Psoriasis

KYOTO, JAPAN — The annual incidence of both bullous pemphigoid and pemphigus vulgaris has climbed steadily over the past decade in the United Kingdom for reasons unknown, according to a study of more than 1,000 patients.

The mortality associated with these autoimmune diseases may have been underestimated in the past, based upon the results of Dr. Sinéad Langan's large, population-based study presented at an international investigative dermatology meeting.

"People with bullous pemphigoid are twice as likely to die and those with pemphigus vulgaris are three times as likely to die as [are] matched controls," said Dr. Langan of the University of Nottingham (England).

Her study of The Health Improvement Network (THIN)—a large, population-based database of computerized primary care medical records—identified 868 patients diagnosed with bullous pemphigoid (BP) and 139 diagnosed with pemphigus vulgaris (PV) during 1996-2006. Each patient was matched by age and gender with four controls from the same general practice.

She undertook the study because, despite the substantial morbidity and mortality associated with these autoimmune diseases, little is known about their epidemiology. For example, there are only two published studies addressing PV mortality; one, from the Middle East, reported a 1-year mortality of 5%, while a 1975 U.S. study found a 50% 1-year mortality, she said. The reported BP mortality has cut a similarly wide swath.

The incidence of BP in the new U.K. study climbed with advancing age, peaking in a group aged 80-84 years. The median age at presentation was 80 years, and 62% of affected patients were women.

PV incidence showed a bimodal distribution, with a peak at ages 45-49 years and a second, larger one at 80-84 years. Median age at presentation was 71 years, and two-thirds of patients were women.

The incidence of BP was 4.3 cases/100,000 person-years; for PV it was 0.7/100,000 person-years. The incidence of BP showed a "dramatic" average yearly increase of 17% during the study period, while PV incidence increased by 11% each year, according to Dr. Langan. The 1-year mortality rate among patients with BP was 19%, resulting in an estimated 70 excess deaths/1,000 person-years. After adjustment for age and gender as potential confounders, BP patients had a 2.3-fold greater risk of mortality than did controls. The adjusted mortality risk in PV patients was 3.4-fold greater than in controls; PV resulted in 62 excess deaths/100,000 person-years.

Dr. Joel M. Gelfand commented that he doesn't believe the rising annual incidence rates of BP and PV observed in the U.K. study are real, and suspects that more sophisticated statistical analyses would show as much.

"If you look at these kinds of data sets across almost all diseases, the incidence seems to increase over time. It's probably an issue of chronic diseases being picked up over time," according to Dr. Gelfand, who has led several landmark studies carefully documenting increased cardiovascular and cerebrovascular risks in psoriasis patients using the U.K. General Practice Research Database. He is medical director of the clinical studies unit in the department of dermatology at the University of Pennsylvania, Philadelphia.

Dr. John R. Stanley, professor and chair of dermatology at the University of Pennsylvania, said Dr. Langan's study left him uncertain about how to apply the findings in clinical practice. "We don't know [from the U.K. study] whether to treat more aggressively or less," Dr. Stanley observed at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Langan agreed these data are not illuminating on that score. However, the database also contains information on medications, and she is planning a study she hopes will help guide treatment decisions.

'People with bullous pemphigoid are twice as likely to die and those with pemphigus vulgaris are three times as likely.' DR. LANGAN

KYOTO, JAPAN — The annual incidence of both bullous pemphigoid and pemphigus vulgaris has climbed steadily over the past decade in the United Kingdom for reasons unknown, according to a study of more than 1,000 patients.

The mortality associated with these autoimmune diseases may have been underestimated in the past, based upon the results of Dr. Sinéad Langan's large, population-based study presented at an international investigative dermatology meeting.

"People with bullous pemphigoid are twice as likely to die and those with pemphigus vulgaris are three times as likely to die as [are] matched controls," said Dr. Langan of the University of Nottingham (England).

Her study of The Health Improvement Network (THIN)—a large, population-based database of computerized primary care medical records—identified 868 patients diagnosed with bullous pemphigoid (BP) and 139 diagnosed with pemphigus vulgaris (PV) during 1996-2006. Each patient was matched by age and gender with four controls from the same general practice.

She undertook the study because, despite the substantial morbidity and mortality associated with these autoimmune diseases, little is known about their epidemiology. For example, there are only two published studies addressing PV mortality; one, from the Middle East, reported a 1-year mortality of 5%, while a 1975 U.S. study found a 50% 1-year mortality, she said. The reported BP mortality has cut a similarly wide swath.

The incidence of BP in the new U.K. study climbed with advancing age, peaking in a group aged 80-84 years. The median age at presentation was 80 years, and 62% of affected patients were women.

PV incidence showed a bimodal distribution, with a peak at ages 45-49 years and a second, larger one at 80-84 years. Median age at presentation was 71 years, and two-thirds of patients were women.

The incidence of BP was 4.3 cases/100,000 person-years; for PV it was 0.7/100,000 person-years. The incidence of BP showed a "dramatic" average yearly increase of 17% during the study period, while PV incidence increased by 11% each year, according to Dr. Langan. The 1-year mortality rate among patients with BP was 19%, resulting in an estimated 70 excess deaths/1,000 person-years. After adjustment for age and gender as potential confounders, BP patients had a 2.3-fold greater risk of mortality than did controls. The adjusted mortality risk in PV patients was 3.4-fold greater than in controls; PV resulted in 62 excess deaths/100,000 person-years.

Dr. Joel M. Gelfand commented that he doesn't believe the rising annual incidence rates of BP and PV observed in the U.K. study are real, and suspects that more sophisticated statistical analyses would show as much.

"If you look at these kinds of data sets across almost all diseases, the incidence seems to increase over time. It's probably an issue of chronic diseases being picked up over time," according to Dr. Gelfand, who has led several landmark studies carefully documenting increased cardiovascular and cerebrovascular risks in psoriasis patients using the U.K. General Practice Research Database. He is medical director of the clinical studies unit in the department of dermatology at the University of Pennsylvania, Philadelphia.

Dr. John R. Stanley, professor and chair of dermatology at the University of Pennsylvania, said Dr. Langan's study left him uncertain about how to apply the findings in clinical practice. "We don't know [from the U.K. study] whether to treat more aggressively or less," Dr. Stanley observed at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Langan agreed these data are not illuminating on that score. However, the database also contains information on medications, and she is planning a study she hopes will help guide treatment decisions.

'People with bullous pemphigoid are twice as likely to die and those with pemphigus vulgaris are three times as likely.' DR. LANGAN

KYOTO, JAPAN — The annual incidence of both bullous pemphigoid and pemphigus vulgaris has climbed steadily over the past decade in the United Kingdom for reasons unknown, according to a study of more than 1,000 patients.

The mortality associated with these autoimmune diseases may have been underestimated in the past, based upon the results of Dr. Sinéad Langan's large, population-based study presented at an international investigative dermatology meeting.

"People with bullous pemphigoid are twice as likely to die and those with pemphigus vulgaris are three times as likely to die as [are] matched controls," said Dr. Langan of the University of Nottingham (England).

Her study of The Health Improvement Network (THIN)—a large, population-based database of computerized primary care medical records—identified 868 patients diagnosed with bullous pemphigoid (BP) and 139 diagnosed with pemphigus vulgaris (PV) during 1996-2006. Each patient was matched by age and gender with four controls from the same general practice.

She undertook the study because, despite the substantial morbidity and mortality associated with these autoimmune diseases, little is known about their epidemiology. For example, there are only two published studies addressing PV mortality; one, from the Middle East, reported a 1-year mortality of 5%, while a 1975 U.S. study found a 50% 1-year mortality, she said. The reported BP mortality has cut a similarly wide swath.

The incidence of BP in the new U.K. study climbed with advancing age, peaking in a group aged 80-84 years. The median age at presentation was 80 years, and 62% of affected patients were women.

PV incidence showed a bimodal distribution, with a peak at ages 45-49 years and a second, larger one at 80-84 years. Median age at presentation was 71 years, and two-thirds of patients were women.

The incidence of BP was 4.3 cases/100,000 person-years; for PV it was 0.7/100,000 person-years. The incidence of BP showed a "dramatic" average yearly increase of 17% during the study period, while PV incidence increased by 11% each year, according to Dr. Langan. The 1-year mortality rate among patients with BP was 19%, resulting in an estimated 70 excess deaths/1,000 person-years. After adjustment for age and gender as potential confounders, BP patients had a 2.3-fold greater risk of mortality than did controls. The adjusted mortality risk in PV patients was 3.4-fold greater than in controls; PV resulted in 62 excess deaths/100,000 person-years.

Dr. Joel M. Gelfand commented that he doesn't believe the rising annual incidence rates of BP and PV observed in the U.K. study are real, and suspects that more sophisticated statistical analyses would show as much.

"If you look at these kinds of data sets across almost all diseases, the incidence seems to increase over time. It's probably an issue of chronic diseases being picked up over time," according to Dr. Gelfand, who has led several landmark studies carefully documenting increased cardiovascular and cerebrovascular risks in psoriasis patients using the U.K. General Practice Research Database. He is medical director of the clinical studies unit in the department of dermatology at the University of Pennsylvania, Philadelphia.

Dr. John R. Stanley, professor and chair of dermatology at the University of Pennsylvania, said Dr. Langan's study left him uncertain about how to apply the findings in clinical practice. "We don't know [from the U.K. study] whether to treat more aggressively or less," Dr. Stanley observed at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Langan agreed these data are not illuminating on that score. However, the database also contains information on medications, and she is planning a study she hopes will help guide treatment decisions.

'People with bullous pemphigoid are twice as likely to die and those with pemphigus vulgaris are three times as likely.' DR. LANGAN

KYOTO, JAPAN — More than 7% of individuals without any form of autoimmune disease possess elevated serum bullous pemphigoid 180 and/or BP230 autoantibodies on the commercially available enzyme-linked immunosorbent assay, according to testing of stored serum from 370 people.

These autoantibodies have been considered diagnostic for bullous pemphigoid, the most common cutaneous autoimmune bullous disorder, but that is clearly not the case, Dr. Nneka I. Comfrere of the Mayo Clinic in Rochester, Minn., reported at an international investigative dermatology meeting.

"I think there's not one test we can clearly rely on to make the diagnosis. What we've concluded at the Mayo Clinic is disease confirmation requires a correlation of multiple measures, including the clinical pattern, the presentation of disease, routine histopathology, and both direct and indirect immunofluorescence studies, as well as the ELISA [enzyme-linked immunosorbent assay], in order to ensure the highest diagnostic accuracy. Clearly, one cannot rely solely on the ELISA," she said.

Dr. Comfrere and her associates examined the prevalence of circulating BP180 and BP230 autoantibodies across the age spectrum of individuals who did not have bullous pemphigoid or any other autoimmune disease. They tested stored serum from patients aged 20 years to more than 90 years.

A positive test for one or both autoantibodies, defined by the manufacturer as a level of nine units or more, was detected in 7.4% of subjects. The prevalence did not vary by decade of life or by gender. Moreover, the geometric mean titer also remained similar across the decades, she said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Audience members raised the possibility that the presence of circulating autoantibodies in asymptomatic individuals might precede clinical manifestations of the disease, but the finding that prevalence of the autoantibodies was similar across the decades rather than peaking in the elderly argues against this, Dr. Comfrere noted.

The role of these autoantibodies in initiating and perpetuating the disease process remains unclear, she added. It's possible that the development of clinical bullous pemphigoid requires exogenous factors in susceptible individuals.

KYOTO, JAPAN — More than 7% of individuals without any form of autoimmune disease possess elevated serum bullous pemphigoid 180 and/or BP230 autoantibodies on the commercially available enzyme-linked immunosorbent assay, according to testing of stored serum from 370 people.

These autoantibodies have been considered diagnostic for bullous pemphigoid, the most common cutaneous autoimmune bullous disorder, but that is clearly not the case, Dr. Nneka I. Comfrere of the Mayo Clinic in Rochester, Minn., reported at an international investigative dermatology meeting.

"I think there's not one test we can clearly rely on to make the diagnosis. What we've concluded at the Mayo Clinic is disease confirmation requires a correlation of multiple measures, including the clinical pattern, the presentation of disease, routine histopathology, and both direct and indirect immunofluorescence studies, as well as the ELISA [enzyme-linked immunosorbent assay], in order to ensure the highest diagnostic accuracy. Clearly, one cannot rely solely on the ELISA," she said.

Dr. Comfrere and her associates examined the prevalence of circulating BP180 and BP230 autoantibodies across the age spectrum of individuals who did not have bullous pemphigoid or any other autoimmune disease. They tested stored serum from patients aged 20 years to more than 90 years.

A positive test for one or both autoantibodies, defined by the manufacturer as a level of nine units or more, was detected in 7.4% of subjects. The prevalence did not vary by decade of life or by gender. Moreover, the geometric mean titer also remained similar across the decades, she said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Audience members raised the possibility that the presence of circulating autoantibodies in asymptomatic individuals might precede clinical manifestations of the disease, but the finding that prevalence of the autoantibodies was similar across the decades rather than peaking in the elderly argues against this, Dr. Comfrere noted.

The role of these autoantibodies in initiating and perpetuating the disease process remains unclear, she added. It's possible that the development of clinical bullous pemphigoid requires exogenous factors in susceptible individuals.

KYOTO, JAPAN — More than 7% of individuals without any form of autoimmune disease possess elevated serum bullous pemphigoid 180 and/or BP230 autoantibodies on the commercially available enzyme-linked immunosorbent assay, according to testing of stored serum from 370 people.

These autoantibodies have been considered diagnostic for bullous pemphigoid, the most common cutaneous autoimmune bullous disorder, but that is clearly not the case, Dr. Nneka I. Comfrere of the Mayo Clinic in Rochester, Minn., reported at an international investigative dermatology meeting.

"I think there's not one test we can clearly rely on to make the diagnosis. What we've concluded at the Mayo Clinic is disease confirmation requires a correlation of multiple measures, including the clinical pattern, the presentation of disease, routine histopathology, and both direct and indirect immunofluorescence studies, as well as the ELISA [enzyme-linked immunosorbent assay], in order to ensure the highest diagnostic accuracy. Clearly, one cannot rely solely on the ELISA," she said.

Dr. Comfrere and her associates examined the prevalence of circulating BP180 and BP230 autoantibodies across the age spectrum of individuals who did not have bullous pemphigoid or any other autoimmune disease. They tested stored serum from patients aged 20 years to more than 90 years.

A positive test for one or both autoantibodies, defined by the manufacturer as a level of nine units or more, was detected in 7.4% of subjects. The prevalence did not vary by decade of life or by gender. Moreover, the geometric mean titer also remained similar across the decades, she said at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Audience members raised the possibility that the presence of circulating autoantibodies in asymptomatic individuals might precede clinical manifestations of the disease, but the finding that prevalence of the autoantibodies was similar across the decades rather than peaking in the elderly argues against this, Dr. Comfrere noted.

The role of these autoantibodies in initiating and perpetuating the disease process remains unclear, she added. It's possible that the development of clinical bullous pemphigoid requires exogenous factors in susceptible individuals.

Low-dose methotrexate combined with topical betamethasone dipropionate was a safe and effective treatment for bullous pemphigoid in a retrospective study conducted by Dr. Petra Kjellman and colleagues.

For the past 50 years, glucocorticoids have been the mainstay of treatment for bullous pemphigoid (BP), but the high doses of these drugs that are typically needed to control inflammation are poorly tolerated, particularly among the elderly, who are most commonly affected, according to the researchers.

To minimize the adverse effects of glucocorticoids, which include sepsis, pneumonia, gastrointestinal tract bleeding, diabetes, and osteoporosis, other immunosuppressants also have been tried as steroid-sparing agents in BP, but few controlled trials have been done, they noted.

For the past decade, Dr. Kjellman and colleagues from the department of dermatology and venereology, Karolinska University Hospital, Stockholm, have preferentially used methotrexate for BP patients, with prednisone if needed or if methotrexate could not be given or tolerated.

The usual regimen involved an initial dosage of 5 mg/week of methotrexate, with topical betamethasone dipropionate applied twice daily until the disease was controlled. If necessary, methotrexate dosage was increased by 2.5 mg/week.

If symptoms persisted despite methotrexate treatment, prednisone was added in doses of 10-20 mg/day, and if methotrexate could not be given because of anemia, liver disease, or renal failure, prednisone was given alone.

Between 1999 and 2003, 138 patients whose mean age was 81 years were diagnosed with BP. Of these, 57% were women, 51% had mild disease, 38% had moderate disease, and 11% had severe disease.

Methotrexate treatment was initiated in 98 (71%), with a median weekly dosage of 5 mg. Among these patients, 61 continued on methotrexate monotherapy (group 1) and had a mean cumulative dose of 280 mg.

Among patients who received methotrexate, 37 also were treated with prednisone (group 2). The median weekly dosage of methotrexate in this group was 6 mg, and the median cumulative dose was 440 mg.

Forty patients did not receive methotrexate, with 15 receiving high-dose prednisone alone at a median daily dosage of 12 mg and with a median cumulative dose of 4,000 mg (group 3). The other 25 patients who did not receive methotrexate (group 4) had mild disease and were managed with topical betamethasone gel alone.

Median follow-up was 26 months. At 24 months, the remission rates were 43% in group 1, 35% in group 2, 0% in group 3, and 83% in group 4 (Arch. Dermatol. 2008;144:612-16).

Mortality in BP is considerable, with previous reports finding 1-year mortality ranging from 10% to 41%, according to the researchers. In this series, 2-year survival was 65%, 67%, 47%, and 52% in the four groups, respectively, and there was a tendency toward better survival for the methotrexate-treated patients, with median survival times of 38 and 24 months in groups 1 and 2, respectively.

Only one patient in this series developed anemia, and although elevated liver enzymes were seen on occasion during the first weeks of therapy, normalization usually followed within 4-6 weeks. They did not perform pretreatment liver biopsies.

They researchers noted that they are also developing a BP quality register and biobank to enable further follow-up of these patients, and they plan a prospective study to provide further information. They had no conflicts of interest to disclose.

Low-dose methotrexate combined with topical betamethasone dipropionate was a safe and effective treatment for bullous pemphigoid in a retrospective study conducted by Dr. Petra Kjellman and colleagues.

For the past 50 years, glucocorticoids have been the mainstay of treatment for bullous pemphigoid (BP), but the high doses of these drugs that are typically needed to control inflammation are poorly tolerated, particularly among the elderly, who are most commonly affected, according to the researchers.

To minimize the adverse effects of glucocorticoids, which include sepsis, pneumonia, gastrointestinal tract bleeding, diabetes, and osteoporosis, other immunosuppressants also have been tried as steroid-sparing agents in BP, but few controlled trials have been done, they noted.

For the past decade, Dr. Kjellman and colleagues from the department of dermatology and venereology, Karolinska University Hospital, Stockholm, have preferentially used methotrexate for BP patients, with prednisone if needed or if methotrexate could not be given or tolerated.

The usual regimen involved an initial dosage of 5 mg/week of methotrexate, with topical betamethasone dipropionate applied twice daily until the disease was controlled. If necessary, methotrexate dosage was increased by 2.5 mg/week.

If symptoms persisted despite methotrexate treatment, prednisone was added in doses of 10-20 mg/day, and if methotrexate could not be given because of anemia, liver disease, or renal failure, prednisone was given alone.

Between 1999 and 2003, 138 patients whose mean age was 81 years were diagnosed with BP. Of these, 57% were women, 51% had mild disease, 38% had moderate disease, and 11% had severe disease.

Methotrexate treatment was initiated in 98 (71%), with a median weekly dosage of 5 mg. Among these patients, 61 continued on methotrexate monotherapy (group 1) and had a mean cumulative dose of 280 mg.

Among patients who received methotrexate, 37 also were treated with prednisone (group 2). The median weekly dosage of methotrexate in this group was 6 mg, and the median cumulative dose was 440 mg.

Forty patients did not receive methotrexate, with 15 receiving high-dose prednisone alone at a median daily dosage of 12 mg and with a median cumulative dose of 4,000 mg (group 3). The other 25 patients who did not receive methotrexate (group 4) had mild disease and were managed with topical betamethasone gel alone.

Median follow-up was 26 months. At 24 months, the remission rates were 43% in group 1, 35% in group 2, 0% in group 3, and 83% in group 4 (Arch. Dermatol. 2008;144:612-16).

Mortality in BP is considerable, with previous reports finding 1-year mortality ranging from 10% to 41%, according to the researchers. In this series, 2-year survival was 65%, 67%, 47%, and 52% in the four groups, respectively, and there was a tendency toward better survival for the methotrexate-treated patients, with median survival times of 38 and 24 months in groups 1 and 2, respectively.

Only one patient in this series developed anemia, and although elevated liver enzymes were seen on occasion during the first weeks of therapy, normalization usually followed within 4-6 weeks. They did not perform pretreatment liver biopsies.

They researchers noted that they are also developing a BP quality register and biobank to enable further follow-up of these patients, and they plan a prospective study to provide further information. They had no conflicts of interest to disclose.

Low-dose methotrexate combined with topical betamethasone dipropionate was a safe and effective treatment for bullous pemphigoid in a retrospective study conducted by Dr. Petra Kjellman and colleagues.

For the past 50 years, glucocorticoids have been the mainstay of treatment for bullous pemphigoid (BP), but the high doses of these drugs that are typically needed to control inflammation are poorly tolerated, particularly among the elderly, who are most commonly affected, according to the researchers.

To minimize the adverse effects of glucocorticoids, which include sepsis, pneumonia, gastrointestinal tract bleeding, diabetes, and osteoporosis, other immunosuppressants also have been tried as steroid-sparing agents in BP, but few controlled trials have been done, they noted.

For the past decade, Dr. Kjellman and colleagues from the department of dermatology and venereology, Karolinska University Hospital, Stockholm, have preferentially used methotrexate for BP patients, with prednisone if needed or if methotrexate could not be given or tolerated.

The usual regimen involved an initial dosage of 5 mg/week of methotrexate, with topical betamethasone dipropionate applied twice daily until the disease was controlled. If necessary, methotrexate dosage was increased by 2.5 mg/week.

If symptoms persisted despite methotrexate treatment, prednisone was added in doses of 10-20 mg/day, and if methotrexate could not be given because of anemia, liver disease, or renal failure, prednisone was given alone.

Between 1999 and 2003, 138 patients whose mean age was 81 years were diagnosed with BP. Of these, 57% were women, 51% had mild disease, 38% had moderate disease, and 11% had severe disease.

Methotrexate treatment was initiated in 98 (71%), with a median weekly dosage of 5 mg. Among these patients, 61 continued on methotrexate monotherapy (group 1) and had a mean cumulative dose of 280 mg.

Among patients who received methotrexate, 37 also were treated with prednisone (group 2). The median weekly dosage of methotrexate in this group was 6 mg, and the median cumulative dose was 440 mg.

Forty patients did not receive methotrexate, with 15 receiving high-dose prednisone alone at a median daily dosage of 12 mg and with a median cumulative dose of 4,000 mg (group 3). The other 25 patients who did not receive methotrexate (group 4) had mild disease and were managed with topical betamethasone gel alone.

Median follow-up was 26 months. At 24 months, the remission rates were 43% in group 1, 35% in group 2, 0% in group 3, and 83% in group 4 (Arch. Dermatol. 2008;144:612-16).

Mortality in BP is considerable, with previous reports finding 1-year mortality ranging from 10% to 41%, according to the researchers. In this series, 2-year survival was 65%, 67%, 47%, and 52% in the four groups, respectively, and there was a tendency toward better survival for the methotrexate-treated patients, with median survival times of 38 and 24 months in groups 1 and 2, respectively.

Only one patient in this series developed anemia, and although elevated liver enzymes were seen on occasion during the first weeks of therapy, normalization usually followed within 4-6 weeks. They did not perform pretreatment liver biopsies.

They researchers noted that they are also developing a BP quality register and biobank to enable further follow-up of these patients, and they plan a prospective study to provide further information. They had no conflicts of interest to disclose.

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus, and physicians need to be aware of this, as well as other types of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female-to-male predominance, and the clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis.

It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to "classic" drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, according to Dr. Andrew G. Franks Jr.

"The likelihood of developing a lupuslike syndrome is elevated 8.5-fold with minocycline, so many clinicians are now moving away from using minocycline for acne and rosacea and switching to doxycycline, which really doesn't have this effect. I haven't used minocycline for 5 years," said Dr. Franks of the department of dermatology at New York University Medical Center, New York.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Younger physicians in particular might not be familiar with hydralazine's link to drug-induced lupus, Dr. Franks said.

Hydralazine is one of the five causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated, he said.

Classic drug-induced lupus is characterized by flulike symptoms and significant musculoskeletal involvement, with most patients being ANA and antihistone antibody positive. "In my opinion, patients starting hydralazine—or any drug in the big five, for that matter—should have a baseline test for ANA, although that is somewhat controversial," Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

Clinically, SCLE can be very difficult to sort out, according to Dr. Franks, with targetoid lesions mixed with papulosquamous or annular lesions. The presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin, he said.

An audience member asked what happens when the offending drug is withdrawn. Dr. Franks explained that the situation is different than an allergic reaction. "It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit," he said at a rheumatology meeting sponsored by New York University.

No single unifying mechanism has been identified that can explain the variety of drugs associated with drug-induced lupus or the varied clinical and laboratory manifestations. Hypotheses include the possibility that the drugs can act as haptens or antigens that drive an immune response, or as immune system modulators that permit the development of self-directed responses (Semin. Arthritis Rheum. 2007 Dec. 31 [doi:10.1016/j.semarthrit.2007.10.001]).

Dr. Franks reported having no financial relationships to disclose. n

The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline. DR. FRANKS

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus, and physicians need to be aware of this, as well as other types of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female-to-male predominance, and the clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis.

It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to "classic" drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, according to Dr. Andrew G. Franks Jr.

"The likelihood of developing a lupuslike syndrome is elevated 8.5-fold with minocycline, so many clinicians are now moving away from using minocycline for acne and rosacea and switching to doxycycline, which really doesn't have this effect. I haven't used minocycline for 5 years," said Dr. Franks of the department of dermatology at New York University Medical Center, New York.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Younger physicians in particular might not be familiar with hydralazine's link to drug-induced lupus, Dr. Franks said.

Hydralazine is one of the five causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated, he said.

Classic drug-induced lupus is characterized by flulike symptoms and significant musculoskeletal involvement, with most patients being ANA and antihistone antibody positive. "In my opinion, patients starting hydralazine—or any drug in the big five, for that matter—should have a baseline test for ANA, although that is somewhat controversial," Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

Clinically, SCLE can be very difficult to sort out, according to Dr. Franks, with targetoid lesions mixed with papulosquamous or annular lesions. The presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin, he said.

An audience member asked what happens when the offending drug is withdrawn. Dr. Franks explained that the situation is different than an allergic reaction. "It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit," he said at a rheumatology meeting sponsored by New York University.

No single unifying mechanism has been identified that can explain the variety of drugs associated with drug-induced lupus or the varied clinical and laboratory manifestations. Hypotheses include the possibility that the drugs can act as haptens or antigens that drive an immune response, or as immune system modulators that permit the development of self-directed responses (Semin. Arthritis Rheum. 2007 Dec. 31 [doi:10.1016/j.semarthrit.2007.10.001]).

Dr. Franks reported having no financial relationships to disclose. n

The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline. DR. FRANKS

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus, and physicians need to be aware of this, as well as other types of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female-to-male predominance, and the clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis.

It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to "classic" drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, according to Dr. Andrew G. Franks Jr.

"The likelihood of developing a lupuslike syndrome is elevated 8.5-fold with minocycline, so many clinicians are now moving away from using minocycline for acne and rosacea and switching to doxycycline, which really doesn't have this effect. I haven't used minocycline for 5 years," said Dr. Franks of the department of dermatology at New York University Medical Center, New York.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Younger physicians in particular might not be familiar with hydralazine's link to drug-induced lupus, Dr. Franks said.

Hydralazine is one of the five causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated, he said.

Classic drug-induced lupus is characterized by flulike symptoms and significant musculoskeletal involvement, with most patients being ANA and antihistone antibody positive. "In my opinion, patients starting hydralazine—or any drug in the big five, for that matter—should have a baseline test for ANA, although that is somewhat controversial," Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

Clinically, SCLE can be very difficult to sort out, according to Dr. Franks, with targetoid lesions mixed with papulosquamous or annular lesions. The presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin, he said.

An audience member asked what happens when the offending drug is withdrawn. Dr. Franks explained that the situation is different than an allergic reaction. "It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit," he said at a rheumatology meeting sponsored by New York University.

No single unifying mechanism has been identified that can explain the variety of drugs associated with drug-induced lupus or the varied clinical and laboratory manifestations. Hypotheses include the possibility that the drugs can act as haptens or antigens that drive an immune response, or as immune system modulators that permit the development of self-directed responses (Semin. Arthritis Rheum. 2007 Dec. 31 [doi:10.1016/j.semarthrit.2007.10.001]).

Dr. Franks reported having no financial relationships to disclose. n

The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline. DR. FRANKS

Manfred Kunz, MD

In recent years, DNA microarray technology has been used for the analysis of gene expression patterns in a variety of skin diseases, including malignant melanoma, psoriasis, lupus erythematosus, and systemic sclerosis. Many of the studies described herein confirmed earlier results on individual genes or functional groups of genes. However, a plethora of new candidate genes, gene patterns, and regulatory pathways have been identified. Major progresses were reached by the identification of a prognostic gene pattern in malignant melanoma, an immune signaling cluster in psoriasis, and a so-called interferon
signature in systemic lupus erythematosus. In future, interference with genes or regulatory pathways with the use of different RNA interference technologies or targeted therapy may not only underscore the functional significance of microarray data but also may open interesting therapeutic perspectives. Large-scale gene expression analyses may also help to design more individualized treatment approaches of cutaneous diseases.

*For a PDF of the full article, click on the link to the left of this introduction.

Manfred Kunz, MD

In recent years, DNA microarray technology has been used for the analysis of gene expression patterns in a variety of skin diseases, including malignant melanoma, psoriasis, lupus erythematosus, and systemic sclerosis. Many of the studies described herein confirmed earlier results on individual genes or functional groups of genes. However, a plethora of new candidate genes, gene patterns, and regulatory pathways have been identified. Major progresses were reached by the identification of a prognostic gene pattern in malignant melanoma, an immune signaling cluster in psoriasis, and a so-called interferon
signature in systemic lupus erythematosus. In future, interference with genes or regulatory pathways with the use of different RNA interference technologies or targeted therapy may not only underscore the functional significance of microarray data but also may open interesting therapeutic perspectives. Large-scale gene expression analyses may also help to design more individualized treatment approaches of cutaneous diseases.

*For a PDF of the full article, click on the link to the left of this introduction.

Manfred Kunz, MD

In recent years, DNA microarray technology has been used for the analysis of gene expression patterns in a variety of skin diseases, including malignant melanoma, psoriasis, lupus erythematosus, and systemic sclerosis. Many of the studies described herein confirmed earlier results on individual genes or functional groups of genes. However, a plethora of new candidate genes, gene patterns, and regulatory pathways have been identified. Major progresses were reached by the identification of a prognostic gene pattern in malignant melanoma, an immune signaling cluster in psoriasis, and a so-called interferon
signature in systemic lupus erythematosus. In future, interference with genes or regulatory pathways with the use of different RNA interference technologies or targeted therapy may not only underscore the functional significance of microarray data but also may open interesting therapeutic perspectives. Large-scale gene expression analyses may also help to design more individualized treatment approaches of cutaneous diseases.

*For a PDF of the full article, click on the link to the left of this introduction.

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

*For a PDF of the full article, click on the link to the left of this introduction.

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

*For a PDF of the full article, click on the link to the left of this introduction.

Mollie A. MacCormack, MD

Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Photodynamic therapy is a relatively new and rapidly evolving therapeutic option in dermatology. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease. Initially used for the treatment of actinic damage and nonmelanotic skin cancer, more recent work indicates efficacy in the treatment of a wide range of conditions, such as acne, infectious processes, cutaneous T-cell lymphoma, and photorejuvenation, among others. This article provides a comprehensive review of applications and outcomes that use topical photodynamic therapy in the treatment of dermatologic disease.

*For a PDF of the full article, click on the link to the left of this introduction.

SAN ANTONIO — A novel oral therapy with broad anti-inflammatory activity is showing promise for the treatment of moderate to severe plaque psoriasis, according to phase II study data presented at the annual meeting of the American Academy of Dermatology.

Apremilast (CC-10004, Celgene Corp.) is a phosphodiesterase type 4 inhibitor that has potent anti-inflammatory activity believed to result in part from inhibition of tumor necrosis factor-α and other proinflammatory mediators, including interleukin-2, interferon-α, leukotrienes, and nitric oxide synthase, Dr. Kim Papp of Probity Medical Research Inc., Waterloo, Ont., explained during a poster discussion session.

A group of 260 patients was enrolled in the randomized, controlled, 12-week trial, which compared once- and twice-daily 20-mg dosages of Apremilast with placebo. The study was supported by Celgene.

At week 12 of treatment, a significantly higher proportion of patients in the twice-daily treatment group achieved Psoriasis Activity and Severity Index-75 (PASI-75) scores, compared with the other groups (24% in the twice-daily treatment group versus 10% in the once-daily treatment and placebo groups). Similarly, PASI-50 scores were achieved by 57% of those in the twice-daily treatment group, 28% in the once-daily group, and 23% in the placebo group.

PASI-90 scores were achieved by 14% of patients in the twice-daily group, by 2% in the once-daily group, and by 6% in the placebo group, Dr. Papp said.

As for Dermatology Life Quality Index scores, the mean changes from baseline were 7 points among those treated twice daily, 5 points among those treated once daily, and 3 points among given placebo, he noted.

Patients in the treatment groups continued to show improvement over time, with the greatest mean percent reduction in PASI scores demonstrated at the final assessment at 12 weeks, he said.

Adverse events in the study were generally mild and were similar in all three groups. Fifty-four percent in the twice-daily treatment group, 68% in the once-daily group, and 60% in the placebo group reported at least one adverse event. Headache and nasopharyngitis were the most common adverse events in all three groups, followed by diarrhea, pruritus, fatigue, aggravated psoriasis, and nausea.

The participants in this phase II study were at least 18 years old, had a diagnosis of moderate to severe plaque psoriasis for at least 6 months prior to enrollment (but were otherwise in good health), had PASI scores of at least 10 and body surface area involvement of at least 10%, and were candidates for photo- or systemic therapy.

The findings demonstrate a favorable risk-benefit profile for Apremilast, Dr. Papp said.

"Current therapies are limited by toxicities or by lack of efficacy," he said, noting that very few available treatments are effective across the spectrum of psoriatic disease.

"We continue to seek novel and safe therapies for chronic plaque psoriasis … and this is the first [phosphodiesterase type 4 inhibitor] that has shown itself to be well tolerated, safe, and effective," he said.

SAN ANTONIO — A novel oral therapy with broad anti-inflammatory activity is showing promise for the treatment of moderate to severe plaque psoriasis, according to phase II study data presented at the annual meeting of the American Academy of Dermatology.

Apremilast (CC-10004, Celgene Corp.) is a phosphodiesterase type 4 inhibitor that has potent anti-inflammatory activity believed to result in part from inhibition of tumor necrosis factor-α and other proinflammatory mediators, including interleukin-2, interferon-α, leukotrienes, and nitric oxide synthase, Dr. Kim Papp of Probity Medical Research Inc., Waterloo, Ont., explained during a poster discussion session.

A group of 260 patients was enrolled in the randomized, controlled, 12-week trial, which compared once- and twice-daily 20-mg dosages of Apremilast with placebo. The study was supported by Celgene.

At week 12 of treatment, a significantly higher proportion of patients in the twice-daily treatment group achieved Psoriasis Activity and Severity Index-75 (PASI-75) scores, compared with the other groups (24% in the twice-daily treatment group versus 10% in the once-daily treatment and placebo groups). Similarly, PASI-50 scores were achieved by 57% of those in the twice-daily treatment group, 28% in the once-daily group, and 23% in the placebo group.

PASI-90 scores were achieved by 14% of patients in the twice-daily group, by 2% in the once-daily group, and by 6% in the placebo group, Dr. Papp said.

As for Dermatology Life Quality Index scores, the mean changes from baseline were 7 points among those treated twice daily, 5 points among those treated once daily, and 3 points among given placebo, he noted.

Patients in the treatment groups continued to show improvement over time, with the greatest mean percent reduction in PASI scores demonstrated at the final assessment at 12 weeks, he said.

Adverse events in the study were generally mild and were similar in all three groups. Fifty-four percent in the twice-daily treatment group, 68% in the once-daily group, and 60% in the placebo group reported at least one adverse event. Headache and nasopharyngitis were the most common adverse events in all three groups, followed by diarrhea, pruritus, fatigue, aggravated psoriasis, and nausea.

The participants in this phase II study were at least 18 years old, had a diagnosis of moderate to severe plaque psoriasis for at least 6 months prior to enrollment (but were otherwise in good health), had PASI scores of at least 10 and body surface area involvement of at least 10%, and were candidates for photo- or systemic therapy.

The findings demonstrate a favorable risk-benefit profile for Apremilast, Dr. Papp said.

"Current therapies are limited by toxicities or by lack of efficacy," he said, noting that very few available treatments are effective across the spectrum of psoriatic disease.

"We continue to seek novel and safe therapies for chronic plaque psoriasis … and this is the first [phosphodiesterase type 4 inhibitor] that has shown itself to be well tolerated, safe, and effective," he said.

SAN ANTONIO — A novel oral therapy with broad anti-inflammatory activity is showing promise for the treatment of moderate to severe plaque psoriasis, according to phase II study data presented at the annual meeting of the American Academy of Dermatology.

Apremilast (CC-10004, Celgene Corp.) is a phosphodiesterase type 4 inhibitor that has potent anti-inflammatory activity believed to result in part from inhibition of tumor necrosis factor-α and other proinflammatory mediators, including interleukin-2, interferon-α, leukotrienes, and nitric oxide synthase, Dr. Kim Papp of Probity Medical Research Inc., Waterloo, Ont., explained during a poster discussion session.

A group of 260 patients was enrolled in the randomized, controlled, 12-week trial, which compared once- and twice-daily 20-mg dosages of Apremilast with placebo. The study was supported by Celgene.

At week 12 of treatment, a significantly higher proportion of patients in the twice-daily treatment group achieved Psoriasis Activity and Severity Index-75 (PASI-75) scores, compared with the other groups (24% in the twice-daily treatment group versus 10% in the once-daily treatment and placebo groups). Similarly, PASI-50 scores were achieved by 57% of those in the twice-daily treatment group, 28% in the once-daily group, and 23% in the placebo group.

PASI-90 scores were achieved by 14% of patients in the twice-daily group, by 2% in the once-daily group, and by 6% in the placebo group, Dr. Papp said.

As for Dermatology Life Quality Index scores, the mean changes from baseline were 7 points among those treated twice daily, 5 points among those treated once daily, and 3 points among given placebo, he noted.

Patients in the treatment groups continued to show improvement over time, with the greatest mean percent reduction in PASI scores demonstrated at the final assessment at 12 weeks, he said.

Adverse events in the study were generally mild and were similar in all three groups. Fifty-four percent in the twice-daily treatment group, 68% in the once-daily group, and 60% in the placebo group reported at least one adverse event. Headache and nasopharyngitis were the most common adverse events in all three groups, followed by diarrhea, pruritus, fatigue, aggravated psoriasis, and nausea.

The participants in this phase II study were at least 18 years old, had a diagnosis of moderate to severe plaque psoriasis for at least 6 months prior to enrollment (but were otherwise in good health), had PASI scores of at least 10 and body surface area involvement of at least 10%, and were candidates for photo- or systemic therapy.

The findings demonstrate a favorable risk-benefit profile for Apremilast, Dr. Papp said.

"Current therapies are limited by toxicities or by lack of efficacy," he said, noting that very few available treatments are effective across the spectrum of psoriatic disease.

"We continue to seek novel and safe therapies for chronic plaque psoriasis … and this is the first [phosphodiesterase type 4 inhibitor] that has shown itself to be well tolerated, safe, and effective," he said.

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