. Acute generalized pustular psoriasis can be triggered by an upper respiratory infection or urinary tract infection. "Infections can open the door to anyone already predisposed to get psoriasis," Dr. Hansen said. Withdrawal from systemic or topical steroids and sunburn are other triggers. "Interestingly enough, the [tumor necrosis factor] antagonists which we use to treat psoriasis can also precipitate generalized pustular psoriasis. This confuses most people," he said.

Dr. Hansen disclosed that is a researcher for Novartis. Dr. Schachner disclosed that he is a consultant for Beiersdorf and a researcher/investigator for Astellas, Ferndale, Novartis, Organogenesis, and Stiefel. Both receive royalties from Elsevier, which also owns this news organization.

MIAMI BEACH – A diagnosis of pediatric psoriasis is a major event for a child and their family – especially given the long-term medical and psychosocial implications – so proceed cautiously, said Dr. Ronald C. Hansen.

"I am never in a big hurry to make the diagnosis of psoriasis if I am not sure. When you make the diagnosis, you are pretty much saying: ‘You are going to have some degree of psoriasis the rest of your life," Dr. Hansen said at the South Beach Symposium.

And, "I never ever underestimate the impact of psoriasis on the child’s life," he said. "I’ve had 5-year-olds already psychologically stricken."

Affected children – particularly those with more severe disease – will be self-conscious and avoid undressing before gym class or joining others to swim at a pool, said Dr. Hansen, chief of pediatric dermatology at Phoenix Children’s Hospital. "These kids end up loathing their bodies." Psoriasis often has long-term impacts on relationships and intimacy as well.

"The psychosocial impacts ... are immense," agreed session moderator Dr. Lawrence A. Schachner. Because of this, consider whether your patient needs psychosocial counseling when you diagnose psoriasis, added Dr. Schachner, who is director of pediatric dermatology at the University of Miami.

Pediatric psoriasis impacts the whole family. Counsel parents that psoriasis will require a long-term commitment to provide care for their child.

The onset of childhood psoriasis can occur at any age, even at birth. "It is genetically loaded," Dr. Hansen said.

For example, a child born to unaffected parents has about a 4% chance of developing psoriasis, he said. In contrast, a child born to one parent with psoriasis has a 28% likelihood of also developing psoriasis, and if both parents are affected, it jumps to 65%. The chances are even greater if the child has a sibling with psoriasis.

A clinical tip is to ask parents about a history of diaper dermatitis. In his experience, when Dr. Hansen suspects childhood psoriasis, he asks families about whether the child has had difficult diaper rashes. "The parents roll their eyes and say, ‘Yes, diaper rashes from hell.’ This is one of the things I hear routinely when I make the diagnosis in a 4-year-old."

Umbilical and scalp involvement often suggest psoriasis. Severe seborrheic dermatitis, for example, is another diagnostic clue. "We all know about the flaky, persistent scalp dermatitis, sometimes misdiagnosed as seborrheic dermatitis, but again it’s the seborrheic dermatitis from hell. It doesn’t respond to usual treatments," he said.

Even with a rash that looks like psoriasis, most children will have something else: seborrheic dermatitis, atopic dermatitis, or a candidal infection. "If it’s the first time I see this rash, I don’t make the diagnosis of psoriasis. ... Maybe about 20% of them will end up with psoriasis," Dr. Hansen said.

In contrast to adults with psoriasis, pediatric patients can present with prominent, full facial involvement. Flexural involvement is common in all ages, and the lesions can be thick and white or erythematous.

Be particularly thorough with your differential diagnosis of annular psoriasis. "The annular form can fool us. There are a lot of things that cause rings," Dr. Hansen said. A misdiagnosis of extensive tinea can occur, for example.

Some children with psoriasis can have extensive nail involvement. But "nail pits typify psoriasis. ... You can only use nail pits as a diagnostic [criterion] for psoriasis if the cuticle and proximal nail fold are intact," he said.

Pustular psoriasis is rare but important to diagnose in children, Dr. Hansen said. "These patients can be physically quite ill, and treatment has to be instituted right away."

Acute generalized pustular psoriasis is a severe form. Patients can present with fevers, polyarthritis, alopecia, cholestatic jaundice, acute respiratory distress syndrome, eye complications, conjunctivitis, and other adverse signs and comorbidities. "These kids tend to be medical emergencies," Dr. Hansen said. "Consider hospitalization if they have fever."

Many potential factors can elicit this condition. Acute generalized pustular psoriasis can be triggered by an upper respiratory infection or urinary tract infection. "Infections can open the door to anyone already predisposed to get psoriasis," Dr. Hansen said. Withdrawal from systemic or topical steroids and sunburn are other triggers. "Interestingly enough, the [tumor necrosis factor] antagonists which we use to treat psoriasis can also precipitate generalized pustular psoriasis. This confuses most people," he said.

Dr. Hansen disclosed that is a researcher for Novartis. Dr. Schachner disclosed that he is a consultant for Beiersdorf and a researcher/investigator for Astellas, Ferndale, Novartis, Organogenesis, and Stiefel. Both receive royalties from Elsevier, which also owns this news organization.

SAN DIEGO – A large study has determined that psoriasis is not an independent risk factor for ischemic heart disease, based on Framingham Risk Scores.

While previous studies have demonstrated that cardiac mortality is increased in patients with psoriasis, it is also known that people with the skin condition have a higher prevalence of smoking, alcohol consumption, obesity, diabetes, and dyslipidemia, researchers reported in a poster session at the annual meeting of the American Academy of Dermatology.

"Is this increase in ischemic heart disease due to traditional risk factors, or is psoriasis an additional independent risk factor?" wrote the investigators, who were led by Dr. Marian T. McEvoy, in the abstract.

They performed a population-based analysis of 1,338 adults with psoriasis who resided in Olmstead County, Minn., between 1998 and 2008 to evaluate the validity of the Framingham Risk Score (FRS) in predicting the incidence of ischemic heart disease in the study cohort. The FRS is a validated measure of standard ischemic heart disease risk factors.

Dr. McEvoy, a dermatologist at the Mayo Clinic in Rochester, Minn., and her associates compared the risk of cardiac death and myocardial infarction based on the FRS with the actual incidence of myocardial infarction and cardiac death in the study population, which was limited to patients older than age 30 but younger than age 80. They used Poisson regression models and standardized incidence ratios for statistical analysis.

The researchers reported that full Framingham risk factors were available for 974 of the 1,338 patients (73%). They predicted that the median 10-year risk of cardiac events based on the FRS was 3.8%, while the observed 10-year risk of cardiac events was 5.5%. However, there were 44 observed cardiac events compared with 47.7 FRS-predicted cardiac events, which translated into a standardized incidence ratio between the two groups of 0.9. Standardized incidence ratios also showed no statistically significant differences between the two groups when analyzed by gender, by age greater than 65 years, by age less than 65 years, and by whether patients were receiving systemic treatment or not.

"If psoriasis was an independent risk factor for ischemic heart disease, the observed incidence of cardiac events would have been in excess of predicted," the researchers wrote in their poster. "Since there was no statistical difference between actual and predicted events, psoriasis is not an independent risk factor for ischemic heart disease."

In a later interview, Dr. McEvoy acknowledged certain limitations of the study, including the fact that the small number of observed cardiac events (44) limited the statistical power of the study. "Since this is a retrospective study, we did not have a good tool to assess severity of psoriasis," she said. "We used surrogates based on therapy to identify those with ‘more severe disease.’ The Framingham Risk Score was valid for this group also."

The study was partially funded by a grant from Pfizer, and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project.

SAN DIEGO – A large study has determined that psoriasis is not an independent risk factor for ischemic heart disease, based on Framingham Risk Scores.

While previous studies have demonstrated that cardiac mortality is increased in patients with psoriasis, it is also known that people with the skin condition have a higher prevalence of smoking, alcohol consumption, obesity, diabetes, and dyslipidemia, researchers reported in a poster session at the annual meeting of the American Academy of Dermatology.

"Is this increase in ischemic heart disease due to traditional risk factors, or is psoriasis an additional independent risk factor?" wrote the investigators, who were led by Dr. Marian T. McEvoy, in the abstract.

They performed a population-based analysis of 1,338 adults with psoriasis who resided in Olmstead County, Minn., between 1998 and 2008 to evaluate the validity of the Framingham Risk Score (FRS) in predicting the incidence of ischemic heart disease in the study cohort. The FRS is a validated measure of standard ischemic heart disease risk factors.

Dr. McEvoy, a dermatologist at the Mayo Clinic in Rochester, Minn., and her associates compared the risk of cardiac death and myocardial infarction based on the FRS with the actual incidence of myocardial infarction and cardiac death in the study population, which was limited to patients older than age 30 but younger than age 80. They used Poisson regression models and standardized incidence ratios for statistical analysis.

The researchers reported that full Framingham risk factors were available for 974 of the 1,338 patients (73%). They predicted that the median 10-year risk of cardiac events based on the FRS was 3.8%, while the observed 10-year risk of cardiac events was 5.5%. However, there were 44 observed cardiac events compared with 47.7 FRS-predicted cardiac events, which translated into a standardized incidence ratio between the two groups of 0.9. Standardized incidence ratios also showed no statistically significant differences between the two groups when analyzed by gender, by age greater than 65 years, by age less than 65 years, and by whether patients were receiving systemic treatment or not.

"If psoriasis was an independent risk factor for ischemic heart disease, the observed incidence of cardiac events would have been in excess of predicted," the researchers wrote in their poster. "Since there was no statistical difference between actual and predicted events, psoriasis is not an independent risk factor for ischemic heart disease."

In a later interview, Dr. McEvoy acknowledged certain limitations of the study, including the fact that the small number of observed cardiac events (44) limited the statistical power of the study. "Since this is a retrospective study, we did not have a good tool to assess severity of psoriasis," she said. "We used surrogates based on therapy to identify those with ‘more severe disease.’ The Framingham Risk Score was valid for this group also."

The study was partially funded by a grant from Pfizer, and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project.

SAN DIEGO – A large study has determined that psoriasis is not an independent risk factor for ischemic heart disease, based on Framingham Risk Scores.

While previous studies have demonstrated that cardiac mortality is increased in patients with psoriasis, it is also known that people with the skin condition have a higher prevalence of smoking, alcohol consumption, obesity, diabetes, and dyslipidemia, researchers reported in a poster session at the annual meeting of the American Academy of Dermatology.

"Is this increase in ischemic heart disease due to traditional risk factors, or is psoriasis an additional independent risk factor?" wrote the investigators, who were led by Dr. Marian T. McEvoy, in the abstract.

They performed a population-based analysis of 1,338 adults with psoriasis who resided in Olmstead County, Minn., between 1998 and 2008 to evaluate the validity of the Framingham Risk Score (FRS) in predicting the incidence of ischemic heart disease in the study cohort. The FRS is a validated measure of standard ischemic heart disease risk factors.

Dr. McEvoy, a dermatologist at the Mayo Clinic in Rochester, Minn., and her associates compared the risk of cardiac death and myocardial infarction based on the FRS with the actual incidence of myocardial infarction and cardiac death in the study population, which was limited to patients older than age 30 but younger than age 80. They used Poisson regression models and standardized incidence ratios for statistical analysis.

The researchers reported that full Framingham risk factors were available for 974 of the 1,338 patients (73%). They predicted that the median 10-year risk of cardiac events based on the FRS was 3.8%, while the observed 10-year risk of cardiac events was 5.5%. However, there were 44 observed cardiac events compared with 47.7 FRS-predicted cardiac events, which translated into a standardized incidence ratio between the two groups of 0.9. Standardized incidence ratios also showed no statistically significant differences between the two groups when analyzed by gender, by age greater than 65 years, by age less than 65 years, and by whether patients were receiving systemic treatment or not.

"If psoriasis was an independent risk factor for ischemic heart disease, the observed incidence of cardiac events would have been in excess of predicted," the researchers wrote in their poster. "Since there was no statistical difference between actual and predicted events, psoriasis is not an independent risk factor for ischemic heart disease."

In a later interview, Dr. McEvoy acknowledged certain limitations of the study, including the fact that the small number of observed cardiac events (44) limited the statistical power of the study. "Since this is a retrospective study, we did not have a good tool to assess severity of psoriasis," she said. "We used surrogates based on therapy to identify those with ‘more severe disease.’ The Framingham Risk Score was valid for this group also."

The study was partially funded by a grant from Pfizer, and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project.

In this month's program, Dr. Daniel E. Furst delivers tips for differentiating arthritis types in psoriasis patients with joint pain.

Dr. Thomas E. Rohrer shares the unveiling of the AAD's new prevention program: SPOT Skin Cancer.

Then, Dr. Lawrence F. Eichenfield discusses the first-ever acne treatment guidelines for children.

Cosmetic counter host Dr. Lily Talakoub explains how to talk to patients about the potentially toxic chemicals in their makeup bag.

And finally, Dr. Alan Rockoff explains why his young grandson doesn't want to be a "lotion" doctor.

In this month's program, Dr. Daniel E. Furst delivers tips for differentiating arthritis types in psoriasis patients with joint pain.

Dr. Thomas E. Rohrer shares the unveiling of the AAD's new prevention program: SPOT Skin Cancer.

Then, Dr. Lawrence F. Eichenfield discusses the first-ever acne treatment guidelines for children.

Cosmetic counter host Dr. Lily Talakoub explains how to talk to patients about the potentially toxic chemicals in their makeup bag.

And finally, Dr. Alan Rockoff explains why his young grandson doesn't want to be a "lotion" doctor.

In this month's program, Dr. Daniel E. Furst delivers tips for differentiating arthritis types in psoriasis patients with joint pain.

Dr. Thomas E. Rohrer shares the unveiling of the AAD's new prevention program: SPOT Skin Cancer.

Then, Dr. Lawrence F. Eichenfield discusses the first-ever acne treatment guidelines for children.

Cosmetic counter host Dr. Lily Talakoub explains how to talk to patients about the potentially toxic chemicals in their makeup bag.

And finally, Dr. Alan Rockoff explains why his young grandson doesn't want to be a "lotion" doctor.

Provisional new classification criteria for Sjögren’s syndrome take into account the availability of new biologic treatment agents, rely solely on objective measures, and improve classification performance when compared with existing alternatives, according to the American College of Rheumatology.

The new criteria, which are the first to be endorsed by the ACR, target individuals with signs and symptoms suggestive of Sjögren’s syndrome and are based on expert opinion derived by analysis of data from the more than 1,300 patients in the SICCA (Sjögren’s International Collaborative Clinical Alliance) registry. They also differ from previous criteria in that only objective tests related to oral, ocular, and systemic manifestations of the syndrome are included.

This brings together three medical specialties – rheumatology, ophthalmology, and oral medicine – for the purpose of determining a patient’s disease status, and reinforces the importance of collaboration among these specialties when it comes to assessment and management of patients with Sjögren’s syndrome. It also protects patients by reducing the likelihood of misclassification, which could lead to unnecessary exposure to investigational drugs, according to Stephen C. Shiboski, Ph.D., of the University of California, San Francisco, and colleagues from the SICCA Research Groups, which authored the classification criteria.

Under the provisional guidelines, a classification as having Sjögren’s syndrome requires that a patient meet at least two of these three conditions:

• A blood test indicating the presence of anti–Sjögren’s syndrome antigen A and/or anti–Sjögren’s syndrome antigen B, or positive rheumatoid factor and antinuclear antibody titer of at least 1:320.

• An impaired ability to produce tears, as determined by an eye examination with an ocular staining score of 3 or greater.

• The presence of autoimmune impairment of salivary function, as determined by a focus score of 1 or more focus/4 mm² in labial salivary gland biopsy samples, the investigators said (Arthritis Care Res. 2012;64:475-87).

A high level of consensus was reached by the 20 members of the expert panel with respect to the use of the these objective measures, with 86% agreeing or strongly agreeing that meeting two of these three criteria should be required to classify Sjögren’s syndrome.

Preliminary validation of the classification criteria was based on comparison with the American-European Consensus Group criteria, which are likely the most frequently used criteria, and with cases and controls from external sources to the population used for criteria development. These comparisons showed high levels of sensitivity (96.3%) and specificity (83%) for the new criteria, which exceeded those of the alternative criteria, the investigators noted.

The findings are important, given the availability and development of new biologic agents for the treatment of Sjögren’s syndrome.

"Until recently, since few therapeutic agents were being considered in the systemic management of [Sjögren’s syndrome], the development of classification criteria was mainly for the purpose of epidemiologic studies to estimate the prevalence of the disease. However, the development of new biologic immunomodulating agents that are being considered in the treatment of [Sjögren’s syndrome] increases the need and importance of developing stringent classification criteria that can be used in the context of clinical trials," the investigators wrote, explaining that the consequences of misclassifying someone as having Sjögren’s syndrome would be serious, given the potentially toxic side effects of the biologic agents.

The results of the validation analyses performed in the development of these criteria indicate that they constitute a set of criteria that are stringent enough to be used for allowing entry into clinical trials, they said.

These new classification criteria have been quantitatively validated using patient data, and have been approved by the ACR board of directors, but have not yet undergone validation based on an external data set.

This work was supported by the National Institutes of Health, including the National Institute for Dental and Craniofacial Research, the National Eye Institute, and the Office of Research on Women’s Health. Three authors made disclosures, including Dr. F. Vivino, who has received consultant fees and/or honoraria from Daiichi-Sankyo and Parion Sciences; Dr. A. Wu, who owns stock and/or stock options in Isis Pharmaceuticals and Schering-Plough; and Dr. J. S. Greenspan, who has received consultant fees from GlaxoSmithKline.

Provisional new classification criteria for Sjögren’s syndrome take into account the availability of new biologic treatment agents, rely solely on objective measures, and improve classification performance when compared with existing alternatives, according to the American College of Rheumatology.

The new criteria, which are the first to be endorsed by the ACR, target individuals with signs and symptoms suggestive of Sjögren’s syndrome and are based on expert opinion derived by analysis of data from the more than 1,300 patients in the SICCA (Sjögren’s International Collaborative Clinical Alliance) registry. They also differ from previous criteria in that only objective tests related to oral, ocular, and systemic manifestations of the syndrome are included.

This brings together three medical specialties – rheumatology, ophthalmology, and oral medicine – for the purpose of determining a patient’s disease status, and reinforces the importance of collaboration among these specialties when it comes to assessment and management of patients with Sjögren’s syndrome. It also protects patients by reducing the likelihood of misclassification, which could lead to unnecessary exposure to investigational drugs, according to Stephen C. Shiboski, Ph.D., of the University of California, San Francisco, and colleagues from the SICCA Research Groups, which authored the classification criteria.

Under the provisional guidelines, a classification as having Sjögren’s syndrome requires that a patient meet at least two of these three conditions:

• A blood test indicating the presence of anti–Sjögren’s syndrome antigen A and/or anti–Sjögren’s syndrome antigen B, or positive rheumatoid factor and antinuclear antibody titer of at least 1:320.

• An impaired ability to produce tears, as determined by an eye examination with an ocular staining score of 3 or greater.

• The presence of autoimmune impairment of salivary function, as determined by a focus score of 1 or more focus/4 mm² in labial salivary gland biopsy samples, the investigators said (Arthritis Care Res. 2012;64:475-87).

A high level of consensus was reached by the 20 members of the expert panel with respect to the use of the these objective measures, with 86% agreeing or strongly agreeing that meeting two of these three criteria should be required to classify Sjögren’s syndrome.

Preliminary validation of the classification criteria was based on comparison with the American-European Consensus Group criteria, which are likely the most frequently used criteria, and with cases and controls from external sources to the population used for criteria development. These comparisons showed high levels of sensitivity (96.3%) and specificity (83%) for the new criteria, which exceeded those of the alternative criteria, the investigators noted.

The findings are important, given the availability and development of new biologic agents for the treatment of Sjögren’s syndrome.

"Until recently, since few therapeutic agents were being considered in the systemic management of [Sjögren’s syndrome], the development of classification criteria was mainly for the purpose of epidemiologic studies to estimate the prevalence of the disease. However, the development of new biologic immunomodulating agents that are being considered in the treatment of [Sjögren’s syndrome] increases the need and importance of developing stringent classification criteria that can be used in the context of clinical trials," the investigators wrote, explaining that the consequences of misclassifying someone as having Sjögren’s syndrome would be serious, given the potentially toxic side effects of the biologic agents.

The results of the validation analyses performed in the development of these criteria indicate that they constitute a set of criteria that are stringent enough to be used for allowing entry into clinical trials, they said.

These new classification criteria have been quantitatively validated using patient data, and have been approved by the ACR board of directors, but have not yet undergone validation based on an external data set.

This work was supported by the National Institutes of Health, including the National Institute for Dental and Craniofacial Research, the National Eye Institute, and the Office of Research on Women’s Health. Three authors made disclosures, including Dr. F. Vivino, who has received consultant fees and/or honoraria from Daiichi-Sankyo and Parion Sciences; Dr. A. Wu, who owns stock and/or stock options in Isis Pharmaceuticals and Schering-Plough; and Dr. J. S. Greenspan, who has received consultant fees from GlaxoSmithKline.

Provisional new classification criteria for Sjögren’s syndrome take into account the availability of new biologic treatment agents, rely solely on objective measures, and improve classification performance when compared with existing alternatives, according to the American College of Rheumatology.

The new criteria, which are the first to be endorsed by the ACR, target individuals with signs and symptoms suggestive of Sjögren’s syndrome and are based on expert opinion derived by analysis of data from the more than 1,300 patients in the SICCA (Sjögren’s International Collaborative Clinical Alliance) registry. They also differ from previous criteria in that only objective tests related to oral, ocular, and systemic manifestations of the syndrome are included.

This brings together three medical specialties – rheumatology, ophthalmology, and oral medicine – for the purpose of determining a patient’s disease status, and reinforces the importance of collaboration among these specialties when it comes to assessment and management of patients with Sjögren’s syndrome. It also protects patients by reducing the likelihood of misclassification, which could lead to unnecessary exposure to investigational drugs, according to Stephen C. Shiboski, Ph.D., of the University of California, San Francisco, and colleagues from the SICCA Research Groups, which authored the classification criteria.

Under the provisional guidelines, a classification as having Sjögren’s syndrome requires that a patient meet at least two of these three conditions:

• A blood test indicating the presence of anti–Sjögren’s syndrome antigen A and/or anti–Sjögren’s syndrome antigen B, or positive rheumatoid factor and antinuclear antibody titer of at least 1:320.

• An impaired ability to produce tears, as determined by an eye examination with an ocular staining score of 3 or greater.

• The presence of autoimmune impairment of salivary function, as determined by a focus score of 1 or more focus/4 mm² in labial salivary gland biopsy samples, the investigators said (Arthritis Care Res. 2012;64:475-87).

A high level of consensus was reached by the 20 members of the expert panel with respect to the use of the these objective measures, with 86% agreeing or strongly agreeing that meeting two of these three criteria should be required to classify Sjögren’s syndrome.

Preliminary validation of the classification criteria was based on comparison with the American-European Consensus Group criteria, which are likely the most frequently used criteria, and with cases and controls from external sources to the population used for criteria development. These comparisons showed high levels of sensitivity (96.3%) and specificity (83%) for the new criteria, which exceeded those of the alternative criteria, the investigators noted.

The findings are important, given the availability and development of new biologic agents for the treatment of Sjögren’s syndrome.

"Until recently, since few therapeutic agents were being considered in the systemic management of [Sjögren’s syndrome], the development of classification criteria was mainly for the purpose of epidemiologic studies to estimate the prevalence of the disease. However, the development of new biologic immunomodulating agents that are being considered in the treatment of [Sjögren’s syndrome] increases the need and importance of developing stringent classification criteria that can be used in the context of clinical trials," the investigators wrote, explaining that the consequences of misclassifying someone as having Sjögren’s syndrome would be serious, given the potentially toxic side effects of the biologic agents.

The results of the validation analyses performed in the development of these criteria indicate that they constitute a set of criteria that are stringent enough to be used for allowing entry into clinical trials, they said.

These new classification criteria have been quantitatively validated using patient data, and have been approved by the ACR board of directors, but have not yet undergone validation based on an external data set.

This work was supported by the National Institutes of Health, including the National Institute for Dental and Craniofacial Research, the National Eye Institute, and the Office of Research on Women’s Health. Three authors made disclosures, including Dr. F. Vivino, who has received consultant fees and/or honoraria from Daiichi-Sankyo and Parion Sciences; Dr. A. Wu, who owns stock and/or stock options in Isis Pharmaceuticals and Schering-Plough; and Dr. J. S. Greenspan, who has received consultant fees from GlaxoSmithKline.

SAN DIEGO – While it’s well known that sarcoidosis commonly affects pulmonary function, it’s perhaps less known that the disorder can be detrimental to cardiac function in approximately 5% of cases.

"A common way that patients present with cardiac sarcoidosis is with sudden cardiac death," Dr. Misha Rosenbach said at the annual meeting of the American Academy of Dermatology. "This is a terrible way to present to your doctor with a problem."

A multisystem disorder of unknown cause, sarcoidosis commonly affects young and middle-aged adults and frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, and ocular and skin lesions. Other organs may be involved. The diagnosis is established when clinicoradiologic findings are supported by histologic evidence of noncaseating epithelioid cell granulomas.

"Sarcoidosis is primarily a pulmonary disease, but patients can also present with profound systemic symptoms," said Dr. Rosenbach of the departments of dermatology and internal medicine at the University of Pennsylvania, Philadelphia. "When you’re evaluating a patient with cutaneous sarcoidosis, and making a diagnosis of granulomatous disease of the skin, and looking for extracutaneous involvement, it’s important to know what else can be affected."

Although pulmonary function is affected in more than 90% of cases, other commonly affected sites include the eyes (25%-50% of cases), lymph nodes (about 33% of cases), musculoskeletal system (25%-40% of cases), endocrine system (10%-25% of cases), and liver (20%-50% of cases). The initial evaluation should consist of history and physical exam; chest x-ray; pulmonary function tests (including carbon monoxide diffusing capacity); ophthalmologic examination; complete blood count and serum chemistries (including calcium); urinalysis; EKG (plus additional testing if there is a history of palpitations); tuberculin skin test (TST) or interferon (IFN)–gamma release assay; and thyroid and vitamin D testing.

Images courtesy Dr. Misha Rosenbach

"Patients with sarcoidosis often have low levels of 25-hydroxyvitamin D, but elevated levels of 1,25-dihydroxyvitamin D₃," Dr. Rosenbach said. "Inappropriate supplementation can lead to hypercalcemia."

For latent tuberculosis testing, he pointed out that the IFN-gamma release assay (IGRA) is thought to be more accurate than the TST. "IGRA significantly reduces false-positive results" in bacille Calmette-Guérin–vaccinated patients, said Dr. Rosenbach, who is also director of the cutaneous sarcoidosis clinic at the University of Pennsylvania. "Cost-benefit analyses suggest that IGRA [is] cost equivalent to TST, and the Centers for Disease Control and Prevention recommends that IGRA may be used in all circumstances in which the TST is currently used. However, both TST and IGRA have decreased responsiveness and lower sensitivity in patients with impaired immune systems."

In terms of the impact of sarcoidosis on the thyroid gland, a recent analysis of a large database in the United Kingdom found that hyper- and hypothyroidism were twice as common in patients with sarcoidosis, compared with a control population (Postgrad. Med. J. 2009;85:233-7).

A more recent study of 50 patients with cutaneous sarcoidosis conducted by Dr. Rosenbach and his colleagues found that 25% of patients had abnormal thyroid laboratory test results (J. Am. Acad. Dermatol. 2012;66:167-8).

The precise association between sarcoidosis and malignancy remains unclear, he said, but the best available studies suggest that the incidence of lymphoproliferative disorder may be increased in patients with sarcoidosis. Other granulomatous dermatitides may be associated with hematologic abnormalities. Authors of one review found that granulomatous dermatitides may be the first sign of underlying myelodysplastic syndrome (MDS), and recommended that clinicians consider looking for underlying MDS in patients with unexplained or atypical granulomatous skin eruptions (Arch. Dermatol. 2011;147:331-5).

Images courtesy Dr. Misha Rosenbach

A common stepwise approach for treating patients, Dr. Rosenbach said, begins with skin-directed therapies in the form of steroids or injections. The second step involves the use of antimalarials and tetracycline-class antibiotics; the third step involves methotrexate and/or prednisone, and the fourth step involves consideration for treatment with infliximab or adalimumab. "At this point, etanercept should probably not be used," Dr. Rosenbach said. "It appears to be less effective, and in a few reports has been associated with worsening of disease."

The data are strongest for infliximab, he said, at a recommended dosage of 5 mg/kg at 0, 2, and 6 weeks, and then with maintenance therapy every 6-8 weeks. Adalimumab appeared to work best at 40 mg every week, he said, "but the addition of low-dose methotrexate is sometimes necessary to either regimen."

Dr. Rosenbach disclosed that he was an investigator for a clinical trial sponsored by Centocor and Johnson & Johnson to investigate biologics for chronic/refractory sarcoidosis.

SAN DIEGO – While it’s well known that sarcoidosis commonly affects pulmonary function, it’s perhaps less known that the disorder can be detrimental to cardiac function in approximately 5% of cases.

"A common way that patients present with cardiac sarcoidosis is with sudden cardiac death," Dr. Misha Rosenbach said at the annual meeting of the American Academy of Dermatology. "This is a terrible way to present to your doctor with a problem."

A multisystem disorder of unknown cause, sarcoidosis commonly affects young and middle-aged adults and frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, and ocular and skin lesions. Other organs may be involved. The diagnosis is established when clinicoradiologic findings are supported by histologic evidence of noncaseating epithelioid cell granulomas.

"Sarcoidosis is primarily a pulmonary disease, but patients can also present with profound systemic symptoms," said Dr. Rosenbach of the departments of dermatology and internal medicine at the University of Pennsylvania, Philadelphia. "When you’re evaluating a patient with cutaneous sarcoidosis, and making a diagnosis of granulomatous disease of the skin, and looking for extracutaneous involvement, it’s important to know what else can be affected."

Although pulmonary function is affected in more than 90% of cases, other commonly affected sites include the eyes (25%-50% of cases), lymph nodes (about 33% of cases), musculoskeletal system (25%-40% of cases), endocrine system (10%-25% of cases), and liver (20%-50% of cases). The initial evaluation should consist of history and physical exam; chest x-ray; pulmonary function tests (including carbon monoxide diffusing capacity); ophthalmologic examination; complete blood count and serum chemistries (including calcium); urinalysis; EKG (plus additional testing if there is a history of palpitations); tuberculin skin test (TST) or interferon (IFN)–gamma release assay; and thyroid and vitamin D testing.

Images courtesy Dr. Misha Rosenbach

"Patients with sarcoidosis often have low levels of 25-hydroxyvitamin D, but elevated levels of 1,25-dihydroxyvitamin D₃," Dr. Rosenbach said. "Inappropriate supplementation can lead to hypercalcemia."

For latent tuberculosis testing, he pointed out that the IFN-gamma release assay (IGRA) is thought to be more accurate than the TST. "IGRA significantly reduces false-positive results" in bacille Calmette-Guérin–vaccinated patients, said Dr. Rosenbach, who is also director of the cutaneous sarcoidosis clinic at the University of Pennsylvania. "Cost-benefit analyses suggest that IGRA [is] cost equivalent to TST, and the Centers for Disease Control and Prevention recommends that IGRA may be used in all circumstances in which the TST is currently used. However, both TST and IGRA have decreased responsiveness and lower sensitivity in patients with impaired immune systems."

In terms of the impact of sarcoidosis on the thyroid gland, a recent analysis of a large database in the United Kingdom found that hyper- and hypothyroidism were twice as common in patients with sarcoidosis, compared with a control population (Postgrad. Med. J. 2009;85:233-7).

A more recent study of 50 patients with cutaneous sarcoidosis conducted by Dr. Rosenbach and his colleagues found that 25% of patients had abnormal thyroid laboratory test results (J. Am. Acad. Dermatol. 2012;66:167-8).

The precise association between sarcoidosis and malignancy remains unclear, he said, but the best available studies suggest that the incidence of lymphoproliferative disorder may be increased in patients with sarcoidosis. Other granulomatous dermatitides may be associated with hematologic abnormalities. Authors of one review found that granulomatous dermatitides may be the first sign of underlying myelodysplastic syndrome (MDS), and recommended that clinicians consider looking for underlying MDS in patients with unexplained or atypical granulomatous skin eruptions (Arch. Dermatol. 2011;147:331-5).

Images courtesy Dr. Misha Rosenbach

A common stepwise approach for treating patients, Dr. Rosenbach said, begins with skin-directed therapies in the form of steroids or injections. The second step involves the use of antimalarials and tetracycline-class antibiotics; the third step involves methotrexate and/or prednisone, and the fourth step involves consideration for treatment with infliximab or adalimumab. "At this point, etanercept should probably not be used," Dr. Rosenbach said. "It appears to be less effective, and in a few reports has been associated with worsening of disease."

The data are strongest for infliximab, he said, at a recommended dosage of 5 mg/kg at 0, 2, and 6 weeks, and then with maintenance therapy every 6-8 weeks. Adalimumab appeared to work best at 40 mg every week, he said, "but the addition of low-dose methotrexate is sometimes necessary to either regimen."

Dr. Rosenbach disclosed that he was an investigator for a clinical trial sponsored by Centocor and Johnson & Johnson to investigate biologics for chronic/refractory sarcoidosis.

SAN DIEGO – While it’s well known that sarcoidosis commonly affects pulmonary function, it’s perhaps less known that the disorder can be detrimental to cardiac function in approximately 5% of cases.

"A common way that patients present with cardiac sarcoidosis is with sudden cardiac death," Dr. Misha Rosenbach said at the annual meeting of the American Academy of Dermatology. "This is a terrible way to present to your doctor with a problem."

A multisystem disorder of unknown cause, sarcoidosis commonly affects young and middle-aged adults and frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, and ocular and skin lesions. Other organs may be involved. The diagnosis is established when clinicoradiologic findings are supported by histologic evidence of noncaseating epithelioid cell granulomas.

"Sarcoidosis is primarily a pulmonary disease, but patients can also present with profound systemic symptoms," said Dr. Rosenbach of the departments of dermatology and internal medicine at the University of Pennsylvania, Philadelphia. "When you’re evaluating a patient with cutaneous sarcoidosis, and making a diagnosis of granulomatous disease of the skin, and looking for extracutaneous involvement, it’s important to know what else can be affected."

Although pulmonary function is affected in more than 90% of cases, other commonly affected sites include the eyes (25%-50% of cases), lymph nodes (about 33% of cases), musculoskeletal system (25%-40% of cases), endocrine system (10%-25% of cases), and liver (20%-50% of cases). The initial evaluation should consist of history and physical exam; chest x-ray; pulmonary function tests (including carbon monoxide diffusing capacity); ophthalmologic examination; complete blood count and serum chemistries (including calcium); urinalysis; EKG (plus additional testing if there is a history of palpitations); tuberculin skin test (TST) or interferon (IFN)–gamma release assay; and thyroid and vitamin D testing.

Images courtesy Dr. Misha Rosenbach

"Patients with sarcoidosis often have low levels of 25-hydroxyvitamin D, but elevated levels of 1,25-dihydroxyvitamin D₃," Dr. Rosenbach said. "Inappropriate supplementation can lead to hypercalcemia."

For latent tuberculosis testing, he pointed out that the IFN-gamma release assay (IGRA) is thought to be more accurate than the TST. "IGRA significantly reduces false-positive results" in bacille Calmette-Guérin–vaccinated patients, said Dr. Rosenbach, who is also director of the cutaneous sarcoidosis clinic at the University of Pennsylvania. "Cost-benefit analyses suggest that IGRA [is] cost equivalent to TST, and the Centers for Disease Control and Prevention recommends that IGRA may be used in all circumstances in which the TST is currently used. However, both TST and IGRA have decreased responsiveness and lower sensitivity in patients with impaired immune systems."

In terms of the impact of sarcoidosis on the thyroid gland, a recent analysis of a large database in the United Kingdom found that hyper- and hypothyroidism were twice as common in patients with sarcoidosis, compared with a control population (Postgrad. Med. J. 2009;85:233-7).

A more recent study of 50 patients with cutaneous sarcoidosis conducted by Dr. Rosenbach and his colleagues found that 25% of patients had abnormal thyroid laboratory test results (J. Am. Acad. Dermatol. 2012;66:167-8).

The precise association between sarcoidosis and malignancy remains unclear, he said, but the best available studies suggest that the incidence of lymphoproliferative disorder may be increased in patients with sarcoidosis. Other granulomatous dermatitides may be associated with hematologic abnormalities. Authors of one review found that granulomatous dermatitides may be the first sign of underlying myelodysplastic syndrome (MDS), and recommended that clinicians consider looking for underlying MDS in patients with unexplained or atypical granulomatous skin eruptions (Arch. Dermatol. 2011;147:331-5).

Images courtesy Dr. Misha Rosenbach

A common stepwise approach for treating patients, Dr. Rosenbach said, begins with skin-directed therapies in the form of steroids or injections. The second step involves the use of antimalarials and tetracycline-class antibiotics; the third step involves methotrexate and/or prednisone, and the fourth step involves consideration for treatment with infliximab or adalimumab. "At this point, etanercept should probably not be used," Dr. Rosenbach said. "It appears to be less effective, and in a few reports has been associated with worsening of disease."

The data are strongest for infliximab, he said, at a recommended dosage of 5 mg/kg at 0, 2, and 6 weeks, and then with maintenance therapy every 6-8 weeks. Adalimumab appeared to work best at 40 mg every week, he said, "but the addition of low-dose methotrexate is sometimes necessary to either regimen."

Dr. Rosenbach disclosed that he was an investigator for a clinical trial sponsored by Centocor and Johnson & Johnson to investigate biologics for chronic/refractory sarcoidosis.

Two monoclonal antibodies targeting interleukin-17 proved effective and safe for moderate to severe plaque psoriasis, according to the results of two phase II clinical trials reported in the March 29 issue of the New England Journal of Medicine.

Both agents had a rapid onset of action and improved scores on the psoriasis area and severity (PASI) index, as well as on measures of dermatology-related quality of life and overall well-being, compared with placebo. Both agents also showed increasing efficacy at higher doses, indicating a dose-response effect, according to the industry-sponsored studies.

Brodalumab

In the first study, researchers assessed brodalumab (AMG 827), a human anti-interleukin-17RA monoclonal antibody that antagonizes the interleukin-17 pathway, in 198 patients at 23 international sites.

The study patients were randomly assigned to receive 70 mg, 140 mg, or 210 mg of brodalumab (at weeks 1, 2, 4, 6, 8, and 10), 280 mg of brodalumab monthly, or placebo injections. A subgroup of 20 patients also underwent skin biopsy at baseline and at week 12, reported Dr. Kim A. Papp of Probity Medical Research, Waterloo, Ont., and his associates.

The mean patient age was 43 years, and the mean duration of psoriasis was 19 years. Most patients had previously received topical and systemic treatments, including phototherapy, and 35% had previously received biologic therapy.

The primary efficacy outcome – percentage improvement in PASI score at week 12 – was significantly greater in every brodalumab group than in the placebo group. Mean improvements were 45% with 70 mg, 85.9% with 140 mg, 86.3% with 210 mg, and 76% with 280 mg, and 16% with placebo.

"Similarly, a significantly higher percentage of patients in the brodalumab groups than in the placebo group [was] assessed as being clear of psoriasis (score of 0 on the physician’s global assessment) or as having minimal disease (score of 1) at week 12," Dr. Papp and his colleagues wrote (N. Engl. J. Med. 2012;366:1181-9)

In addition, the extent of the affected body-surface area was significantly smaller with active treatment than with placebo. Scores on the Dermatology Life Quality Index (DLQI) were significantly lower in the brodalumab groups, indicating that psoriasis had less of an impact on health-related quality of life. And scores on both physical and mental components of the SF-36 were significantly higher, indicating improved well-being, with brodalumab.

Among study patients who underwent skin biopsy, keratin 16 staining of the upper epidermis was reduced, and epidermal thickness and CD3 counts were decreased, at all doses of brodalumab except 70 mg. "This finding indicates a reversal of regenerative epidermal maturation, which is the essential pathological characteristic of psoriasis that causes epidermal hyperplasia and abnormal differentiation, with scaling and thickness as the clinical correlates," Dr. Papp and his associates noted.

At 16-week follow-up, which was 6-8 weeks after the final dose of brodalumab, PASI scores showed a diminished drug effect but were still better than those at baseline.

There were three serious adverse events, only one of which was related to the study drug. This was an asymptomatic case of grade 3 neutropenia, which resolved when the study drug was discontinued. A less serious case of neutropenia developed in another patient.

Ixekizumab

The second study assessed ixekizumab (LY2439821), a humanized IgG4 monoclonal antibody that neutralizes interleukin-17, in 142 patients with moderate to severe plaque psoriasis. The study patients were randomly assigned to receive subcutaneous injections of placebo or 10 mg, 25 mg, 75 mg, or 150 mg of ixekizumab at baseline and at 2, 4, 8, 12, and 16 weeks, reported Dr. Craig Leonardi of the department of dermatology, St. Louis University, and his associates.

The primary efficacy end point was the proportion of patients who achieved at least a 75% improvement in PASI score at 12 weeks. Significantly more patients at all ixekizumab doses except 10 mg achieved this benchmark (76.7%-82.8%), compared with placebo (7.7%).

In addition, significantly more patients (approximately 40%) in the higher-dose groups achieved a 100% improvement in PASI scores, indicating complete clearance of psoriasis, than in the placebo group. And significantly more patients receiving active treatment received physician’s global assessment scores of 0, indicating complete clearance, or 1, indicating minimal disease.

As with brodalumab, the beneficial effect of ixekizumab was evident as early as 1 week into treatment. The drug also significantly improved DLQI scores and decreased the severity of itching, Dr. Leonardi and his colleagues reported (New Engl. J. Med. 2012;366:1190-9).

Of note, ixekizumab was significantly more effective than placebo in patients who had psoriasis in difficult to treat areas such as the scalp and nails.

There were no serious adverse events. Two patients developed grade 2 neutropenia. Two patients showed elevations in liver enzymes that subsided when the drug was discontinued.

Both groups of investigators said their findings demonstrate that interleukin-17 is an appropriate target for psoriasis treatment. They also noted that the phase-II studies were too small and too brief to assess these agents’ effects on the risk of infection and cardiovascular events, and noted that further, longer-term studies of safety and efficacy are needed.

Even though there were few adverse effects in these two clinical trials and few patients withdrew from the studies, "a 12-week follow-up period is too short to assess the safety of treatments targeting interleukin-17," said Ari Waisman, Ph.D., in remarks taken from his editorial accompanying the reports on brodalumab and ixekizumab (N. Engl. J. Med. 2012;366:1251-2).

Despite the patients’ marked improvements with both brodalumab and ixekizumab, "future trials involving larger numbers of patients treated and followed for a much longer period of time will be needed," Dr. Waisman of the Institute for Molecular Medicine at Johannes-Gutenberg University of Mainz (Germany) said.

Dr. Papp’s study was funded by Amgen; Dr. Papp and his associates reported ties to numerous industry sources. Dr. Leonardi’s study was funded by Eli Lilly; Dr. Leonardi reported ties to Abbott, Amgen, Celgene, Centocor, Eli Lilly, Pfizer, Galderma, Incyte, Maruho, Schering-Plough, Sirtris, Stiefel, Novartis, Novo Nordisk, Vascular Biogenics, and Wyeth. Dr. Waisman reported ties to Teva, Phenex, and GlaxoSmithKline.

Two monoclonal antibodies targeting interleukin-17 proved effective and safe for moderate to severe plaque psoriasis, according to the results of two phase II clinical trials reported in the March 29 issue of the New England Journal of Medicine.

Both agents had a rapid onset of action and improved scores on the psoriasis area and severity (PASI) index, as well as on measures of dermatology-related quality of life and overall well-being, compared with placebo. Both agents also showed increasing efficacy at higher doses, indicating a dose-response effect, according to the industry-sponsored studies.

Brodalumab

In the first study, researchers assessed brodalumab (AMG 827), a human anti-interleukin-17RA monoclonal antibody that antagonizes the interleukin-17 pathway, in 198 patients at 23 international sites.

The study patients were randomly assigned to receive 70 mg, 140 mg, or 210 mg of brodalumab (at weeks 1, 2, 4, 6, 8, and 10), 280 mg of brodalumab monthly, or placebo injections. A subgroup of 20 patients also underwent skin biopsy at baseline and at week 12, reported Dr. Kim A. Papp of Probity Medical Research, Waterloo, Ont., and his associates.

The mean patient age was 43 years, and the mean duration of psoriasis was 19 years. Most patients had previously received topical and systemic treatments, including phototherapy, and 35% had previously received biologic therapy.

The primary efficacy outcome – percentage improvement in PASI score at week 12 – was significantly greater in every brodalumab group than in the placebo group. Mean improvements were 45% with 70 mg, 85.9% with 140 mg, 86.3% with 210 mg, and 76% with 280 mg, and 16% with placebo.

"Similarly, a significantly higher percentage of patients in the brodalumab groups than in the placebo group [was] assessed as being clear of psoriasis (score of 0 on the physician’s global assessment) or as having minimal disease (score of 1) at week 12," Dr. Papp and his colleagues wrote (N. Engl. J. Med. 2012;366:1181-9)

In addition, the extent of the affected body-surface area was significantly smaller with active treatment than with placebo. Scores on the Dermatology Life Quality Index (DLQI) were significantly lower in the brodalumab groups, indicating that psoriasis had less of an impact on health-related quality of life. And scores on both physical and mental components of the SF-36 were significantly higher, indicating improved well-being, with brodalumab.

Among study patients who underwent skin biopsy, keratin 16 staining of the upper epidermis was reduced, and epidermal thickness and CD3 counts were decreased, at all doses of brodalumab except 70 mg. "This finding indicates a reversal of regenerative epidermal maturation, which is the essential pathological characteristic of psoriasis that causes epidermal hyperplasia and abnormal differentiation, with scaling and thickness as the clinical correlates," Dr. Papp and his associates noted.

At 16-week follow-up, which was 6-8 weeks after the final dose of brodalumab, PASI scores showed a diminished drug effect but were still better than those at baseline.

There were three serious adverse events, only one of which was related to the study drug. This was an asymptomatic case of grade 3 neutropenia, which resolved when the study drug was discontinued. A less serious case of neutropenia developed in another patient.

Ixekizumab

The second study assessed ixekizumab (LY2439821), a humanized IgG4 monoclonal antibody that neutralizes interleukin-17, in 142 patients with moderate to severe plaque psoriasis. The study patients were randomly assigned to receive subcutaneous injections of placebo or 10 mg, 25 mg, 75 mg, or 150 mg of ixekizumab at baseline and at 2, 4, 8, 12, and 16 weeks, reported Dr. Craig Leonardi of the department of dermatology, St. Louis University, and his associates.

The primary efficacy end point was the proportion of patients who achieved at least a 75% improvement in PASI score at 12 weeks. Significantly more patients at all ixekizumab doses except 10 mg achieved this benchmark (76.7%-82.8%), compared with placebo (7.7%).

In addition, significantly more patients (approximately 40%) in the higher-dose groups achieved a 100% improvement in PASI scores, indicating complete clearance of psoriasis, than in the placebo group. And significantly more patients receiving active treatment received physician’s global assessment scores of 0, indicating complete clearance, or 1, indicating minimal disease.

As with brodalumab, the beneficial effect of ixekizumab was evident as early as 1 week into treatment. The drug also significantly improved DLQI scores and decreased the severity of itching, Dr. Leonardi and his colleagues reported (New Engl. J. Med. 2012;366:1190-9).

Of note, ixekizumab was significantly more effective than placebo in patients who had psoriasis in difficult to treat areas such as the scalp and nails.

There were no serious adverse events. Two patients developed grade 2 neutropenia. Two patients showed elevations in liver enzymes that subsided when the drug was discontinued.

Both groups of investigators said their findings demonstrate that interleukin-17 is an appropriate target for psoriasis treatment. They also noted that the phase-II studies were too small and too brief to assess these agents’ effects on the risk of infection and cardiovascular events, and noted that further, longer-term studies of safety and efficacy are needed.

Even though there were few adverse effects in these two clinical trials and few patients withdrew from the studies, "a 12-week follow-up period is too short to assess the safety of treatments targeting interleukin-17," said Ari Waisman, Ph.D., in remarks taken from his editorial accompanying the reports on brodalumab and ixekizumab (N. Engl. J. Med. 2012;366:1251-2).

Despite the patients’ marked improvements with both brodalumab and ixekizumab, "future trials involving larger numbers of patients treated and followed for a much longer period of time will be needed," Dr. Waisman of the Institute for Molecular Medicine at Johannes-Gutenberg University of Mainz (Germany) said.

Dr. Papp’s study was funded by Amgen; Dr. Papp and his associates reported ties to numerous industry sources. Dr. Leonardi’s study was funded by Eli Lilly; Dr. Leonardi reported ties to Abbott, Amgen, Celgene, Centocor, Eli Lilly, Pfizer, Galderma, Incyte, Maruho, Schering-Plough, Sirtris, Stiefel, Novartis, Novo Nordisk, Vascular Biogenics, and Wyeth. Dr. Waisman reported ties to Teva, Phenex, and GlaxoSmithKline.

Two monoclonal antibodies targeting interleukin-17 proved effective and safe for moderate to severe plaque psoriasis, according to the results of two phase II clinical trials reported in the March 29 issue of the New England Journal of Medicine.

Both agents had a rapid onset of action and improved scores on the psoriasis area and severity (PASI) index, as well as on measures of dermatology-related quality of life and overall well-being, compared with placebo. Both agents also showed increasing efficacy at higher doses, indicating a dose-response effect, according to the industry-sponsored studies.

Brodalumab

In the first study, researchers assessed brodalumab (AMG 827), a human anti-interleukin-17RA monoclonal antibody that antagonizes the interleukin-17 pathway, in 198 patients at 23 international sites.

The study patients were randomly assigned to receive 70 mg, 140 mg, or 210 mg of brodalumab (at weeks 1, 2, 4, 6, 8, and 10), 280 mg of brodalumab monthly, or placebo injections. A subgroup of 20 patients also underwent skin biopsy at baseline and at week 12, reported Dr. Kim A. Papp of Probity Medical Research, Waterloo, Ont., and his associates.

The mean patient age was 43 years, and the mean duration of psoriasis was 19 years. Most patients had previously received topical and systemic treatments, including phototherapy, and 35% had previously received biologic therapy.

The primary efficacy outcome – percentage improvement in PASI score at week 12 – was significantly greater in every brodalumab group than in the placebo group. Mean improvements were 45% with 70 mg, 85.9% with 140 mg, 86.3% with 210 mg, and 76% with 280 mg, and 16% with placebo.

"Similarly, a significantly higher percentage of patients in the brodalumab groups than in the placebo group [was] assessed as being clear of psoriasis (score of 0 on the physician’s global assessment) or as having minimal disease (score of 1) at week 12," Dr. Papp and his colleagues wrote (N. Engl. J. Med. 2012;366:1181-9)

In addition, the extent of the affected body-surface area was significantly smaller with active treatment than with placebo. Scores on the Dermatology Life Quality Index (DLQI) were significantly lower in the brodalumab groups, indicating that psoriasis had less of an impact on health-related quality of life. And scores on both physical and mental components of the SF-36 were significantly higher, indicating improved well-being, with brodalumab.

Among study patients who underwent skin biopsy, keratin 16 staining of the upper epidermis was reduced, and epidermal thickness and CD3 counts were decreased, at all doses of brodalumab except 70 mg. "This finding indicates a reversal of regenerative epidermal maturation, which is the essential pathological characteristic of psoriasis that causes epidermal hyperplasia and abnormal differentiation, with scaling and thickness as the clinical correlates," Dr. Papp and his associates noted.

At 16-week follow-up, which was 6-8 weeks after the final dose of brodalumab, PASI scores showed a diminished drug effect but were still better than those at baseline.

There were three serious adverse events, only one of which was related to the study drug. This was an asymptomatic case of grade 3 neutropenia, which resolved when the study drug was discontinued. A less serious case of neutropenia developed in another patient.

Ixekizumab

The second study assessed ixekizumab (LY2439821), a humanized IgG4 monoclonal antibody that neutralizes interleukin-17, in 142 patients with moderate to severe plaque psoriasis. The study patients were randomly assigned to receive subcutaneous injections of placebo or 10 mg, 25 mg, 75 mg, or 150 mg of ixekizumab at baseline and at 2, 4, 8, 12, and 16 weeks, reported Dr. Craig Leonardi of the department of dermatology, St. Louis University, and his associates.

The primary efficacy end point was the proportion of patients who achieved at least a 75% improvement in PASI score at 12 weeks. Significantly more patients at all ixekizumab doses except 10 mg achieved this benchmark (76.7%-82.8%), compared with placebo (7.7%).

In addition, significantly more patients (approximately 40%) in the higher-dose groups achieved a 100% improvement in PASI scores, indicating complete clearance of psoriasis, than in the placebo group. And significantly more patients receiving active treatment received physician’s global assessment scores of 0, indicating complete clearance, or 1, indicating minimal disease.

As with brodalumab, the beneficial effect of ixekizumab was evident as early as 1 week into treatment. The drug also significantly improved DLQI scores and decreased the severity of itching, Dr. Leonardi and his colleagues reported (New Engl. J. Med. 2012;366:1190-9).

Of note, ixekizumab was significantly more effective than placebo in patients who had psoriasis in difficult to treat areas such as the scalp and nails.

There were no serious adverse events. Two patients developed grade 2 neutropenia. Two patients showed elevations in liver enzymes that subsided when the drug was discontinued.

Both groups of investigators said their findings demonstrate that interleukin-17 is an appropriate target for psoriasis treatment. They also noted that the phase-II studies were too small and too brief to assess these agents’ effects on the risk of infection and cardiovascular events, and noted that further, longer-term studies of safety and efficacy are needed.

Even though there were few adverse effects in these two clinical trials and few patients withdrew from the studies, "a 12-week follow-up period is too short to assess the safety of treatments targeting interleukin-17," said Ari Waisman, Ph.D., in remarks taken from his editorial accompanying the reports on brodalumab and ixekizumab (N. Engl. J. Med. 2012;366:1251-2).

Despite the patients’ marked improvements with both brodalumab and ixekizumab, "future trials involving larger numbers of patients treated and followed for a much longer period of time will be needed," Dr. Waisman of the Institute for Molecular Medicine at Johannes-Gutenberg University of Mainz (Germany) said.

Dr. Papp’s study was funded by Amgen; Dr. Papp and his associates reported ties to numerous industry sources. Dr. Leonardi’s study was funded by Eli Lilly; Dr. Leonardi reported ties to Abbott, Amgen, Celgene, Centocor, Eli Lilly, Pfizer, Galderma, Incyte, Maruho, Schering-Plough, Sirtris, Stiefel, Novartis, Novo Nordisk, Vascular Biogenics, and Wyeth. Dr. Waisman reported ties to Teva, Phenex, and GlaxoSmithKline.

SAN DIEGO – An investigational first-in-class drug not only improved plaque psoriasis but reduced atherosclerotic inflammation in major vessels, a study has shown.

At 12 weeks there was a dose-related response in inflammation in the most-diseased vessels. Those in the placebo group had a 4% decrease in the target-to-baseline ratio (a validated PET/CT measure of changes in vessel inflammation), while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"As we look at our patients with psoriasis, where cardiovascular risk factors are a huge public health problem, this type of approach may have multiple benefits for them," said Dr. Alexa B. Kimball, who presented the results at the annual meeting of the American Academy of Dermatology.

The results come from a phase II trial of 184 patients with moderate to severe plaque psoriasis and a PET/CT substudy of 47 patients with cardiovascular risk factors. The patients in the double-blind, randomized, placebo-controlled study received either 20 or 80 mg of VB-201 or placebo once daily for 12 weeks.

VB-201, a phospholipid analogue, is being developed by VBL Therapeutics as an oral disease-modifying agent for chronic immunoinflammatory disease and atherosclerosis inflammation, and is the first in the lecinoxoid molecular class.

The compound’s novel mechanism of action for the control and attenuation of chronic immunoinflammatory diseases is thought to be through the highly selective modulation of components of the innate immune system. The drug is proposed to work by inhibiting cell-surface toll-like receptor signal cascade. "It’s mimicking some of the native molecules, but this turns out to be specific to antigen-presenting cells, endothelial cells, and monocytes," said Dr. Kimball. Thus, chemokine-mediated migration of monocytes to inflamed tissue is limited.

In the subanalysis, patients had to have a target-to-baseline ratio on PET/CT scan that was greater than 1.6 in order to be eligible.

PET/CT was used to evaluate inflammation in the vessels over time. The primary endpoint in this substudy included the mean of the maximum values of the target-to-baseline ratio in the most-diseased segment of vessel. The secondary endpoint involved looking at all of the inflammation in the vessels to determine a mean value for the vessels in a given patient; these mean values were then used to calculate an overall mean value of inflammation.

"One of the challenges in cardiovascular studies looking at atherosclerotic disease is that the endpoint that you’re most interested in is actually myocardial infarction, typically," said Dr. Kimball. "This form of PET/CT has been shown to be a pretty sensitive measure for inflammation in these vessels and is being used in investigational settings to be a surrogate marker for risk."

In addition, the technique correlates well with histopathologic inflammation and with cardiovascular risk factors. "It also seems to be predictive of future clinical vascular events," she said. High-fluorine-¹⁸fluorodeoxyglucose uptake appears to correlate with future vascular events.

"We did enhance the substudy with patients with additional cardiovascular risk factors to make sure that we had a population at risk where we actually could see inflammation to begin with," she said.

In the substudy, 13 patients were on placebo, 18 were on 20 mg VB-201, and 16 were taking 80 mg VB-201. These patients were a little older and had such risk factors as vascular disease dyslipidemia, diabetes, and obesity. Many were on statins.

At 12 weeks, there was a dose-related response in inflammation in the most-diseased vessel. Those in the placebo group had a 4% decrease in target-to-baseline ratio, while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"To put that into context with high-dose statin therapy, we would typically see these types of responses in the 7%-10% reduction range usually over 6 months rather than just 3 months," said Dr. Kimball of the dermatology department at Massachusetts General Hospital in Boston.

In the main study, the researchers looked at the effects of the drug on plaque psoriasis, compared with placebo. The primary endpoint was a Psoriasis Area and Severity Index (PASI) score of 75.

The 184 patients were randomized to receive 20 mg VB-201 (66), 80 mg VB-201 (59), or placebo (59). The study cohort was primarily composed of overweight men (BMI approximately 30 kg/m²) with an average age of 45 years. Overall, the group had a baseline PASI score close to 20.

Statistically significant improvements were achieved on the Physician Global Assessment and Patient Global Assessment. In terms of PASI 75, "there was a dose response as well," said Dr. Kimball. "This is not a drug that is achieving high levels of PASI 90 or PASI 100 ... but there is some benefit."

"This drug is moving people from substantial severity to reduced severity ... It may not be a drug that clears psoriasis to zero, but you can move patients out of the severe category," she said.

"VBL-201 is thought to be – at least in these initial studies – quite well tolerated. ... The study met its primary endpoint in the PET-CT substudy, demonstrating a statistically significant reduction in vascular inflammation," Dr. Kimball noted. "Importantly, these reductions occurred also in patients who were on statin therapy."

There were no treatment-related serious adverse events; the overall rates of adverse events were similar for both doses of VB-201 drug and placebo.

The study was funded by VBL Pharmaceuticals. Dr. Kimball is a consultant for VBL and several other pharmaceutical companies.

SAN DIEGO – An investigational first-in-class drug not only improved plaque psoriasis but reduced atherosclerotic inflammation in major vessels, a study has shown.

At 12 weeks there was a dose-related response in inflammation in the most-diseased vessels. Those in the placebo group had a 4% decrease in the target-to-baseline ratio (a validated PET/CT measure of changes in vessel inflammation), while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"As we look at our patients with psoriasis, where cardiovascular risk factors are a huge public health problem, this type of approach may have multiple benefits for them," said Dr. Alexa B. Kimball, who presented the results at the annual meeting of the American Academy of Dermatology.

The results come from a phase II trial of 184 patients with moderate to severe plaque psoriasis and a PET/CT substudy of 47 patients with cardiovascular risk factors. The patients in the double-blind, randomized, placebo-controlled study received either 20 or 80 mg of VB-201 or placebo once daily for 12 weeks.

VB-201, a phospholipid analogue, is being developed by VBL Therapeutics as an oral disease-modifying agent for chronic immunoinflammatory disease and atherosclerosis inflammation, and is the first in the lecinoxoid molecular class.

The compound’s novel mechanism of action for the control and attenuation of chronic immunoinflammatory diseases is thought to be through the highly selective modulation of components of the innate immune system. The drug is proposed to work by inhibiting cell-surface toll-like receptor signal cascade. "It’s mimicking some of the native molecules, but this turns out to be specific to antigen-presenting cells, endothelial cells, and monocytes," said Dr. Kimball. Thus, chemokine-mediated migration of monocytes to inflamed tissue is limited.

In the subanalysis, patients had to have a target-to-baseline ratio on PET/CT scan that was greater than 1.6 in order to be eligible.

PET/CT was used to evaluate inflammation in the vessels over time. The primary endpoint in this substudy included the mean of the maximum values of the target-to-baseline ratio in the most-diseased segment of vessel. The secondary endpoint involved looking at all of the inflammation in the vessels to determine a mean value for the vessels in a given patient; these mean values were then used to calculate an overall mean value of inflammation.

"One of the challenges in cardiovascular studies looking at atherosclerotic disease is that the endpoint that you’re most interested in is actually myocardial infarction, typically," said Dr. Kimball. "This form of PET/CT has been shown to be a pretty sensitive measure for inflammation in these vessels and is being used in investigational settings to be a surrogate marker for risk."

In addition, the technique correlates well with histopathologic inflammation and with cardiovascular risk factors. "It also seems to be predictive of future clinical vascular events," she said. High-fluorine-¹⁸fluorodeoxyglucose uptake appears to correlate with future vascular events.

"We did enhance the substudy with patients with additional cardiovascular risk factors to make sure that we had a population at risk where we actually could see inflammation to begin with," she said.

In the substudy, 13 patients were on placebo, 18 were on 20 mg VB-201, and 16 were taking 80 mg VB-201. These patients were a little older and had such risk factors as vascular disease dyslipidemia, diabetes, and obesity. Many were on statins.

At 12 weeks, there was a dose-related response in inflammation in the most-diseased vessel. Those in the placebo group had a 4% decrease in target-to-baseline ratio, while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"To put that into context with high-dose statin therapy, we would typically see these types of responses in the 7%-10% reduction range usually over 6 months rather than just 3 months," said Dr. Kimball of the dermatology department at Massachusetts General Hospital in Boston.

In the main study, the researchers looked at the effects of the drug on plaque psoriasis, compared with placebo. The primary endpoint was a Psoriasis Area and Severity Index (PASI) score of 75.

The 184 patients were randomized to receive 20 mg VB-201 (66), 80 mg VB-201 (59), or placebo (59). The study cohort was primarily composed of overweight men (BMI approximately 30 kg/m²) with an average age of 45 years. Overall, the group had a baseline PASI score close to 20.

Statistically significant improvements were achieved on the Physician Global Assessment and Patient Global Assessment. In terms of PASI 75, "there was a dose response as well," said Dr. Kimball. "This is not a drug that is achieving high levels of PASI 90 or PASI 100 ... but there is some benefit."

"This drug is moving people from substantial severity to reduced severity ... It may not be a drug that clears psoriasis to zero, but you can move patients out of the severe category," she said.

"VBL-201 is thought to be – at least in these initial studies – quite well tolerated. ... The study met its primary endpoint in the PET-CT substudy, demonstrating a statistically significant reduction in vascular inflammation," Dr. Kimball noted. "Importantly, these reductions occurred also in patients who were on statin therapy."

There were no treatment-related serious adverse events; the overall rates of adverse events were similar for both doses of VB-201 drug and placebo.

The study was funded by VBL Pharmaceuticals. Dr. Kimball is a consultant for VBL and several other pharmaceutical companies.

SAN DIEGO – An investigational first-in-class drug not only improved plaque psoriasis but reduced atherosclerotic inflammation in major vessels, a study has shown.

At 12 weeks there was a dose-related response in inflammation in the most-diseased vessels. Those in the placebo group had a 4% decrease in the target-to-baseline ratio (a validated PET/CT measure of changes in vessel inflammation), while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"As we look at our patients with psoriasis, where cardiovascular risk factors are a huge public health problem, this type of approach may have multiple benefits for them," said Dr. Alexa B. Kimball, who presented the results at the annual meeting of the American Academy of Dermatology.

The results come from a phase II trial of 184 patients with moderate to severe plaque psoriasis and a PET/CT substudy of 47 patients with cardiovascular risk factors. The patients in the double-blind, randomized, placebo-controlled study received either 20 or 80 mg of VB-201 or placebo once daily for 12 weeks.

VB-201, a phospholipid analogue, is being developed by VBL Therapeutics as an oral disease-modifying agent for chronic immunoinflammatory disease and atherosclerosis inflammation, and is the first in the lecinoxoid molecular class.

The compound’s novel mechanism of action for the control and attenuation of chronic immunoinflammatory diseases is thought to be through the highly selective modulation of components of the innate immune system. The drug is proposed to work by inhibiting cell-surface toll-like receptor signal cascade. "It’s mimicking some of the native molecules, but this turns out to be specific to antigen-presenting cells, endothelial cells, and monocytes," said Dr. Kimball. Thus, chemokine-mediated migration of monocytes to inflamed tissue is limited.

In the subanalysis, patients had to have a target-to-baseline ratio on PET/CT scan that was greater than 1.6 in order to be eligible.

PET/CT was used to evaluate inflammation in the vessels over time. The primary endpoint in this substudy included the mean of the maximum values of the target-to-baseline ratio in the most-diseased segment of vessel. The secondary endpoint involved looking at all of the inflammation in the vessels to determine a mean value for the vessels in a given patient; these mean values were then used to calculate an overall mean value of inflammation.

"One of the challenges in cardiovascular studies looking at atherosclerotic disease is that the endpoint that you’re most interested in is actually myocardial infarction, typically," said Dr. Kimball. "This form of PET/CT has been shown to be a pretty sensitive measure for inflammation in these vessels and is being used in investigational settings to be a surrogate marker for risk."

In addition, the technique correlates well with histopathologic inflammation and with cardiovascular risk factors. "It also seems to be predictive of future clinical vascular events," she said. High-fluorine-¹⁸fluorodeoxyglucose uptake appears to correlate with future vascular events.

"We did enhance the substudy with patients with additional cardiovascular risk factors to make sure that we had a population at risk where we actually could see inflammation to begin with," she said.

In the substudy, 13 patients were on placebo, 18 were on 20 mg VB-201, and 16 were taking 80 mg VB-201. These patients were a little older and had such risk factors as vascular disease dyslipidemia, diabetes, and obesity. Many were on statins.

At 12 weeks, there was a dose-related response in inflammation in the most-diseased vessel. Those in the placebo group had a 4% decrease in target-to-baseline ratio, while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"To put that into context with high-dose statin therapy, we would typically see these types of responses in the 7%-10% reduction range usually over 6 months rather than just 3 months," said Dr. Kimball of the dermatology department at Massachusetts General Hospital in Boston.

In the main study, the researchers looked at the effects of the drug on plaque psoriasis, compared with placebo. The primary endpoint was a Psoriasis Area and Severity Index (PASI) score of 75.

The 184 patients were randomized to receive 20 mg VB-201 (66), 80 mg VB-201 (59), or placebo (59). The study cohort was primarily composed of overweight men (BMI approximately 30 kg/m²) with an average age of 45 years. Overall, the group had a baseline PASI score close to 20.

Statistically significant improvements were achieved on the Physician Global Assessment and Patient Global Assessment. In terms of PASI 75, "there was a dose response as well," said Dr. Kimball. "This is not a drug that is achieving high levels of PASI 90 or PASI 100 ... but there is some benefit."

"This drug is moving people from substantial severity to reduced severity ... It may not be a drug that clears psoriasis to zero, but you can move patients out of the severe category," she said.

"VBL-201 is thought to be – at least in these initial studies – quite well tolerated. ... The study met its primary endpoint in the PET-CT substudy, demonstrating a statistically significant reduction in vascular inflammation," Dr. Kimball noted. "Importantly, these reductions occurred also in patients who were on statin therapy."

There were no treatment-related serious adverse events; the overall rates of adverse events were similar for both doses of VB-201 drug and placebo.

The study was funded by VBL Pharmaceuticals. Dr. Kimball is a consultant for VBL and several other pharmaceutical companies.

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

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

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

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

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

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

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

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

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

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

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

She reported having no financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

She reported having no financial conflicts.

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

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

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

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

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

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

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

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

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

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

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

She reported having no financial conflicts.