Barbara J. Rutledge

In treating cosmetic dermatology patients for symptoms associated with aging, procedures are not enough, Dr. Leslie Baumann said in a Galderma-sponsored symposium held during the 21st World Congress of Dermatology in Buenos Aires.

"Skin care is also important," she said. "When you think about skin rejuvenation, you need to think about all components." Combination therapy is a key to treating aging-related skin problems.

In the epidermis, pigmentary therapy targets the melanocytes, and "barrier-restoring therapy" targets the keratinocytes. "Skin needs to be hydrated to look young," said Dr. Baumann, director of cosmetic dermatology at the University of Miami.

As skin ages, the levels of collagen and glycosaminoglycans in the dermis decrease and alterations in elastic tissue occur, she noted. Injection of hyaluronic acid or collagen fillers helps restore the structural integrity of the dermis. Vascular therapy prevents the enlargement of blood vessels in the dermis that is seen in the blushing associated with rosacea. Volume-restoring therapy targets the adipocytes in the subcutaneous tissue, and therapy that controls muscular movements, such as botulinum toxin, targets muscle fibers.

Retinoids prevent skin aging by increasing the production of collagen and hyaluronic acid. "You are doing your patients a disservice to give them botulinum toxin or fillers and not give them a retinoid," said Dr. Baumann.

Nearly half of the cosmetic dermatologists interviewed in a recent market survey acknowledged discussing makeup with their patients. Surprisingly, only a slightly higher percentage of those surveyed talked to their patients about the use of retinoids in skin rejuvenation. "If we are going to talk to our patients about how to look better, we need to tell them about the science," she said. Cosmetic dermatologists should explain to their patients the scientific basis underpinning the use of retinoids in skin rejuvenation.

Tolerability appears to be a problem. "We're just not seeing a lot of retinoid use. I think it is because retinoids cause redness and flaking, and patients don't want to use them," she said. "Doctors don't have time to explain to the patients how to use retinoids properly and how to get through that initial redness."

Dr. Baumann recommends the use of topical retinoids for treatment of photoaging, acne, pigmentation disorders such as melasma and solar lentigos, and rosacea. All retinoids that affect the retinoic acid receptor are thought to improve photoaging, but only tretinoin and Avage (tazarotene, Allergan) are approved by the Food and Drug Administration for the treatment of photoaging, she said.

Photoaging leads not just to wrinkles, but also to sunspots and pigmentary damage. In her own practice, Dr. Baumann uses Tri-Luma cream (fluocinolone acetonide/hydroquinone/tretinoin, Galderma) off label for treatment of photoaging.

"I use retinoids in rosacea patients," she said. "I know you've been taught not to, but I put all my rosacea patients on retinoids. I can do it by teaching them how to use the retinoids properly."

Dr. Baumann is an investigator for Galderma and other manufacturers of skin care products.

In treating cosmetic dermatology patients for symptoms associated with aging, procedures are not enough, Dr. Leslie Baumann said in a Galderma-sponsored symposium held during the 21st World Congress of Dermatology in Buenos Aires.

"Skin care is also important," she said. "When you think about skin rejuvenation, you need to think about all components." Combination therapy is a key to treating aging-related skin problems.

In the epidermis, pigmentary therapy targets the melanocytes, and "barrier-restoring therapy" targets the keratinocytes. "Skin needs to be hydrated to look young," said Dr. Baumann, director of cosmetic dermatology at the University of Miami.

As skin ages, the levels of collagen and glycosaminoglycans in the dermis decrease and alterations in elastic tissue occur, she noted. Injection of hyaluronic acid or collagen fillers helps restore the structural integrity of the dermis. Vascular therapy prevents the enlargement of blood vessels in the dermis that is seen in the blushing associated with rosacea. Volume-restoring therapy targets the adipocytes in the subcutaneous tissue, and therapy that controls muscular movements, such as botulinum toxin, targets muscle fibers.

Retinoids prevent skin aging by increasing the production of collagen and hyaluronic acid. "You are doing your patients a disservice to give them botulinum toxin or fillers and not give them a retinoid," said Dr. Baumann.

Nearly half of the cosmetic dermatologists interviewed in a recent market survey acknowledged discussing makeup with their patients. Surprisingly, only a slightly higher percentage of those surveyed talked to their patients about the use of retinoids in skin rejuvenation. "If we are going to talk to our patients about how to look better, we need to tell them about the science," she said. Cosmetic dermatologists should explain to their patients the scientific basis underpinning the use of retinoids in skin rejuvenation.

Tolerability appears to be a problem. "We're just not seeing a lot of retinoid use. I think it is because retinoids cause redness and flaking, and patients don't want to use them," she said. "Doctors don't have time to explain to the patients how to use retinoids properly and how to get through that initial redness."

Dr. Baumann recommends the use of topical retinoids for treatment of photoaging, acne, pigmentation disorders such as melasma and solar lentigos, and rosacea. All retinoids that affect the retinoic acid receptor are thought to improve photoaging, but only tretinoin and Avage (tazarotene, Allergan) are approved by the Food and Drug Administration for the treatment of photoaging, she said.

Photoaging leads not just to wrinkles, but also to sunspots and pigmentary damage. In her own practice, Dr. Baumann uses Tri-Luma cream (fluocinolone acetonide/hydroquinone/tretinoin, Galderma) off label for treatment of photoaging.

"I use retinoids in rosacea patients," she said. "I know you've been taught not to, but I put all my rosacea patients on retinoids. I can do it by teaching them how to use the retinoids properly."

Dr. Baumann is an investigator for Galderma and other manufacturers of skin care products.

In treating cosmetic dermatology patients for symptoms associated with aging, procedures are not enough, Dr. Leslie Baumann said in a Galderma-sponsored symposium held during the 21st World Congress of Dermatology in Buenos Aires.

"Skin care is also important," she said. "When you think about skin rejuvenation, you need to think about all components." Combination therapy is a key to treating aging-related skin problems.

In the epidermis, pigmentary therapy targets the melanocytes, and "barrier-restoring therapy" targets the keratinocytes. "Skin needs to be hydrated to look young," said Dr. Baumann, director of cosmetic dermatology at the University of Miami.

As skin ages, the levels of collagen and glycosaminoglycans in the dermis decrease and alterations in elastic tissue occur, she noted. Injection of hyaluronic acid or collagen fillers helps restore the structural integrity of the dermis. Vascular therapy prevents the enlargement of blood vessels in the dermis that is seen in the blushing associated with rosacea. Volume-restoring therapy targets the adipocytes in the subcutaneous tissue, and therapy that controls muscular movements, such as botulinum toxin, targets muscle fibers.

Retinoids prevent skin aging by increasing the production of collagen and hyaluronic acid. "You are doing your patients a disservice to give them botulinum toxin or fillers and not give them a retinoid," said Dr. Baumann.

Nearly half of the cosmetic dermatologists interviewed in a recent market survey acknowledged discussing makeup with their patients. Surprisingly, only a slightly higher percentage of those surveyed talked to their patients about the use of retinoids in skin rejuvenation. "If we are going to talk to our patients about how to look better, we need to tell them about the science," she said. Cosmetic dermatologists should explain to their patients the scientific basis underpinning the use of retinoids in skin rejuvenation.

Tolerability appears to be a problem. "We're just not seeing a lot of retinoid use. I think it is because retinoids cause redness and flaking, and patients don't want to use them," she said. "Doctors don't have time to explain to the patients how to use retinoids properly and how to get through that initial redness."

Dr. Baumann recommends the use of topical retinoids for treatment of photoaging, acne, pigmentation disorders such as melasma and solar lentigos, and rosacea. All retinoids that affect the retinoic acid receptor are thought to improve photoaging, but only tretinoin and Avage (tazarotene, Allergan) are approved by the Food and Drug Administration for the treatment of photoaging, she said.

Photoaging leads not just to wrinkles, but also to sunspots and pigmentary damage. In her own practice, Dr. Baumann uses Tri-Luma cream (fluocinolone acetonide/hydroquinone/tretinoin, Galderma) off label for treatment of photoaging.

"I use retinoids in rosacea patients," she said. "I know you've been taught not to, but I put all my rosacea patients on retinoids. I can do it by teaching them how to use the retinoids properly."

Dr. Baumann is an investigator for Galderma and other manufacturers of skin care products.

BUENOS AIRES — A positive test for antineutrophil cytoplasmic antibody may be associated with a vasculitis of the skin, but the test is usually not specific, so patients with other diseases may test positive, Dr. Jeffrey Callen said at the 21st World Congress of Dermatology.

To support a diagnosis of one of the ANCA-associated vasculitides, a positive ANCA test should be correlated with other clinical symptoms. “Skin disease is a relatively common feature in ANCA-associated vasculitis and can be an initial manifestation,” said Dr. Callen of the University of Louisville (Ky.).

ANCA-associated vasculitis affects small- to medium-sized vessels. The traditional ANCA-associated vasculitides are Wegener's granulomatosis, microscopic polyarteritis, and Churg-Strauss syndrome. Wegener's granulomatosis and microscopic polyarteritis are both characterized by pauci-immune necrotizing vasculitis with crescentic glomerulonephritis and pulmonary capillaritis. A significant difference between the two is the presence of granulomas in Wegener's patients.

Churg-Strauss syndrome is a systemic vasculitis often tied to eosinophilia, allergic rhinitis, and asthma. Drug-induced vasculitides, like minocycline-induced disease, are also sometimes ANCA positive, he said.

ANCAs are autoimmune antibodies directed against antigens in the cytoplasmic granules of neutrophils and monocytes. Most are IgG associated. They are grouped according to histochemical staining: cytoplasmic-ANCA (c-ANCA) and perinuclear-ANCA (p-ANCA). C-ANCA against proteinase 3 is specific for Wegener's. One of the major p-ANCAs, directed against myeloperoxidase, is seen in microscopic polyarteritis but is also found in ulcerative colitis, Sweet's syndrome, propylthiouracil-induced vasculitis, and minocycline-induced vasculitis, said Dr. Callen.

Skin lesions, primarily ulcerations and palpable purpura, are a common feature of microscopic polyarteritis, and cutaneous manifestations have been reported in up to 70% of patients with Churg-Strauss syndrome. Skin lesions in Churg-Strauss include subcutaneous nodules and macular or papular erythema or urticaria, but the most common is palpable purpura, seen in about half of the patients who have cutaneous manifestations. Other possible cutaneous manifestations include ulceration and livedo reticularis. A Churg-Strauss granuloma on the skin is quite rare but highly specific, Dr. Callen said.

In a review of 90 patients with Churg-Strauss syndrome at the Mayo Clinic between 1976 and 1995, investigators found 36 (40%) had cutaneous manifestations (J. Am. Acad. Dermatol. 1997;37:199-203), most frequently purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows.

Wegener's granulomatosis skin lesions are similar to those in Churg-Strauss syndrome. In addition, pyoderma gangrenosum-like lesions can occur in Wegener's. A recent report described cutaneous manifestations of Wegener's in 17 patients (J. Cutan. Pathol. 2007;34:739-47). Three had skin disease before systemic disease; one patient's ANCA test was initially negative. Six had concurrent onset of skin and systemic disease, and eight developed skin disease after systemic disease was diagnosed.

In a meta-analysis (JAMA 2007;298:655-69), patients with localized disease were recommended an antibiotic like cotrimoxazole, with or without corticosteroids. Methotrexate plus corticosteroids was recommended for generalized, non-organ-threatening disease and pulse cyclophosphamide plus corticosteroids was touted for patients with generalized, organ-threatening disease. For severe renal vasculitis, plasma exchange might also be included. High-dose cyclophosphamide plus pulse methylprednisolone was recommended for diffuse pulmonary hemorrhage, possibly with plasma exchange.

Dr. Callen has consulted for and accepted speaker fees from several makers of biologics used in rheumatic diseases.

BUENOS AIRES — A positive test for antineutrophil cytoplasmic antibody may be associated with a vasculitis of the skin, but the test is usually not specific, so patients with other diseases may test positive, Dr. Jeffrey Callen said at the 21st World Congress of Dermatology.

To support a diagnosis of one of the ANCA-associated vasculitides, a positive ANCA test should be correlated with other clinical symptoms. “Skin disease is a relatively common feature in ANCA-associated vasculitis and can be an initial manifestation,” said Dr. Callen of the University of Louisville (Ky.).

ANCA-associated vasculitis affects small- to medium-sized vessels. The traditional ANCA-associated vasculitides are Wegener's granulomatosis, microscopic polyarteritis, and Churg-Strauss syndrome. Wegener's granulomatosis and microscopic polyarteritis are both characterized by pauci-immune necrotizing vasculitis with crescentic glomerulonephritis and pulmonary capillaritis. A significant difference between the two is the presence of granulomas in Wegener's patients.

Churg-Strauss syndrome is a systemic vasculitis often tied to eosinophilia, allergic rhinitis, and asthma. Drug-induced vasculitides, like minocycline-induced disease, are also sometimes ANCA positive, he said.

ANCAs are autoimmune antibodies directed against antigens in the cytoplasmic granules of neutrophils and monocytes. Most are IgG associated. They are grouped according to histochemical staining: cytoplasmic-ANCA (c-ANCA) and perinuclear-ANCA (p-ANCA). C-ANCA against proteinase 3 is specific for Wegener's. One of the major p-ANCAs, directed against myeloperoxidase, is seen in microscopic polyarteritis but is also found in ulcerative colitis, Sweet's syndrome, propylthiouracil-induced vasculitis, and minocycline-induced vasculitis, said Dr. Callen.

Skin lesions, primarily ulcerations and palpable purpura, are a common feature of microscopic polyarteritis, and cutaneous manifestations have been reported in up to 70% of patients with Churg-Strauss syndrome. Skin lesions in Churg-Strauss include subcutaneous nodules and macular or papular erythema or urticaria, but the most common is palpable purpura, seen in about half of the patients who have cutaneous manifestations. Other possible cutaneous manifestations include ulceration and livedo reticularis. A Churg-Strauss granuloma on the skin is quite rare but highly specific, Dr. Callen said.

In a review of 90 patients with Churg-Strauss syndrome at the Mayo Clinic between 1976 and 1995, investigators found 36 (40%) had cutaneous manifestations (J. Am. Acad. Dermatol. 1997;37:199-203), most frequently purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows.

Wegener's granulomatosis skin lesions are similar to those in Churg-Strauss syndrome. In addition, pyoderma gangrenosum-like lesions can occur in Wegener's. A recent report described cutaneous manifestations of Wegener's in 17 patients (J. Cutan. Pathol. 2007;34:739-47). Three had skin disease before systemic disease; one patient's ANCA test was initially negative. Six had concurrent onset of skin and systemic disease, and eight developed skin disease after systemic disease was diagnosed.

In a meta-analysis (JAMA 2007;298:655-69), patients with localized disease were recommended an antibiotic like cotrimoxazole, with or without corticosteroids. Methotrexate plus corticosteroids was recommended for generalized, non-organ-threatening disease and pulse cyclophosphamide plus corticosteroids was touted for patients with generalized, organ-threatening disease. For severe renal vasculitis, plasma exchange might also be included. High-dose cyclophosphamide plus pulse methylprednisolone was recommended for diffuse pulmonary hemorrhage, possibly with plasma exchange.

Dr. Callen has consulted for and accepted speaker fees from several makers of biologics used in rheumatic diseases.

BUENOS AIRES — A positive test for antineutrophil cytoplasmic antibody may be associated with a vasculitis of the skin, but the test is usually not specific, so patients with other diseases may test positive, Dr. Jeffrey Callen said at the 21st World Congress of Dermatology.

To support a diagnosis of one of the ANCA-associated vasculitides, a positive ANCA test should be correlated with other clinical symptoms. “Skin disease is a relatively common feature in ANCA-associated vasculitis and can be an initial manifestation,” said Dr. Callen of the University of Louisville (Ky.).

ANCA-associated vasculitis affects small- to medium-sized vessels. The traditional ANCA-associated vasculitides are Wegener's granulomatosis, microscopic polyarteritis, and Churg-Strauss syndrome. Wegener's granulomatosis and microscopic polyarteritis are both characterized by pauci-immune necrotizing vasculitis with crescentic glomerulonephritis and pulmonary capillaritis. A significant difference between the two is the presence of granulomas in Wegener's patients.

Churg-Strauss syndrome is a systemic vasculitis often tied to eosinophilia, allergic rhinitis, and asthma. Drug-induced vasculitides, like minocycline-induced disease, are also sometimes ANCA positive, he said.

ANCAs are autoimmune antibodies directed against antigens in the cytoplasmic granules of neutrophils and monocytes. Most are IgG associated. They are grouped according to histochemical staining: cytoplasmic-ANCA (c-ANCA) and perinuclear-ANCA (p-ANCA). C-ANCA against proteinase 3 is specific for Wegener's. One of the major p-ANCAs, directed against myeloperoxidase, is seen in microscopic polyarteritis but is also found in ulcerative colitis, Sweet's syndrome, propylthiouracil-induced vasculitis, and minocycline-induced vasculitis, said Dr. Callen.

Skin lesions, primarily ulcerations and palpable purpura, are a common feature of microscopic polyarteritis, and cutaneous manifestations have been reported in up to 70% of patients with Churg-Strauss syndrome. Skin lesions in Churg-Strauss include subcutaneous nodules and macular or papular erythema or urticaria, but the most common is palpable purpura, seen in about half of the patients who have cutaneous manifestations. Other possible cutaneous manifestations include ulceration and livedo reticularis. A Churg-Strauss granuloma on the skin is quite rare but highly specific, Dr. Callen said.

In a review of 90 patients with Churg-Strauss syndrome at the Mayo Clinic between 1976 and 1995, investigators found 36 (40%) had cutaneous manifestations (J. Am. Acad. Dermatol. 1997;37:199-203), most frequently purpura and petechiae on the lower extremities and cutaneous nodules and papules on the elbows.

Wegener's granulomatosis skin lesions are similar to those in Churg-Strauss syndrome. In addition, pyoderma gangrenosum-like lesions can occur in Wegener's. A recent report described cutaneous manifestations of Wegener's in 17 patients (J. Cutan. Pathol. 2007;34:739-47). Three had skin disease before systemic disease; one patient's ANCA test was initially negative. Six had concurrent onset of skin and systemic disease, and eight developed skin disease after systemic disease was diagnosed.

In a meta-analysis (JAMA 2007;298:655-69), patients with localized disease were recommended an antibiotic like cotrimoxazole, with or without corticosteroids. Methotrexate plus corticosteroids was recommended for generalized, non-organ-threatening disease and pulse cyclophosphamide plus corticosteroids was touted for patients with generalized, organ-threatening disease. For severe renal vasculitis, plasma exchange might also be included. High-dose cyclophosphamide plus pulse methylprednisolone was recommended for diffuse pulmonary hemorrhage, possibly with plasma exchange.

Dr. Callen has consulted for and accepted speaker fees from several makers of biologics used in rheumatic diseases.

BUENOS AIRES — The successful treatment of melanoma in the future is likely to be a two-step process involving combination therapy, Meenhard Herlyn, D.Sc., said in a keynote address at the 21st World Congress of Dermatology.

The aim of the initial treatment will be to debulk the tumor from the major transit-amplifying cells. The second stage will then be to focus on eradication of the cancer stem cells.

"If you do not eliminate these tumor stem cells with therapy, the tumor will come back over and over again," said Dr. Herlyn, professor and program leader in the molecular and cellular oncogenesis program at the Wistar Institute, Philadelphia.

Melanoma arises from malignant transformation of melanocytes or nevus cells, which are formed by overproliferation of melanocytes. Progression from nevi occurs in approximately 50% of melanomas. In normal skin, keratinocytes control the growth of melanocytes in a sort of master-slave relationship.

The decoupling of melanocytes from keratinocytes is the first step in the development of nevi. Overproduction of growth factors from fibroblasts then drives melanocyte proliferation, Dr. Herlyn explained.

For development of melanoma, the most important pathway is the mitogen-activated protein (MAP) kinase pathway, he said.

A genomewide screen performed at the Wellcome Trust Sanger Institute showed that approximately two-thirds of melanomas harbor an activating mutation in BRAF, one of the Raf isoforms in the MAP kinase pathway (Nature 2002;417:949–54).

In 98% of these cases, the BRAF mutation is V600E. A single mutation, however, is not sufficient for the development of melanoma.

Mutations in other signaling pathways, such as the P13-kinase/Akt pathways or cell cycle regulatory pathways, have also been implicated in the development of melanoma, said Dr. Herlyn, who reported no conflicts of interest.

Earlier models of cancer development assumed that melanoma arose as the accumulation of sequential mutations in a mature, differentiated melanocyte eventually leading to malignant transformation of the cell. Identification of another type of cell in melanomas, however, suggests that this model may be too simplistic.

"There are rare cells in tumors that act like stem cells and always replenish the tumor with new cells," said Dr. Herlyn.

The cell that undergoes malignant transformation to produce melanoma might not be a terminally differentiated cell, but instead might be a type of stem cell.

When they are grown under conditions suitable for embryonic stem cells, melanoma cells form spheres that look similar to embryoid bodies formed by human stem cells (Cancer Res. 2005;65:9328–37).

These melanoma spheres meet the definition of tumor stem cells. Melanoma spheres are capable of self-renewal. The cells are highly tumorigenic and quickly form lethal melanomas when injected into nude mice.

They also are multipotent—under laboratory conditions, melanoma spheres can differentiate into melanocytes, adipocytes, chondrocytes, and osteoblasts.

"There is an incredible plasticity in melanoma cells that we have not known before," said Dr. Herlyn. "The question is: What is the true melanoma stem cell?"

Melanoma spheres consist of a mixed cell population. Among the population are cells expressing the hematopoietic marker CD20 and cells expressing the embryonic stem cell marker CD133. Melanoma spheres include side population cells that extrude Hoechst dye via active efflux.

Particularly intriguing are the label-retaining melanoma cells, which proliferate slowly or not at all. When removed from the surrounding cells, however, the label-retaining cells begin to divide rapidly. "If you isolate them, they literally explode," he said.

The label-retaining cells may be the melanoma stem cells, responsible for tumor dormancy and relapse. In this model, the CD20 cells, the CD133 cells, and the side population cells function as progenitor cells.

The label-retaining cells and the progenitor cells could give rise to transit-amplifying cells, Dr. Herlyn suggested at the meeting.

Melanomas are phenotypically heterogeneous tumors. "Tumor heterogeneity is not random," he noted. "Tumor heterogeneity represents a clonal hierarchy in which the different populations compete with each other."

In the center of the hierarchy is the melanoma stem cell. Although melanomas may differ from one patient to the next, they all contain melanoma stem cells. Targeting the stem cell is critical for treatment outcome. "This one cell can give rise to all the others," said Dr. Herlyn. "If we let the cancer stem cell escape, we will always get the cancer back."

Under suitable conditions, melanoma cells form spheres (shown here at 40X magnification) that are capable of self-renewal and are highly tumorigenic. Courtesy Meenhard Herlyn, D.Sc.

'This one cell can give rise to all the others. If we let the cancer stem cell escape, we will always get the cancer back.' DR. HERLYN

BUENOS AIRES — The successful treatment of melanoma in the future is likely to be a two-step process involving combination therapy, Meenhard Herlyn, D.Sc., said in a keynote address at the 21st World Congress of Dermatology.

The aim of the initial treatment will be to debulk the tumor from the major transit-amplifying cells. The second stage will then be to focus on eradication of the cancer stem cells.

"If you do not eliminate these tumor stem cells with therapy, the tumor will come back over and over again," said Dr. Herlyn, professor and program leader in the molecular and cellular oncogenesis program at the Wistar Institute, Philadelphia.

Melanoma arises from malignant transformation of melanocytes or nevus cells, which are formed by overproliferation of melanocytes. Progression from nevi occurs in approximately 50% of melanomas. In normal skin, keratinocytes control the growth of melanocytes in a sort of master-slave relationship.

The decoupling of melanocytes from keratinocytes is the first step in the development of nevi. Overproduction of growth factors from fibroblasts then drives melanocyte proliferation, Dr. Herlyn explained.

For development of melanoma, the most important pathway is the mitogen-activated protein (MAP) kinase pathway, he said.

A genomewide screen performed at the Wellcome Trust Sanger Institute showed that approximately two-thirds of melanomas harbor an activating mutation in BRAF, one of the Raf isoforms in the MAP kinase pathway (Nature 2002;417:949–54).

In 98% of these cases, the BRAF mutation is V600E. A single mutation, however, is not sufficient for the development of melanoma.

Mutations in other signaling pathways, such as the P13-kinase/Akt pathways or cell cycle regulatory pathways, have also been implicated in the development of melanoma, said Dr. Herlyn, who reported no conflicts of interest.

Earlier models of cancer development assumed that melanoma arose as the accumulation of sequential mutations in a mature, differentiated melanocyte eventually leading to malignant transformation of the cell. Identification of another type of cell in melanomas, however, suggests that this model may be too simplistic.

"There are rare cells in tumors that act like stem cells and always replenish the tumor with new cells," said Dr. Herlyn.

The cell that undergoes malignant transformation to produce melanoma might not be a terminally differentiated cell, but instead might be a type of stem cell.

When they are grown under conditions suitable for embryonic stem cells, melanoma cells form spheres that look similar to embryoid bodies formed by human stem cells (Cancer Res. 2005;65:9328–37).

These melanoma spheres meet the definition of tumor stem cells. Melanoma spheres are capable of self-renewal. The cells are highly tumorigenic and quickly form lethal melanomas when injected into nude mice.

They also are multipotent—under laboratory conditions, melanoma spheres can differentiate into melanocytes, adipocytes, chondrocytes, and osteoblasts.

"There is an incredible plasticity in melanoma cells that we have not known before," said Dr. Herlyn. "The question is: What is the true melanoma stem cell?"

Melanoma spheres consist of a mixed cell population. Among the population are cells expressing the hematopoietic marker CD20 and cells expressing the embryonic stem cell marker CD133. Melanoma spheres include side population cells that extrude Hoechst dye via active efflux.

Particularly intriguing are the label-retaining melanoma cells, which proliferate slowly or not at all. When removed from the surrounding cells, however, the label-retaining cells begin to divide rapidly. "If you isolate them, they literally explode," he said.

The label-retaining cells may be the melanoma stem cells, responsible for tumor dormancy and relapse. In this model, the CD20 cells, the CD133 cells, and the side population cells function as progenitor cells.

The label-retaining cells and the progenitor cells could give rise to transit-amplifying cells, Dr. Herlyn suggested at the meeting.

Melanomas are phenotypically heterogeneous tumors. "Tumor heterogeneity is not random," he noted. "Tumor heterogeneity represents a clonal hierarchy in which the different populations compete with each other."

In the center of the hierarchy is the melanoma stem cell. Although melanomas may differ from one patient to the next, they all contain melanoma stem cells. Targeting the stem cell is critical for treatment outcome. "This one cell can give rise to all the others," said Dr. Herlyn. "If we let the cancer stem cell escape, we will always get the cancer back."

Under suitable conditions, melanoma cells form spheres (shown here at 40X magnification) that are capable of self-renewal and are highly tumorigenic. Courtesy Meenhard Herlyn, D.Sc.

'This one cell can give rise to all the others. If we let the cancer stem cell escape, we will always get the cancer back.' DR. HERLYN

BUENOS AIRES — The successful treatment of melanoma in the future is likely to be a two-step process involving combination therapy, Meenhard Herlyn, D.Sc., said in a keynote address at the 21st World Congress of Dermatology.

The aim of the initial treatment will be to debulk the tumor from the major transit-amplifying cells. The second stage will then be to focus on eradication of the cancer stem cells.

"If you do not eliminate these tumor stem cells with therapy, the tumor will come back over and over again," said Dr. Herlyn, professor and program leader in the molecular and cellular oncogenesis program at the Wistar Institute, Philadelphia.

Melanoma arises from malignant transformation of melanocytes or nevus cells, which are formed by overproliferation of melanocytes. Progression from nevi occurs in approximately 50% of melanomas. In normal skin, keratinocytes control the growth of melanocytes in a sort of master-slave relationship.

The decoupling of melanocytes from keratinocytes is the first step in the development of nevi. Overproduction of growth factors from fibroblasts then drives melanocyte proliferation, Dr. Herlyn explained.

For development of melanoma, the most important pathway is the mitogen-activated protein (MAP) kinase pathway, he said.

A genomewide screen performed at the Wellcome Trust Sanger Institute showed that approximately two-thirds of melanomas harbor an activating mutation in BRAF, one of the Raf isoforms in the MAP kinase pathway (Nature 2002;417:949–54).

In 98% of these cases, the BRAF mutation is V600E. A single mutation, however, is not sufficient for the development of melanoma.

Mutations in other signaling pathways, such as the P13-kinase/Akt pathways or cell cycle regulatory pathways, have also been implicated in the development of melanoma, said Dr. Herlyn, who reported no conflicts of interest.

Earlier models of cancer development assumed that melanoma arose as the accumulation of sequential mutations in a mature, differentiated melanocyte eventually leading to malignant transformation of the cell. Identification of another type of cell in melanomas, however, suggests that this model may be too simplistic.

"There are rare cells in tumors that act like stem cells and always replenish the tumor with new cells," said Dr. Herlyn.

The cell that undergoes malignant transformation to produce melanoma might not be a terminally differentiated cell, but instead might be a type of stem cell.

When they are grown under conditions suitable for embryonic stem cells, melanoma cells form spheres that look similar to embryoid bodies formed by human stem cells (Cancer Res. 2005;65:9328–37).

These melanoma spheres meet the definition of tumor stem cells. Melanoma spheres are capable of self-renewal. The cells are highly tumorigenic and quickly form lethal melanomas when injected into nude mice.

They also are multipotent—under laboratory conditions, melanoma spheres can differentiate into melanocytes, adipocytes, chondrocytes, and osteoblasts.

"There is an incredible plasticity in melanoma cells that we have not known before," said Dr. Herlyn. "The question is: What is the true melanoma stem cell?"

Melanoma spheres consist of a mixed cell population. Among the population are cells expressing the hematopoietic marker CD20 and cells expressing the embryonic stem cell marker CD133. Melanoma spheres include side population cells that extrude Hoechst dye via active efflux.

Particularly intriguing are the label-retaining melanoma cells, which proliferate slowly or not at all. When removed from the surrounding cells, however, the label-retaining cells begin to divide rapidly. "If you isolate them, they literally explode," he said.

The label-retaining cells may be the melanoma stem cells, responsible for tumor dormancy and relapse. In this model, the CD20 cells, the CD133 cells, and the side population cells function as progenitor cells.

The label-retaining cells and the progenitor cells could give rise to transit-amplifying cells, Dr. Herlyn suggested at the meeting.

Melanomas are phenotypically heterogeneous tumors. "Tumor heterogeneity is not random," he noted. "Tumor heterogeneity represents a clonal hierarchy in which the different populations compete with each other."

In the center of the hierarchy is the melanoma stem cell. Although melanomas may differ from one patient to the next, they all contain melanoma stem cells. Targeting the stem cell is critical for treatment outcome. "This one cell can give rise to all the others," said Dr. Herlyn. "If we let the cancer stem cell escape, we will always get the cancer back."

Under suitable conditions, melanoma cells form spheres (shown here at 40X magnification) that are capable of self-renewal and are highly tumorigenic. Courtesy Meenhard Herlyn, D.Sc.

'This one cell can give rise to all the others. If we let the cancer stem cell escape, we will always get the cancer back.' DR. HERLYN

BUENOS AIRES — Cultural sensitivity is essential for dermatologists who work with Hispanic and Latino patients, Dr. David Rodriguez said at the 21st World Congress of Dermatology.

"Many immigrants continue to adhere to their cultural views of health and disease," he said. Failure to understand cultural background leads to miscommunication in the doctor-patient relationship and can result in poor treatment compliance.

Approximately 42 million people in the United States are ethnically identified as Hispanic. The term Hispanic came into widespread use in the United States in the 1970s, when it was first used as a classification in the national census. Hispanic refers to someone of Spanish descent, and in the United States it is a governmental designation of ethnicity. Latino refers to the Latin-based or Romance languages.

"When you say Latino, you would include the people of Portugal and Brazil," said Dr. Rodriguez, a dermatologist in Coral Gables, Fla. "When you say Hispanic, you talk about the people who come from Spain." The terms, however, are often used interchangeably.

The Hispanic population is racially diverse. Hispanics can be white, black, American Indian, or a mixture of racial groups. "The Hispanic population is also culturally diverse. When we look at Hispanics we cannot think of them as just one group," he said. "There are great differences between someone from Argentina, and what he or she does, and someone from El Salvador." Understanding the cultural proclivities for each patient is important.

Cultural differences that might impede care of Hispanic patients include reluctance to question the physician, who may be seen as an authority figure, and hesitation to discuss their disease because of embarrassment. Cultural belief in fatalismo also can impede treatment: Patients might accept their condition as the will of God and feel powerless to change it.

Acne, eczema/contact dermatitis, photoaging, facial melasma, and hyperpigmentation are the major dermatologic conditions seen in Hispanic patients in private clinics. Disorders of pigmentation are especially important to Hispanic patients because they consider them disfiguring.

Conditions like melasma or acne can have a profoundly negative impact on self-esteem, quality of life, and job pros-pects, said Dr. Rodriguez.

Melasma is common in Hispanics, particularly in women. "Hispanics commonly attribute melasma to a sick liver, aging, poor nutrition, or lack of sleep," he said, so patients need to understand the role of UV radiation in triggering or exacerbating the condition.

Special care must be taken in treating acne in Hispanic patients because Fitzpatrick skin types IV-VI are susceptible to hyperpigmentation. Hispanic patients are often unaware that they have acne, but they may be concerned about "dark scars or spots," said Dr. Rodriguez. "We must educate them that they have to stop touching or picking their face."

Like other patient populations, Hispanics have misconceptions about the causes of acne, and may attribute outbreaks of acne to certain foods, sex, or ill health. They need to know that the ointments and oils, especially cocoa butter, in popular Hispanic hair and skin treatments can clog pores and worsen acne, he said.

There is a widespread misconception that individuals with dark pigmented skin cannot get skin cancer, so many Hispanics consider sunscreens necessary only for the beach or the pool and do not understand the importance of using sunscreen on a daily basis. Dr. Rodriguez said he recommends that Hispanic patients be reminded to use sunscreen, particularly in regions of the country, such as South Florida, where incidental sun exposure can be intense.

Ideally, dermatologists who treat Hispanic patients should provide Spanish-language materials in the waiting room and offer bilingual take-home instructions. Practices that treat many Hispanic patients should have a bilingual staff, he said.

BUENOS AIRES — Cultural sensitivity is essential for dermatologists who work with Hispanic and Latino patients, Dr. David Rodriguez said at the 21st World Congress of Dermatology.

"Many immigrants continue to adhere to their cultural views of health and disease," he said. Failure to understand cultural background leads to miscommunication in the doctor-patient relationship and can result in poor treatment compliance.

Approximately 42 million people in the United States are ethnically identified as Hispanic. The term Hispanic came into widespread use in the United States in the 1970s, when it was first used as a classification in the national census. Hispanic refers to someone of Spanish descent, and in the United States it is a governmental designation of ethnicity. Latino refers to the Latin-based or Romance languages.

"When you say Latino, you would include the people of Portugal and Brazil," said Dr. Rodriguez, a dermatologist in Coral Gables, Fla. "When you say Hispanic, you talk about the people who come from Spain." The terms, however, are often used interchangeably.

The Hispanic population is racially diverse. Hispanics can be white, black, American Indian, or a mixture of racial groups. "The Hispanic population is also culturally diverse. When we look at Hispanics we cannot think of them as just one group," he said. "There are great differences between someone from Argentina, and what he or she does, and someone from El Salvador." Understanding the cultural proclivities for each patient is important.

Cultural differences that might impede care of Hispanic patients include reluctance to question the physician, who may be seen as an authority figure, and hesitation to discuss their disease because of embarrassment. Cultural belief in fatalismo also can impede treatment: Patients might accept their condition as the will of God and feel powerless to change it.

Acne, eczema/contact dermatitis, photoaging, facial melasma, and hyperpigmentation are the major dermatologic conditions seen in Hispanic patients in private clinics. Disorders of pigmentation are especially important to Hispanic patients because they consider them disfiguring.

Conditions like melasma or acne can have a profoundly negative impact on self-esteem, quality of life, and job pros-pects, said Dr. Rodriguez.

Melasma is common in Hispanics, particularly in women. "Hispanics commonly attribute melasma to a sick liver, aging, poor nutrition, or lack of sleep," he said, so patients need to understand the role of UV radiation in triggering or exacerbating the condition.

Special care must be taken in treating acne in Hispanic patients because Fitzpatrick skin types IV-VI are susceptible to hyperpigmentation. Hispanic patients are often unaware that they have acne, but they may be concerned about "dark scars or spots," said Dr. Rodriguez. "We must educate them that they have to stop touching or picking their face."

Like other patient populations, Hispanics have misconceptions about the causes of acne, and may attribute outbreaks of acne to certain foods, sex, or ill health. They need to know that the ointments and oils, especially cocoa butter, in popular Hispanic hair and skin treatments can clog pores and worsen acne, he said.

There is a widespread misconception that individuals with dark pigmented skin cannot get skin cancer, so many Hispanics consider sunscreens necessary only for the beach or the pool and do not understand the importance of using sunscreen on a daily basis. Dr. Rodriguez said he recommends that Hispanic patients be reminded to use sunscreen, particularly in regions of the country, such as South Florida, where incidental sun exposure can be intense.

Ideally, dermatologists who treat Hispanic patients should provide Spanish-language materials in the waiting room and offer bilingual take-home instructions. Practices that treat many Hispanic patients should have a bilingual staff, he said.

BUENOS AIRES — Cultural sensitivity is essential for dermatologists who work with Hispanic and Latino patients, Dr. David Rodriguez said at the 21st World Congress of Dermatology.

"Many immigrants continue to adhere to their cultural views of health and disease," he said. Failure to understand cultural background leads to miscommunication in the doctor-patient relationship and can result in poor treatment compliance.

Approximately 42 million people in the United States are ethnically identified as Hispanic. The term Hispanic came into widespread use in the United States in the 1970s, when it was first used as a classification in the national census. Hispanic refers to someone of Spanish descent, and in the United States it is a governmental designation of ethnicity. Latino refers to the Latin-based or Romance languages.

"When you say Latino, you would include the people of Portugal and Brazil," said Dr. Rodriguez, a dermatologist in Coral Gables, Fla. "When you say Hispanic, you talk about the people who come from Spain." The terms, however, are often used interchangeably.

The Hispanic population is racially diverse. Hispanics can be white, black, American Indian, or a mixture of racial groups. "The Hispanic population is also culturally diverse. When we look at Hispanics we cannot think of them as just one group," he said. "There are great differences between someone from Argentina, and what he or she does, and someone from El Salvador." Understanding the cultural proclivities for each patient is important.

Cultural differences that might impede care of Hispanic patients include reluctance to question the physician, who may be seen as an authority figure, and hesitation to discuss their disease because of embarrassment. Cultural belief in fatalismo also can impede treatment: Patients might accept their condition as the will of God and feel powerless to change it.

Acne, eczema/contact dermatitis, photoaging, facial melasma, and hyperpigmentation are the major dermatologic conditions seen in Hispanic patients in private clinics. Disorders of pigmentation are especially important to Hispanic patients because they consider them disfiguring.

Conditions like melasma or acne can have a profoundly negative impact on self-esteem, quality of life, and job pros-pects, said Dr. Rodriguez.

Melasma is common in Hispanics, particularly in women. "Hispanics commonly attribute melasma to a sick liver, aging, poor nutrition, or lack of sleep," he said, so patients need to understand the role of UV radiation in triggering or exacerbating the condition.

Special care must be taken in treating acne in Hispanic patients because Fitzpatrick skin types IV-VI are susceptible to hyperpigmentation. Hispanic patients are often unaware that they have acne, but they may be concerned about "dark scars or spots," said Dr. Rodriguez. "We must educate them that they have to stop touching or picking their face."

Like other patient populations, Hispanics have misconceptions about the causes of acne, and may attribute outbreaks of acne to certain foods, sex, or ill health. They need to know that the ointments and oils, especially cocoa butter, in popular Hispanic hair and skin treatments can clog pores and worsen acne, he said.

There is a widespread misconception that individuals with dark pigmented skin cannot get skin cancer, so many Hispanics consider sunscreens necessary only for the beach or the pool and do not understand the importance of using sunscreen on a daily basis. Dr. Rodriguez said he recommends that Hispanic patients be reminded to use sunscreen, particularly in regions of the country, such as South Florida, where incidental sun exposure can be intense.

Ideally, dermatologists who treat Hispanic patients should provide Spanish-language materials in the waiting room and offer bilingual take-home instructions. Practices that treat many Hispanic patients should have a bilingual staff, he said.

BUENOS AIRES — The five most common skin disorders of black patients can be effectively managed by understanding that not all skin types are treated the same, reported Dr. Susan C. Taylor at the at the 21st World Congress of Dermatology.

Acne is the most common dermatologic diagnosis seen in black patients. It is unlikely that racial differences affect the pathophysiology of acne, but histopathologically there may be racial differences in sebaceous gland size and activity, said Dr. Taylor, director of the Skin of Color Center at St. Luke's-Roosevelt Hospital, New York.

Inflammation has been seen in the facial comedones of black women, with marked inflammation observed in papular and pustular lesions, she said. "This probably explains why postinflammatory hyperpigmentation is such a huge problem in the black population with acne."

Hyperpigmentation is one of the primary complaints of black patients who seek treatment for acne. "When we address treatment of acne in this population, it behooves us not only to treat the acne early and aggressively but also to treat the postinflammatory hyperpigmentation," said Dr. Taylor. Aggressive therapy must be balanced with the recognition that some topical therapies may be irritating to the skin, leading to further postinflammatory hyperpigmentation. Additional depigmenting therapy may be needed.

Maintenance therapy is advisable in order to prevent formation of new comedones that would lead to acne and postinflammatory hyperpigmentation. Sunscreens and sun protection are essential. "Many people of African descent do not readily embrace the use of sunscreens," she said. "It is very important for us to educate this particular population about the need for sunscreens, particularly as it relates to the stimulation of melanocytes and the production of melanin and further postinflammatory hyperpigmentation."

Acne treatment should include both topical and systemic therapies. "Keep in mind that many of the topical treatments can be irritating to the skin, thereby increasing inflammation," said Dr. Taylor. Standard topical treatments for acne in black patients include benzoyl peroxide, topical antibiotics, and topical retinoids such as tretinoin, adapalene, and tazarotene. In an 18-week, double-blind, vehicle-controlled study, tazarotene 0.1% cream was found to be well tolerated and effective in the treatment of postinflammatory hyperpigmentation in darker-skinned patients with acne vulgaris (Cutis 2006;77:45-50).

Systemic antibiotics include erythromycin, tetracycline, doxycycline, and minocycline; however, minocycline should be used cautiously, as it may induce hyperpigmentation.

Hormonal treatment with oral contraceptives or spironolactone may be effective in some patients.

Postinflammatory hyperpigmentation is the most common pigmentary disorder and can occur at any site of earlier inflammation. The intensity and duration of the hyperpigmentation appears to be linked to the skin hue, affecting those with darker skin color to a greater extent than those with lighter skin color.

Prevention is the most important factor concerning pigmentary disorders. Spot tests always should be performed before initiating cosmetic procedures such as laser therapy, chemical peels, or microdermabrasion in patients. "You never know when a patient is going to have dyschromia or hyperpigmentation," said Dr. Taylor. Remind patients who are susceptible to pigmentary disorders to use sunscreens regularly. For treatment of pigmentary disorders, 4% hydroquinones remain the gold standard, but retinoids can also be effective. Other agents include azelaic acid, kojic acid, and glycolic acid.

Compared with other racial groups, blacks appear to have higher rates of allergic contact dermatitis to thioureas, p-tert-butyl phenol-formaldehyde resin, cobalt chloride, and paraphenylenediamine, a component of dark hair dye. The higher paraphenylenediamine sensitivity may be related to more extensive exposure through the use of dark hair dyes, said Dr. Taylor.

In the treatment of eczema, "attention to skin care cannot be overemphasized," she said. Emollients and bathing rituals can be helpful in alleviating symptoms. Topical corticosteroids and topical immunomodulators are recommended treatments.

Seborrheic dermatitis is a condition that appears to show no racial predilection, but the incidence is increased in patients with HIV or chronic neurologic conditions. It can affect the scalp, face, ears, and chest, causing scaling and pigmentary abnormalities.

Daily shampooing often is recommended for patients with seborrheic dermatitis. "This is not an option for patients of African descent, because of the structural differences of the hair, particularly the dryness, as well as cultural practices," she said, "most patients of African descent only shampoo once a week or once every other week, so you have to tailor your therapy appropriately."

Dr. Taylor has worked as a clinical investigator, speaker, or consultant for Allergan Inc., Beiersdorf AG, Dermik Laboratories, Galderma Laboratories, Medicis Pharmaceutical Corp., Stiefel Laboratories Inc., and Johnson & Johnson.

BUENOS AIRES — The five most common skin disorders of black patients can be effectively managed by understanding that not all skin types are treated the same, reported Dr. Susan C. Taylor at the at the 21st World Congress of Dermatology.

Acne is the most common dermatologic diagnosis seen in black patients. It is unlikely that racial differences affect the pathophysiology of acne, but histopathologically there may be racial differences in sebaceous gland size and activity, said Dr. Taylor, director of the Skin of Color Center at St. Luke's-Roosevelt Hospital, New York.

Inflammation has been seen in the facial comedones of black women, with marked inflammation observed in papular and pustular lesions, she said. "This probably explains why postinflammatory hyperpigmentation is such a huge problem in the black population with acne."

Hyperpigmentation is one of the primary complaints of black patients who seek treatment for acne. "When we address treatment of acne in this population, it behooves us not only to treat the acne early and aggressively but also to treat the postinflammatory hyperpigmentation," said Dr. Taylor. Aggressive therapy must be balanced with the recognition that some topical therapies may be irritating to the skin, leading to further postinflammatory hyperpigmentation. Additional depigmenting therapy may be needed.

Maintenance therapy is advisable in order to prevent formation of new comedones that would lead to acne and postinflammatory hyperpigmentation. Sunscreens and sun protection are essential. "Many people of African descent do not readily embrace the use of sunscreens," she said. "It is very important for us to educate this particular population about the need for sunscreens, particularly as it relates to the stimulation of melanocytes and the production of melanin and further postinflammatory hyperpigmentation."

Acne treatment should include both topical and systemic therapies. "Keep in mind that many of the topical treatments can be irritating to the skin, thereby increasing inflammation," said Dr. Taylor. Standard topical treatments for acne in black patients include benzoyl peroxide, topical antibiotics, and topical retinoids such as tretinoin, adapalene, and tazarotene. In an 18-week, double-blind, vehicle-controlled study, tazarotene 0.1% cream was found to be well tolerated and effective in the treatment of postinflammatory hyperpigmentation in darker-skinned patients with acne vulgaris (Cutis 2006;77:45-50).

Systemic antibiotics include erythromycin, tetracycline, doxycycline, and minocycline; however, minocycline should be used cautiously, as it may induce hyperpigmentation.

Hormonal treatment with oral contraceptives or spironolactone may be effective in some patients.

Postinflammatory hyperpigmentation is the most common pigmentary disorder and can occur at any site of earlier inflammation. The intensity and duration of the hyperpigmentation appears to be linked to the skin hue, affecting those with darker skin color to a greater extent than those with lighter skin color.

Prevention is the most important factor concerning pigmentary disorders. Spot tests always should be performed before initiating cosmetic procedures such as laser therapy, chemical peels, or microdermabrasion in patients. "You never know when a patient is going to have dyschromia or hyperpigmentation," said Dr. Taylor. Remind patients who are susceptible to pigmentary disorders to use sunscreens regularly. For treatment of pigmentary disorders, 4% hydroquinones remain the gold standard, but retinoids can also be effective. Other agents include azelaic acid, kojic acid, and glycolic acid.

Compared with other racial groups, blacks appear to have higher rates of allergic contact dermatitis to thioureas, p-tert-butyl phenol-formaldehyde resin, cobalt chloride, and paraphenylenediamine, a component of dark hair dye. The higher paraphenylenediamine sensitivity may be related to more extensive exposure through the use of dark hair dyes, said Dr. Taylor.

In the treatment of eczema, "attention to skin care cannot be overemphasized," she said. Emollients and bathing rituals can be helpful in alleviating symptoms. Topical corticosteroids and topical immunomodulators are recommended treatments.

Seborrheic dermatitis is a condition that appears to show no racial predilection, but the incidence is increased in patients with HIV or chronic neurologic conditions. It can affect the scalp, face, ears, and chest, causing scaling and pigmentary abnormalities.

Daily shampooing often is recommended for patients with seborrheic dermatitis. "This is not an option for patients of African descent, because of the structural differences of the hair, particularly the dryness, as well as cultural practices," she said, "most patients of African descent only shampoo once a week or once every other week, so you have to tailor your therapy appropriately."

Dr. Taylor has worked as a clinical investigator, speaker, or consultant for Allergan Inc., Beiersdorf AG, Dermik Laboratories, Galderma Laboratories, Medicis Pharmaceutical Corp., Stiefel Laboratories Inc., and Johnson & Johnson.

BUENOS AIRES — The five most common skin disorders of black patients can be effectively managed by understanding that not all skin types are treated the same, reported Dr. Susan C. Taylor at the at the 21st World Congress of Dermatology.

Acne is the most common dermatologic diagnosis seen in black patients. It is unlikely that racial differences affect the pathophysiology of acne, but histopathologically there may be racial differences in sebaceous gland size and activity, said Dr. Taylor, director of the Skin of Color Center at St. Luke's-Roosevelt Hospital, New York.

Inflammation has been seen in the facial comedones of black women, with marked inflammation observed in papular and pustular lesions, she said. "This probably explains why postinflammatory hyperpigmentation is such a huge problem in the black population with acne."

Hyperpigmentation is one of the primary complaints of black patients who seek treatment for acne. "When we address treatment of acne in this population, it behooves us not only to treat the acne early and aggressively but also to treat the postinflammatory hyperpigmentation," said Dr. Taylor. Aggressive therapy must be balanced with the recognition that some topical therapies may be irritating to the skin, leading to further postinflammatory hyperpigmentation. Additional depigmenting therapy may be needed.

Maintenance therapy is advisable in order to prevent formation of new comedones that would lead to acne and postinflammatory hyperpigmentation. Sunscreens and sun protection are essential. "Many people of African descent do not readily embrace the use of sunscreens," she said. "It is very important for us to educate this particular population about the need for sunscreens, particularly as it relates to the stimulation of melanocytes and the production of melanin and further postinflammatory hyperpigmentation."

Acne treatment should include both topical and systemic therapies. "Keep in mind that many of the topical treatments can be irritating to the skin, thereby increasing inflammation," said Dr. Taylor. Standard topical treatments for acne in black patients include benzoyl peroxide, topical antibiotics, and topical retinoids such as tretinoin, adapalene, and tazarotene. In an 18-week, double-blind, vehicle-controlled study, tazarotene 0.1% cream was found to be well tolerated and effective in the treatment of postinflammatory hyperpigmentation in darker-skinned patients with acne vulgaris (Cutis 2006;77:45-50).

Systemic antibiotics include erythromycin, tetracycline, doxycycline, and minocycline; however, minocycline should be used cautiously, as it may induce hyperpigmentation.

Hormonal treatment with oral contraceptives or spironolactone may be effective in some patients.

Postinflammatory hyperpigmentation is the most common pigmentary disorder and can occur at any site of earlier inflammation. The intensity and duration of the hyperpigmentation appears to be linked to the skin hue, affecting those with darker skin color to a greater extent than those with lighter skin color.

Prevention is the most important factor concerning pigmentary disorders. Spot tests always should be performed before initiating cosmetic procedures such as laser therapy, chemical peels, or microdermabrasion in patients. "You never know when a patient is going to have dyschromia or hyperpigmentation," said Dr. Taylor. Remind patients who are susceptible to pigmentary disorders to use sunscreens regularly. For treatment of pigmentary disorders, 4% hydroquinones remain the gold standard, but retinoids can also be effective. Other agents include azelaic acid, kojic acid, and glycolic acid.

Compared with other racial groups, blacks appear to have higher rates of allergic contact dermatitis to thioureas, p-tert-butyl phenol-formaldehyde resin, cobalt chloride, and paraphenylenediamine, a component of dark hair dye. The higher paraphenylenediamine sensitivity may be related to more extensive exposure through the use of dark hair dyes, said Dr. Taylor.

In the treatment of eczema, "attention to skin care cannot be overemphasized," she said. Emollients and bathing rituals can be helpful in alleviating symptoms. Topical corticosteroids and topical immunomodulators are recommended treatments.

Seborrheic dermatitis is a condition that appears to show no racial predilection, but the incidence is increased in patients with HIV or chronic neurologic conditions. It can affect the scalp, face, ears, and chest, causing scaling and pigmentary abnormalities.

Daily shampooing often is recommended for patients with seborrheic dermatitis. "This is not an option for patients of African descent, because of the structural differences of the hair, particularly the dryness, as well as cultural practices," she said, "most patients of African descent only shampoo once a week or once every other week, so you have to tailor your therapy appropriately."

Dr. Taylor has worked as a clinical investigator, speaker, or consultant for Allergan Inc., Beiersdorf AG, Dermik Laboratories, Galderma Laboratories, Medicis Pharmaceutical Corp., Stiefel Laboratories Inc., and Johnson & Johnson.

BUENOS AIRES — Diagnosing Henoch-Schönlein purpura requires a small-vessel biopsy to confirm the presence of IgA, Dr. Thomas G. Cropley said at the 21st World Congress of Dermatology.

IgA deposits in vessel walls, along with prominent extracutaneous manifestations, are the hallmarks of Henoch-Schönlein purpura (HSP), a specific type of small-size vessel vasculitis that is the most common vasculitis syndrome in children, often occurring after a respiratory tract infection.

In recent years, three different sets of classification criteria have been proposed, the oldest of which does not list IgA deposition in its diagnostic criteria. In 1990, the American College of Rheumatology published its classification of Henoch-Schönlein purpura (Arthritis Rheum. 1990;33: 1114–21), requiring four diagnostic criteria:

▸ Palpable purpura, defined as slightly raised “palpable” hemorrhagic skin lesions not related to thrombocytopenia;

▸ Age less than 20 years at disease onset;

▸ Bowel angina, or diffuse abdominal pain, which might include bloody diarrhea;

▸ Presence of granulocytes in vessel walls.

“There is no mention of immunofluorescence or IgA here,” said Dr. Cropley. The ACR definition is based only on histo- pathology and clinical symptoms. Dermatologists were not involved in developing the classification system, which has been criticized for the “lack of dermatological insight,” said Dr. Cropley, professor of medicine in the division of dermatology at the University of Massachusetts, Worcester.

A group of physicians that included rheumatologists, nephrologists, and pulmonologists (but not dermatologists) convened in Chapel Hill, N.C., in 1994 and developed consensus guidelines for the diagnosis of various forms of vasculitis, including HSP (Arthritis Rheum. 1994;37:187–92). “[This] definition of Henoch- Schönlein purpura requires the presence of vasculitis with IgA-dominant immune deposits affecting small vessels, which they defined as capillaries, venules, or arterioles,” said Dr. Cropley. The definition noted that the vasculitis typically involves skin, gut, and glomeruli and that the condition is associated with arthralgias or arthritis. “IgA is part of the definition, but there are still many other areas of 'looseness' in this definition.”

In 2006, the European League Against Rheumatism and the Paediatric Rheumatology Society published Classification Criteria for Henoch-Schönlein purpura (Ann. Rheum. Dis. 2006;65:936–41). In their definition, the presence of palpable purpura is a mandatory criterion, and at least one of the following four features must be present: diffuse abdominal pain; biopsy-proved predominant IgA deposition; acute arthritis in any joint or arthralgia; and renal involvement (hematuria and/or proteinuria).

The epidemiology of HSP is well described. In the United States, the incidence is about 10 cases per 10,000. About 75% of cases begin in childhood, with an equal prevalence in males and in females. The disease is often preceded by a respiratory tract infection, but no typical or unique pathogen has been associated with it, said Dr. Cropley.

Adult cases are less likely to be associated with an antecedent infection, and the prevalence is higher in men than in women.

Differential diagnosis of Henoch-Schönlein purpura includes other forms of small-size vessel vasculitis causing palpable purpura, such as Wegener's granulomatosis, IgG leukocytoclastic vasculitis, and microscopic polyangiitis. Other IgA-associated vasculitides should also be considered, including IgA rheumatoid factor-associated small-vessel vasculitis and acute hemorrhagic edema of infancy.

The question of whether or not the presence of IgA predicts an increased likelihood of renal involvement is unanswered. An epidemiologic study of HSP showed renal involvement occurred in one-third of the children with the disease (Kidney Int. 1998;53:1755–9). Significant independent risk factors for chronic renal disease in these patients were severe abdominal symptoms, prolonged purpura, and decreased factor XIII activity. But the prognostic significance of IgA status could not be evaluated in the study, because the researchers used the 1990 ACR diagnostic criteria of Henoch-Schönlein purpura.

IgA deposition is a defining criterion of Henoch-Schönlein purpura in the two most recent diagnostic guidelines. Patients with the condition may have a poorer prognosis concerning renal involvement than patients with other forms of small-vessel vasculitis. As such, Dr. Cropley recommended a biopsy for immunofluorescence and histopathology, if possible, in patients who seem to have Henoch- Schönlein purpura. Serum IgA levels have been shown to correlate with the risk of IgA nephropathy in adults with Henoch-Schönlein purpura; thus, monitoring serum IgA level over time may help identify patients at particular risk of chronic renal disease. He reports no conflicts of interest.

Even in the presence of palpable lesions, vessel biopsy is required to diagnose Henoch-Schönlein purpura. Courtesy Dr. Lauren Alberta-Wszolek

BUENOS AIRES — Diagnosing Henoch-Schönlein purpura requires a small-vessel biopsy to confirm the presence of IgA, Dr. Thomas G. Cropley said at the 21st World Congress of Dermatology.

IgA deposits in vessel walls, along with prominent extracutaneous manifestations, are the hallmarks of Henoch-Schönlein purpura (HSP), a specific type of small-size vessel vasculitis that is the most common vasculitis syndrome in children, often occurring after a respiratory tract infection.

In recent years, three different sets of classification criteria have been proposed, the oldest of which does not list IgA deposition in its diagnostic criteria. In 1990, the American College of Rheumatology published its classification of Henoch-Schönlein purpura (Arthritis Rheum. 1990;33: 1114–21), requiring four diagnostic criteria:

▸ Palpable purpura, defined as slightly raised “palpable” hemorrhagic skin lesions not related to thrombocytopenia;

▸ Age less than 20 years at disease onset;

▸ Bowel angina, or diffuse abdominal pain, which might include bloody diarrhea;

▸ Presence of granulocytes in vessel walls.

“There is no mention of immunofluorescence or IgA here,” said Dr. Cropley. The ACR definition is based only on histo- pathology and clinical symptoms. Dermatologists were not involved in developing the classification system, which has been criticized for the “lack of dermatological insight,” said Dr. Cropley, professor of medicine in the division of dermatology at the University of Massachusetts, Worcester.

A group of physicians that included rheumatologists, nephrologists, and pulmonologists (but not dermatologists) convened in Chapel Hill, N.C., in 1994 and developed consensus guidelines for the diagnosis of various forms of vasculitis, including HSP (Arthritis Rheum. 1994;37:187–92). “[This] definition of Henoch- Schönlein purpura requires the presence of vasculitis with IgA-dominant immune deposits affecting small vessels, which they defined as capillaries, venules, or arterioles,” said Dr. Cropley. The definition noted that the vasculitis typically involves skin, gut, and glomeruli and that the condition is associated with arthralgias or arthritis. “IgA is part of the definition, but there are still many other areas of 'looseness' in this definition.”

In 2006, the European League Against Rheumatism and the Paediatric Rheumatology Society published Classification Criteria for Henoch-Schönlein purpura (Ann. Rheum. Dis. 2006;65:936–41). In their definition, the presence of palpable purpura is a mandatory criterion, and at least one of the following four features must be present: diffuse abdominal pain; biopsy-proved predominant IgA deposition; acute arthritis in any joint or arthralgia; and renal involvement (hematuria and/or proteinuria).

The epidemiology of HSP is well described. In the United States, the incidence is about 10 cases per 10,000. About 75% of cases begin in childhood, with an equal prevalence in males and in females. The disease is often preceded by a respiratory tract infection, but no typical or unique pathogen has been associated with it, said Dr. Cropley.

Adult cases are less likely to be associated with an antecedent infection, and the prevalence is higher in men than in women.

Differential diagnosis of Henoch-Schönlein purpura includes other forms of small-size vessel vasculitis causing palpable purpura, such as Wegener's granulomatosis, IgG leukocytoclastic vasculitis, and microscopic polyangiitis. Other IgA-associated vasculitides should also be considered, including IgA rheumatoid factor-associated small-vessel vasculitis and acute hemorrhagic edema of infancy.

The question of whether or not the presence of IgA predicts an increased likelihood of renal involvement is unanswered. An epidemiologic study of HSP showed renal involvement occurred in one-third of the children with the disease (Kidney Int. 1998;53:1755–9). Significant independent risk factors for chronic renal disease in these patients were severe abdominal symptoms, prolonged purpura, and decreased factor XIII activity. But the prognostic significance of IgA status could not be evaluated in the study, because the researchers used the 1990 ACR diagnostic criteria of Henoch-Schönlein purpura.

IgA deposition is a defining criterion of Henoch-Schönlein purpura in the two most recent diagnostic guidelines. Patients with the condition may have a poorer prognosis concerning renal involvement than patients with other forms of small-vessel vasculitis. As such, Dr. Cropley recommended a biopsy for immunofluorescence and histopathology, if possible, in patients who seem to have Henoch- Schönlein purpura. Serum IgA levels have been shown to correlate with the risk of IgA nephropathy in adults with Henoch-Schönlein purpura; thus, monitoring serum IgA level over time may help identify patients at particular risk of chronic renal disease. He reports no conflicts of interest.

Even in the presence of palpable lesions, vessel biopsy is required to diagnose Henoch-Schönlein purpura. Courtesy Dr. Lauren Alberta-Wszolek

BUENOS AIRES — Diagnosing Henoch-Schönlein purpura requires a small-vessel biopsy to confirm the presence of IgA, Dr. Thomas G. Cropley said at the 21st World Congress of Dermatology.

IgA deposits in vessel walls, along with prominent extracutaneous manifestations, are the hallmarks of Henoch-Schönlein purpura (HSP), a specific type of small-size vessel vasculitis that is the most common vasculitis syndrome in children, often occurring after a respiratory tract infection.

In recent years, three different sets of classification criteria have been proposed, the oldest of which does not list IgA deposition in its diagnostic criteria. In 1990, the American College of Rheumatology published its classification of Henoch-Schönlein purpura (Arthritis Rheum. 1990;33: 1114–21), requiring four diagnostic criteria:

▸ Palpable purpura, defined as slightly raised “palpable” hemorrhagic skin lesions not related to thrombocytopenia;

▸ Age less than 20 years at disease onset;

▸ Bowel angina, or diffuse abdominal pain, which might include bloody diarrhea;

▸ Presence of granulocytes in vessel walls.

“There is no mention of immunofluorescence or IgA here,” said Dr. Cropley. The ACR definition is based only on histo- pathology and clinical symptoms. Dermatologists were not involved in developing the classification system, which has been criticized for the “lack of dermatological insight,” said Dr. Cropley, professor of medicine in the division of dermatology at the University of Massachusetts, Worcester.

A group of physicians that included rheumatologists, nephrologists, and pulmonologists (but not dermatologists) convened in Chapel Hill, N.C., in 1994 and developed consensus guidelines for the diagnosis of various forms of vasculitis, including HSP (Arthritis Rheum. 1994;37:187–92). “[This] definition of Henoch- Schönlein purpura requires the presence of vasculitis with IgA-dominant immune deposits affecting small vessels, which they defined as capillaries, venules, or arterioles,” said Dr. Cropley. The definition noted that the vasculitis typically involves skin, gut, and glomeruli and that the condition is associated with arthralgias or arthritis. “IgA is part of the definition, but there are still many other areas of 'looseness' in this definition.”

In 2006, the European League Against Rheumatism and the Paediatric Rheumatology Society published Classification Criteria for Henoch-Schönlein purpura (Ann. Rheum. Dis. 2006;65:936–41). In their definition, the presence of palpable purpura is a mandatory criterion, and at least one of the following four features must be present: diffuse abdominal pain; biopsy-proved predominant IgA deposition; acute arthritis in any joint or arthralgia; and renal involvement (hematuria and/or proteinuria).

The epidemiology of HSP is well described. In the United States, the incidence is about 10 cases per 10,000. About 75% of cases begin in childhood, with an equal prevalence in males and in females. The disease is often preceded by a respiratory tract infection, but no typical or unique pathogen has been associated with it, said Dr. Cropley.

Adult cases are less likely to be associated with an antecedent infection, and the prevalence is higher in men than in women.

Differential diagnosis of Henoch-Schönlein purpura includes other forms of small-size vessel vasculitis causing palpable purpura, such as Wegener's granulomatosis, IgG leukocytoclastic vasculitis, and microscopic polyangiitis. Other IgA-associated vasculitides should also be considered, including IgA rheumatoid factor-associated small-vessel vasculitis and acute hemorrhagic edema of infancy.

The question of whether or not the presence of IgA predicts an increased likelihood of renal involvement is unanswered. An epidemiologic study of HSP showed renal involvement occurred in one-third of the children with the disease (Kidney Int. 1998;53:1755–9). Significant independent risk factors for chronic renal disease in these patients were severe abdominal symptoms, prolonged purpura, and decreased factor XIII activity. But the prognostic significance of IgA status could not be evaluated in the study, because the researchers used the 1990 ACR diagnostic criteria of Henoch-Schönlein purpura.

IgA deposition is a defining criterion of Henoch-Schönlein purpura in the two most recent diagnostic guidelines. Patients with the condition may have a poorer prognosis concerning renal involvement than patients with other forms of small-vessel vasculitis. As such, Dr. Cropley recommended a biopsy for immunofluorescence and histopathology, if possible, in patients who seem to have Henoch- Schönlein purpura. Serum IgA levels have been shown to correlate with the risk of IgA nephropathy in adults with Henoch-Schönlein purpura; thus, monitoring serum IgA level over time may help identify patients at particular risk of chronic renal disease. He reports no conflicts of interest.

Even in the presence of palpable lesions, vessel biopsy is required to diagnose Henoch-Schönlein purpura. Courtesy Dr. Lauren Alberta-Wszolek

The diagnosis of Henoch-Schönlein purpura requires a small-vessel biopsy to confirm the presence of IgA, Dr. Thomas G. Cropley said at the 21st World Congress of Dermatology in Buenos Aires.

IgA deposits in vessel walls along with prominent extracutaneous manifestations are the hallmarks of Henoch-Schönlein purpura, a specific type of small-size vessel vasculitis that is the most common vasculitis syndrome in children, often occurring after a respiratory tract infection.

In recent years three different sets of classification criteria have been proposed, the oldest of which does not list IgA deposition among its diagnostic criteria. In 1990, the American College of Rheumatology published its Classification of Henoch-Schönlein purpura (Arthritis Rheum. 1990;33:1114–21), which requires four diagnostic criteria:

▸ Palpable purpura, defined as raised “palpable” hemorrhagic skin lesions not related to thrombocytopenia;

▸ Age less than 20 years at disease onset;

▸ Bowel angina, or diffuse abdominal pain, which might include bloody diarrhea;

▸ Presence of granulocytes in vessel walls.

“Notice that there is no mention of immunofluorescence or IgA here,” said Dr. Cropley. The ACR definition is based only on histopathology and clinical symptoms. Dermatologists were not involved in developing the classification system, which has since been criticized for the “rather obvious lack of dermatological insight,” said Dr. Cropley, professor of medicine in the division of dermatology at the University of Massachusetts, Worcester.

A group of rheumatologists, nephrologists, and pulmonologists convened in Chapel Hill, N.C., in 1994 and developed consensus guidelines for the diagnosis of various forms of vasculitis, including Henoch-Schönlein purpura (Arthritis Rheum. 1994;37:187–92). “The Chapel Hill definition of Henoch-Schönlein purpura requires the presence of vasculitis with IgA-dominant immune deposits affecting small vessels, which they defined as capillaries, venules, or arterioles,” said Dr. Cropley. The definition noted the vasculitis typically involves skin, gut, and glomeruli and is associated with arthralgias or arthritis. “IgA is part of the definition, but there are still many other areas of 'looseness' in this definition.”

In 2006 the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology Society published Classification Criteria for Henoch-Schönlein purpura (Ann. Rheum. Dis. 2006;65:936–41). In their version, palpable purpura is a mandatory criterion and at least one of the following must be present: diffuse abdominal pain; biopsy-proved predominant IgA deposition; acute arthritis in any joint or arthralgia; and renal involvement (hematuria and/or proteinuria).

The epidemiology of Henoch-Schönlein purpura is well described. In the United States, the incidence is about 10 cases per 10,000. The majority of cases (about 75%) begin in childhood, with an equal prevalence in males and females. The disease is often preceded by a respiratory tract infection, but no typical or unique pathogen has been associated with the disease, said Dr. Cropley. Prevalence is highest in the autumn and winter, when respiratory tract infections are more common.

Adult cases are less likely to be associated with an antecedent infection. The prevalence of adult-onset is higher in men than in women. “There is anecdotal evidence suggesting that there may be an increased association with malignancy in adult cases,” said Dr. Cropley.

Differential diagnosis of Henoch-Schönlein purpura includes other forms of small-size vessel vasculitis causing palpable purpura, such as IgG leukocytoclastic vasculitis, Wegener's granulomatosis, and microscopic polyangiitis. Other IgA-associated vasculitides should also be considered, including IgA rheumatoid factor-associated small-vessel vasculitis and acute hemorrhagic edema of infancy.

Whether the presence of IgA predicts an increased risk of renal involvement is unknown. An extensive epidemiologic study of Henoch-Schönlein purpura showed renal involvement in one-third of children (Kidney Int. 1998;53:1755–9). Significant independent risk factors for chronic renal disease were severe abdominal symptoms, prolonged purpura, and decreased factor XIII activity. The prognostic significance of IgA status was not evaluated, because the study used the 1990 ACR diagnostic criteria.

IgA deposition is a defining criterion of Henoch-Schönlein purpura in the two most recent diagnostic guidelines. Henoch-Schönlein purpura patients may have a poorer renal prognosis than patients with other forms of small-vessel vasculitis. For these reasons, Dr. Cropley recommends a biopsy for immunofluorescence and histopathology, if possible, in patients who appear to have Henoch-Schönlein purpura. Serum IgA levels have been correlated with the risk of IgA nephropathy in adults with Henoch-Schönlein purpura; thus, monitoring serum IgA level over time may help identify patients at risk of chronic renal disease.

Dr. Cropley reported no conflicts of interest.

Even in the presence of palpable lesions, vessel biopsy is required to diagnose Henoch-Schönlein purpura. COURTESY DR. LAUREN ALBERTA-WSZOLEK

The diagnosis of Henoch-Schönlein purpura requires a small-vessel biopsy to confirm the presence of IgA, Dr. Thomas G. Cropley said at the 21st World Congress of Dermatology in Buenos Aires.

IgA deposits in vessel walls along with prominent extracutaneous manifestations are the hallmarks of Henoch-Schönlein purpura, a specific type of small-size vessel vasculitis that is the most common vasculitis syndrome in children, often occurring after a respiratory tract infection.

In recent years three different sets of classification criteria have been proposed, the oldest of which does not list IgA deposition among its diagnostic criteria. In 1990, the American College of Rheumatology published its Classification of Henoch-Schönlein purpura (Arthritis Rheum. 1990;33:1114–21), which requires four diagnostic criteria:

▸ Palpable purpura, defined as raised “palpable” hemorrhagic skin lesions not related to thrombocytopenia;

▸ Age less than 20 years at disease onset;

▸ Bowel angina, or diffuse abdominal pain, which might include bloody diarrhea;

▸ Presence of granulocytes in vessel walls.

“Notice that there is no mention of immunofluorescence or IgA here,” said Dr. Cropley. The ACR definition is based only on histopathology and clinical symptoms. Dermatologists were not involved in developing the classification system, which has since been criticized for the “rather obvious lack of dermatological insight,” said Dr. Cropley, professor of medicine in the division of dermatology at the University of Massachusetts, Worcester.

A group of rheumatologists, nephrologists, and pulmonologists convened in Chapel Hill, N.C., in 1994 and developed consensus guidelines for the diagnosis of various forms of vasculitis, including Henoch-Schönlein purpura (Arthritis Rheum. 1994;37:187–92). “The Chapel Hill definition of Henoch-Schönlein purpura requires the presence of vasculitis with IgA-dominant immune deposits affecting small vessels, which they defined as capillaries, venules, or arterioles,” said Dr. Cropley. The definition noted the vasculitis typically involves skin, gut, and glomeruli and is associated with arthralgias or arthritis. “IgA is part of the definition, but there are still many other areas of 'looseness' in this definition.”

In 2006 the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology Society published Classification Criteria for Henoch-Schönlein purpura (Ann. Rheum. Dis. 2006;65:936–41). In their version, palpable purpura is a mandatory criterion and at least one of the following must be present: diffuse abdominal pain; biopsy-proved predominant IgA deposition; acute arthritis in any joint or arthralgia; and renal involvement (hematuria and/or proteinuria).

The epidemiology of Henoch-Schönlein purpura is well described. In the United States, the incidence is about 10 cases per 10,000. The majority of cases (about 75%) begin in childhood, with an equal prevalence in males and females. The disease is often preceded by a respiratory tract infection, but no typical or unique pathogen has been associated with the disease, said Dr. Cropley. Prevalence is highest in the autumn and winter, when respiratory tract infections are more common.

Adult cases are less likely to be associated with an antecedent infection. The prevalence of adult-onset is higher in men than in women. “There is anecdotal evidence suggesting that there may be an increased association with malignancy in adult cases,” said Dr. Cropley.

Differential diagnosis of Henoch-Schönlein purpura includes other forms of small-size vessel vasculitis causing palpable purpura, such as IgG leukocytoclastic vasculitis, Wegener's granulomatosis, and microscopic polyangiitis. Other IgA-associated vasculitides should also be considered, including IgA rheumatoid factor-associated small-vessel vasculitis and acute hemorrhagic edema of infancy.

Whether the presence of IgA predicts an increased risk of renal involvement is unknown. An extensive epidemiologic study of Henoch-Schönlein purpura showed renal involvement in one-third of children (Kidney Int. 1998;53:1755–9). Significant independent risk factors for chronic renal disease were severe abdominal symptoms, prolonged purpura, and decreased factor XIII activity. The prognostic significance of IgA status was not evaluated, because the study used the 1990 ACR diagnostic criteria.

IgA deposition is a defining criterion of Henoch-Schönlein purpura in the two most recent diagnostic guidelines. Henoch-Schönlein purpura patients may have a poorer renal prognosis than patients with other forms of small-vessel vasculitis. For these reasons, Dr. Cropley recommends a biopsy for immunofluorescence and histopathology, if possible, in patients who appear to have Henoch-Schönlein purpura. Serum IgA levels have been correlated with the risk of IgA nephropathy in adults with Henoch-Schönlein purpura; thus, monitoring serum IgA level over time may help identify patients at risk of chronic renal disease.

Dr. Cropley reported no conflicts of interest.

Even in the presence of palpable lesions, vessel biopsy is required to diagnose Henoch-Schönlein purpura. COURTESY DR. LAUREN ALBERTA-WSZOLEK

The diagnosis of Henoch-Schönlein purpura requires a small-vessel biopsy to confirm the presence of IgA, Dr. Thomas G. Cropley said at the 21st World Congress of Dermatology in Buenos Aires.

IgA deposits in vessel walls along with prominent extracutaneous manifestations are the hallmarks of Henoch-Schönlein purpura, a specific type of small-size vessel vasculitis that is the most common vasculitis syndrome in children, often occurring after a respiratory tract infection.

In recent years three different sets of classification criteria have been proposed, the oldest of which does not list IgA deposition among its diagnostic criteria. In 1990, the American College of Rheumatology published its Classification of Henoch-Schönlein purpura (Arthritis Rheum. 1990;33:1114–21), which requires four diagnostic criteria:

▸ Palpable purpura, defined as raised “palpable” hemorrhagic skin lesions not related to thrombocytopenia;

▸ Age less than 20 years at disease onset;

▸ Bowel angina, or diffuse abdominal pain, which might include bloody diarrhea;

▸ Presence of granulocytes in vessel walls.

“Notice that there is no mention of immunofluorescence or IgA here,” said Dr. Cropley. The ACR definition is based only on histopathology and clinical symptoms. Dermatologists were not involved in developing the classification system, which has since been criticized for the “rather obvious lack of dermatological insight,” said Dr. Cropley, professor of medicine in the division of dermatology at the University of Massachusetts, Worcester.

A group of rheumatologists, nephrologists, and pulmonologists convened in Chapel Hill, N.C., in 1994 and developed consensus guidelines for the diagnosis of various forms of vasculitis, including Henoch-Schönlein purpura (Arthritis Rheum. 1994;37:187–92). “The Chapel Hill definition of Henoch-Schönlein purpura requires the presence of vasculitis with IgA-dominant immune deposits affecting small vessels, which they defined as capillaries, venules, or arterioles,” said Dr. Cropley. The definition noted the vasculitis typically involves skin, gut, and glomeruli and is associated with arthralgias or arthritis. “IgA is part of the definition, but there are still many other areas of 'looseness' in this definition.”

In 2006 the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology Society published Classification Criteria for Henoch-Schönlein purpura (Ann. Rheum. Dis. 2006;65:936–41). In their version, palpable purpura is a mandatory criterion and at least one of the following must be present: diffuse abdominal pain; biopsy-proved predominant IgA deposition; acute arthritis in any joint or arthralgia; and renal involvement (hematuria and/or proteinuria).

The epidemiology of Henoch-Schönlein purpura is well described. In the United States, the incidence is about 10 cases per 10,000. The majority of cases (about 75%) begin in childhood, with an equal prevalence in males and females. The disease is often preceded by a respiratory tract infection, but no typical or unique pathogen has been associated with the disease, said Dr. Cropley. Prevalence is highest in the autumn and winter, when respiratory tract infections are more common.

Adult cases are less likely to be associated with an antecedent infection. The prevalence of adult-onset is higher in men than in women. “There is anecdotal evidence suggesting that there may be an increased association with malignancy in adult cases,” said Dr. Cropley.

Differential diagnosis of Henoch-Schönlein purpura includes other forms of small-size vessel vasculitis causing palpable purpura, such as IgG leukocytoclastic vasculitis, Wegener's granulomatosis, and microscopic polyangiitis. Other IgA-associated vasculitides should also be considered, including IgA rheumatoid factor-associated small-vessel vasculitis and acute hemorrhagic edema of infancy.

Whether the presence of IgA predicts an increased risk of renal involvement is unknown. An extensive epidemiologic study of Henoch-Schönlein purpura showed renal involvement in one-third of children (Kidney Int. 1998;53:1755–9). Significant independent risk factors for chronic renal disease were severe abdominal symptoms, prolonged purpura, and decreased factor XIII activity. The prognostic significance of IgA status was not evaluated, because the study used the 1990 ACR diagnostic criteria.

IgA deposition is a defining criterion of Henoch-Schönlein purpura in the two most recent diagnostic guidelines. Henoch-Schönlein purpura patients may have a poorer renal prognosis than patients with other forms of small-vessel vasculitis. For these reasons, Dr. Cropley recommends a biopsy for immunofluorescence and histopathology, if possible, in patients who appear to have Henoch-Schönlein purpura. Serum IgA levels have been correlated with the risk of IgA nephropathy in adults with Henoch-Schönlein purpura; thus, monitoring serum IgA level over time may help identify patients at risk of chronic renal disease.

Dr. Cropley reported no conflicts of interest.

Even in the presence of palpable lesions, vessel biopsy is required to diagnose Henoch-Schönlein purpura. COURTESY DR. LAUREN ALBERTA-WSZOLEK

Metformin and second-generation sulfonylureas appear to be as safe and effective as the newer, more expensive oral diabetes drugs in the treatment of type 2 diabetes in adults, according to Dr. Shari Bolen of Johns Hopkins University, Baltimore, and colleagues.

The researchers analyzed safety and efficacy data from 216 controlled clinical trials and cohort studies of oral diabetes agents, along with two systematic reviews. The studies and reviews were selected from published reports in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and from unpublished reports from industry and the Food and Drug Administration.

“Each oral diabetes agent is associated with adverse events that counterbalance its benefits,” wrote Dr. Bolen and colleagues. “Overall, metformin seemed to have the best profile of benefit to risk.” The American Diabetes Association favors metformin as initial pharmacotherapy for type 2 diabetes, although the choice of therapy often depends upon patient comorbidities.

Metformin and second-generation sulfonylureas were generally as effective as newer agents in improving intermediate outcomes. As monotherapy, all oral diabetes agents had similar effects on glycemic control, with an absolute reduction in hemoglobin A_1c levels of about 1 percentage point. The effects on glycemic control were additive when oral diabetes agents were used in combination therapy. The various agents did not differ significantly in their effect on systolic or diastolic blood pressure.

Only thiazolidinediones improved HDL-cholesterol levels, with a relative mean increase of 0.08–0.13 mmol/L, compared with treatment with other agents. However, thiazolidinediones also increased LDL cholesterol levels by a relative mean increase of 0.26 mmol/L. Metformin improved LDL cholesterol levels by a mean decrease of 0.26 mmol/L. Other oral diabetes agents did not appear to affect LDL cholesterol levels.

Metformin treatment was not associated with weight gain, compared with other agents or placebo. Acarbose treatment also did not lead to weight gain, compared with placebo. Weight gains ranging from 1 to 5 kg were seen with most other oral diabetes medications: thiazolidinediones, repaglinide, and second-generation sulfonylureas. They found no evidence of increased risk of lactic acidosis with metformin, compared with other oral diabetes agents. Hypoglycemic episodes occurred more frequently with second-generation sulfonylureas and repaglinide than with metformin or thiazolidinediones, although there was wide variation in the risk levels reported from the different clinical trials. Gastrointestinal symptoms were most frequent with metformin treatment, ranging from 2% to 63%, a higher rate than most other agents.

In short-term randomized trials, greater risk of congestive heart failure was seen with thiazolidinediones, compared with second-generation sulfonylureas or metformin. The absolute risk of congestive heart failure ranged from 0.8% to 3.6% for thiazolidinediones and from 0% to 2.6% for other oral diabetes agents. In placebo-controlled trials and cohort studies neither second-generation sulfonylureas nor metformin showed increased risk of congestive heart failure.

Because few studies have analyzed major clinical outcomes, data were insufficient for a thorough comparison of the effects of various oral diabetes agents on cardiovascular morbidity and mortality, microvascular outcomes, neuropathy, or death from any cause. “Large, long-term comparative studies on major clinical end points, such as myocardial infarction, chronic kidney disease, and cardiovascular mortality, are needed to determine definitively the comparative effects of the oral diabetes agents, especially in light of recent controversy regarding rosiglitazone,” they wrote.

In an interview, Dr. Zachary Bloomgarden of Mount Sinai School of Medicine in New York, agreed with the researchers' conclusion that the various agents have similar glucose-lowering events but challenged their conclusion that metformin is not associated with increased risk of lactic acidosis, citing toxicology evidence from numerous animal studies. The review “appears not to address much of the relevant information on this immense topic.”

Dr. Bloomgarden has served as a consultant for Merck and on speaker panels for Takeda, GlaxoSmithKline, Novo Nordisk, Eli Lilly, Amylin, Merck, and Novartis.

Metformin and second-generation sulfonylureas appear to be as safe and effective as the newer, more expensive oral diabetes drugs in the treatment of type 2 diabetes in adults, according to Dr. Shari Bolen of Johns Hopkins University, Baltimore, and colleagues.

The researchers analyzed safety and efficacy data from 216 controlled clinical trials and cohort studies of oral diabetes agents, along with two systematic reviews. The studies and reviews were selected from published reports in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and from unpublished reports from industry and the Food and Drug Administration.

“Each oral diabetes agent is associated with adverse events that counterbalance its benefits,” wrote Dr. Bolen and colleagues. “Overall, metformin seemed to have the best profile of benefit to risk.” The American Diabetes Association favors metformin as initial pharmacotherapy for type 2 diabetes, although the choice of therapy often depends upon patient comorbidities.

Metformin and second-generation sulfonylureas were generally as effective as newer agents in improving intermediate outcomes. As monotherapy, all oral diabetes agents had similar effects on glycemic control, with an absolute reduction in hemoglobin A_1c levels of about 1 percentage point. The effects on glycemic control were additive when oral diabetes agents were used in combination therapy. The various agents did not differ significantly in their effect on systolic or diastolic blood pressure.

Only thiazolidinediones improved HDL-cholesterol levels, with a relative mean increase of 0.08–0.13 mmol/L, compared with treatment with other agents. However, thiazolidinediones also increased LDL cholesterol levels by a relative mean increase of 0.26 mmol/L. Metformin improved LDL cholesterol levels by a mean decrease of 0.26 mmol/L. Other oral diabetes agents did not appear to affect LDL cholesterol levels.

Metformin treatment was not associated with weight gain, compared with other agents or placebo. Acarbose treatment also did not lead to weight gain, compared with placebo. Weight gains ranging from 1 to 5 kg were seen with most other oral diabetes medications: thiazolidinediones, repaglinide, and second-generation sulfonylureas. They found no evidence of increased risk of lactic acidosis with metformin, compared with other oral diabetes agents. Hypoglycemic episodes occurred more frequently with second-generation sulfonylureas and repaglinide than with metformin or thiazolidinediones, although there was wide variation in the risk levels reported from the different clinical trials. Gastrointestinal symptoms were most frequent with metformin treatment, ranging from 2% to 63%, a higher rate than most other agents.

In short-term randomized trials, greater risk of congestive heart failure was seen with thiazolidinediones, compared with second-generation sulfonylureas or metformin. The absolute risk of congestive heart failure ranged from 0.8% to 3.6% for thiazolidinediones and from 0% to 2.6% for other oral diabetes agents. In placebo-controlled trials and cohort studies neither second-generation sulfonylureas nor metformin showed increased risk of congestive heart failure.

Because few studies have analyzed major clinical outcomes, data were insufficient for a thorough comparison of the effects of various oral diabetes agents on cardiovascular morbidity and mortality, microvascular outcomes, neuropathy, or death from any cause. “Large, long-term comparative studies on major clinical end points, such as myocardial infarction, chronic kidney disease, and cardiovascular mortality, are needed to determine definitively the comparative effects of the oral diabetes agents, especially in light of recent controversy regarding rosiglitazone,” they wrote.

In an interview, Dr. Zachary Bloomgarden of Mount Sinai School of Medicine in New York, agreed with the researchers' conclusion that the various agents have similar glucose-lowering events but challenged their conclusion that metformin is not associated with increased risk of lactic acidosis, citing toxicology evidence from numerous animal studies. The review “appears not to address much of the relevant information on this immense topic.”

Dr. Bloomgarden has served as a consultant for Merck and on speaker panels for Takeda, GlaxoSmithKline, Novo Nordisk, Eli Lilly, Amylin, Merck, and Novartis.

Metformin and second-generation sulfonylureas appear to be as safe and effective as the newer, more expensive oral diabetes drugs in the treatment of type 2 diabetes in adults, according to Dr. Shari Bolen of Johns Hopkins University, Baltimore, and colleagues.

The researchers analyzed safety and efficacy data from 216 controlled clinical trials and cohort studies of oral diabetes agents, along with two systematic reviews. The studies and reviews were selected from published reports in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and from unpublished reports from industry and the Food and Drug Administration.

“Each oral diabetes agent is associated with adverse events that counterbalance its benefits,” wrote Dr. Bolen and colleagues. “Overall, metformin seemed to have the best profile of benefit to risk.” The American Diabetes Association favors metformin as initial pharmacotherapy for type 2 diabetes, although the choice of therapy often depends upon patient comorbidities.

Metformin and second-generation sulfonylureas were generally as effective as newer agents in improving intermediate outcomes. As monotherapy, all oral diabetes agents had similar effects on glycemic control, with an absolute reduction in hemoglobin A_1c levels of about 1 percentage point. The effects on glycemic control were additive when oral diabetes agents were used in combination therapy. The various agents did not differ significantly in their effect on systolic or diastolic blood pressure.

Only thiazolidinediones improved HDL-cholesterol levels, with a relative mean increase of 0.08–0.13 mmol/L, compared with treatment with other agents. However, thiazolidinediones also increased LDL cholesterol levels by a relative mean increase of 0.26 mmol/L. Metformin improved LDL cholesterol levels by a mean decrease of 0.26 mmol/L. Other oral diabetes agents did not appear to affect LDL cholesterol levels.

Metformin treatment was not associated with weight gain, compared with other agents or placebo. Acarbose treatment also did not lead to weight gain, compared with placebo. Weight gains ranging from 1 to 5 kg were seen with most other oral diabetes medications: thiazolidinediones, repaglinide, and second-generation sulfonylureas. They found no evidence of increased risk of lactic acidosis with metformin, compared with other oral diabetes agents. Hypoglycemic episodes occurred more frequently with second-generation sulfonylureas and repaglinide than with metformin or thiazolidinediones, although there was wide variation in the risk levels reported from the different clinical trials. Gastrointestinal symptoms were most frequent with metformin treatment, ranging from 2% to 63%, a higher rate than most other agents.

In short-term randomized trials, greater risk of congestive heart failure was seen with thiazolidinediones, compared with second-generation sulfonylureas or metformin. The absolute risk of congestive heart failure ranged from 0.8% to 3.6% for thiazolidinediones and from 0% to 2.6% for other oral diabetes agents. In placebo-controlled trials and cohort studies neither second-generation sulfonylureas nor metformin showed increased risk of congestive heart failure.

Because few studies have analyzed major clinical outcomes, data were insufficient for a thorough comparison of the effects of various oral diabetes agents on cardiovascular morbidity and mortality, microvascular outcomes, neuropathy, or death from any cause. “Large, long-term comparative studies on major clinical end points, such as myocardial infarction, chronic kidney disease, and cardiovascular mortality, are needed to determine definitively the comparative effects of the oral diabetes agents, especially in light of recent controversy regarding rosiglitazone,” they wrote.

In an interview, Dr. Zachary Bloomgarden of Mount Sinai School of Medicine in New York, agreed with the researchers' conclusion that the various agents have similar glucose-lowering events but challenged their conclusion that metformin is not associated with increased risk of lactic acidosis, citing toxicology evidence from numerous animal studies. The review “appears not to address much of the relevant information on this immense topic.”

Dr. Bloomgarden has served as a consultant for Merck and on speaker panels for Takeda, GlaxoSmithKline, Novo Nordisk, Eli Lilly, Amylin, Merck, and Novartis.

Metformin and second-generation sulfonylureas appear to be as safe and effective as the newer, more expensive oral diabetes drugs in the treatment of type 2 diabetes in adults, according to Dr. Shari Bolen of Johns Hopkins University, Baltimore, and colleagues.

The researchers analyzed safety and efficacy data from 216 controlled clinical trials and cohort studies of oral diabetes agents, along with two systematic reviews. The studies and reviews were selected from published reports in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and from unpublished reports from industry and the Food and Drug Administration.

“Each oral diabetes agent is associated with adverse events that counterbalance its benefits,” wrote Dr. Bolen and colleagues in a report published online in advance of its inclusion in the September 18 print edition of Annals of Internal Medicine. “Overall, metformin seemed to have the best profile of benefit to risk.” The American Diabetes Association favors metformin as initial pharmacotherapy for type 2 diabetes, although the choice of therapy often depends upon patient comorbidities.

Metformin and second-generation sulfonylureas were generally as effective as newer agents in improving intermediate outcomes. As monotherapy, all oral diabetes agents had similar effects on glycemic control, with an absolute reduction in hemoglobin A1c levels of approximately 1 percentage point. The effects on glycemic control were additive when oral diabetes agents were used in combination therapy. The various agents did not differ significantly in their effect on blood pressure.

Only thiazolidinediones improved HDL cholesterol levels, with a relative mean increase of 0.08–0.13 mmol/L, compared with treatment with other agents. However, thiazolidinediones also increased LDL cholesterol levels by a relative mean increase of 0.26 mmol/L. Metformin improved LDL cholesterol levels by a mean decrease of 0.26 mmol/L.

Metformin treatment was not associated with weight gain, compared with other agents or placebo. Acarbose treatment also did not lead to weight gain, compared with placebo. Weight gains ranging from 1 to 5 kg were seen with most other oral diabetes medications: thiazolidinediones, repaglinide, and second-generation sulfonylureas. Hypoglycemic episodes occurred more frequently with second-generation sulfonylureas and repaglinide than with metformin or thiazolidinediones, although there was wide variation in the risk levels reported from the different clinical trials.

In short-term randomized trials, greater risk of congestive heart failure was seen with thiazolidinediones, compared with second-generation sulfonylureas or metformin. The absolute risk of congestive heart failure ranged from 0.8% to 3.6% for thiazolidinediones and from 0% to 2.6% for other oral diabetes agents. In placebo-controlled trials and cohort studies neither second-generation sulfonylureas nor metformin showed increased risk of congestive heart failure.

Because few studies have analyzed major clinical outcomes, data were insufficient for a thorough comparison of the effects of various oral diabetes agents on cardiovascular morbidity and mortality, microvascular outcomes, neuropathy, or death from any cause. “Large, long-term comparative studies on major clinical end points, such as myocardial infarction, chronic kidney disease, and cardiovascular mortality, are needed to determine definitively the comparative effects of the oral diabetes agents, especially in light of recent controversy regarding rosiglitazone,” wrote the authors.

Dr. Zachary Bloomgarden of Mount Sinai School of Medicine in New York disagreed with the analytical design used by the study authors and disputes some of the study's findings.

“The authors are correct in their conclusion that the various agents have similar glucose-lowering events,” Dr. Bloomgarden said in an interview. However, he challenged their conclusion that metformin is not associated with increased risk of lactic acidosis, citing toxicology evidence from numerous animal studies.

The question of whether thiazolidinediones might have a beneficial effect in improving cardiovascular outcome was not thoroughly examined, according to Dr. Bloomgarden. The review “appears not to address much of the relevant information on this immense topic,” he said. “I would question whether its conclusions should be considered accurate.”

Dr. Bloomgarden has served as a consultant for Merck and on speaker panels for Takeda, GlaxoSmithKline, Novo Nordisk, Eli Lilly, Amylin, Merck, and Novartis.

Metformin and second-generation sulfonylureas appear to be as safe and effective as the newer, more expensive oral diabetes drugs in the treatment of type 2 diabetes in adults, according to Dr. Shari Bolen of Johns Hopkins University, Baltimore, and colleagues.

The researchers analyzed safety and efficacy data from 216 controlled clinical trials and cohort studies of oral diabetes agents, along with two systematic reviews. The studies and reviews were selected from published reports in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and from unpublished reports from industry and the Food and Drug Administration.

“Each oral diabetes agent is associated with adverse events that counterbalance its benefits,” wrote Dr. Bolen and colleagues in a report published online in advance of its inclusion in the September 18 print edition of Annals of Internal Medicine. “Overall, metformin seemed to have the best profile of benefit to risk.” The American Diabetes Association favors metformin as initial pharmacotherapy for type 2 diabetes, although the choice of therapy often depends upon patient comorbidities.

Metformin and second-generation sulfonylureas were generally as effective as newer agents in improving intermediate outcomes. As monotherapy, all oral diabetes agents had similar effects on glycemic control, with an absolute reduction in hemoglobin A1c levels of approximately 1 percentage point. The effects on glycemic control were additive when oral diabetes agents were used in combination therapy. The various agents did not differ significantly in their effect on blood pressure.

Only thiazolidinediones improved HDL cholesterol levels, with a relative mean increase of 0.08–0.13 mmol/L, compared with treatment with other agents. However, thiazolidinediones also increased LDL cholesterol levels by a relative mean increase of 0.26 mmol/L. Metformin improved LDL cholesterol levels by a mean decrease of 0.26 mmol/L.

Metformin treatment was not associated with weight gain, compared with other agents or placebo. Acarbose treatment also did not lead to weight gain, compared with placebo. Weight gains ranging from 1 to 5 kg were seen with most other oral diabetes medications: thiazolidinediones, repaglinide, and second-generation sulfonylureas. Hypoglycemic episodes occurred more frequently with second-generation sulfonylureas and repaglinide than with metformin or thiazolidinediones, although there was wide variation in the risk levels reported from the different clinical trials.

In short-term randomized trials, greater risk of congestive heart failure was seen with thiazolidinediones, compared with second-generation sulfonylureas or metformin. The absolute risk of congestive heart failure ranged from 0.8% to 3.6% for thiazolidinediones and from 0% to 2.6% for other oral diabetes agents. In placebo-controlled trials and cohort studies neither second-generation sulfonylureas nor metformin showed increased risk of congestive heart failure.

Because few studies have analyzed major clinical outcomes, data were insufficient for a thorough comparison of the effects of various oral diabetes agents on cardiovascular morbidity and mortality, microvascular outcomes, neuropathy, or death from any cause. “Large, long-term comparative studies on major clinical end points, such as myocardial infarction, chronic kidney disease, and cardiovascular mortality, are needed to determine definitively the comparative effects of the oral diabetes agents, especially in light of recent controversy regarding rosiglitazone,” wrote the authors.

Dr. Zachary Bloomgarden of Mount Sinai School of Medicine in New York disagreed with the analytical design used by the study authors and disputes some of the study's findings.

“The authors are correct in their conclusion that the various agents have similar glucose-lowering events,” Dr. Bloomgarden said in an interview. However, he challenged their conclusion that metformin is not associated with increased risk of lactic acidosis, citing toxicology evidence from numerous animal studies.

The question of whether thiazolidinediones might have a beneficial effect in improving cardiovascular outcome was not thoroughly examined, according to Dr. Bloomgarden. The review “appears not to address much of the relevant information on this immense topic,” he said. “I would question whether its conclusions should be considered accurate.”

Dr. Bloomgarden has served as a consultant for Merck and on speaker panels for Takeda, GlaxoSmithKline, Novo Nordisk, Eli Lilly, Amylin, Merck, and Novartis.

Metformin and second-generation sulfonylureas appear to be as safe and effective as the newer, more expensive oral diabetes drugs in the treatment of type 2 diabetes in adults, according to Dr. Shari Bolen of Johns Hopkins University, Baltimore, and colleagues.

The researchers analyzed safety and efficacy data from 216 controlled clinical trials and cohort studies of oral diabetes agents, along with two systematic reviews. The studies and reviews were selected from published reports in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and from unpublished reports from industry and the Food and Drug Administration.

“Each oral diabetes agent is associated with adverse events that counterbalance its benefits,” wrote Dr. Bolen and colleagues in a report published online in advance of its inclusion in the September 18 print edition of Annals of Internal Medicine. “Overall, metformin seemed to have the best profile of benefit to risk.” The American Diabetes Association favors metformin as initial pharmacotherapy for type 2 diabetes, although the choice of therapy often depends upon patient comorbidities.

Metformin and second-generation sulfonylureas were generally as effective as newer agents in improving intermediate outcomes. As monotherapy, all oral diabetes agents had similar effects on glycemic control, with an absolute reduction in hemoglobin A1c levels of approximately 1 percentage point. The effects on glycemic control were additive when oral diabetes agents were used in combination therapy. The various agents did not differ significantly in their effect on blood pressure.

Only thiazolidinediones improved HDL cholesterol levels, with a relative mean increase of 0.08–0.13 mmol/L, compared with treatment with other agents. However, thiazolidinediones also increased LDL cholesterol levels by a relative mean increase of 0.26 mmol/L. Metformin improved LDL cholesterol levels by a mean decrease of 0.26 mmol/L.

Metformin treatment was not associated with weight gain, compared with other agents or placebo. Acarbose treatment also did not lead to weight gain, compared with placebo. Weight gains ranging from 1 to 5 kg were seen with most other oral diabetes medications: thiazolidinediones, repaglinide, and second-generation sulfonylureas. Hypoglycemic episodes occurred more frequently with second-generation sulfonylureas and repaglinide than with metformin or thiazolidinediones, although there was wide variation in the risk levels reported from the different clinical trials.

In short-term randomized trials, greater risk of congestive heart failure was seen with thiazolidinediones, compared with second-generation sulfonylureas or metformin. The absolute risk of congestive heart failure ranged from 0.8% to 3.6% for thiazolidinediones and from 0% to 2.6% for other oral diabetes agents. In placebo-controlled trials and cohort studies neither second-generation sulfonylureas nor metformin showed increased risk of congestive heart failure.

Because few studies have analyzed major clinical outcomes, data were insufficient for a thorough comparison of the effects of various oral diabetes agents on cardiovascular morbidity and mortality, microvascular outcomes, neuropathy, or death from any cause. “Large, long-term comparative studies on major clinical end points, such as myocardial infarction, chronic kidney disease, and cardiovascular mortality, are needed to determine definitively the comparative effects of the oral diabetes agents, especially in light of recent controversy regarding rosiglitazone,” wrote the authors.

Dr. Zachary Bloomgarden of Mount Sinai School of Medicine in New York disagreed with the analytical design used by the study authors and disputes some of the study's findings.

“The authors are correct in their conclusion that the various agents have similar glucose-lowering events,” Dr. Bloomgarden said in an interview. However, he challenged their conclusion that metformin is not associated with increased risk of lactic acidosis, citing toxicology evidence from numerous animal studies.

The question of whether thiazolidinediones might have a beneficial effect in improving cardiovascular outcome was not thoroughly examined, according to Dr. Bloomgarden. The review “appears not to address much of the relevant information on this immense topic,” he said. “I would question whether its conclusions should be considered accurate.”

Dr. Bloomgarden has served as a consultant for Merck and on speaker panels for Takeda, GlaxoSmithKline, Novo Nordisk, Eli Lilly, Amylin, Merck, and Novartis.

SANTIAGO, CHILE — Risk factors affecting a person's vulnerability to posttraumatic stress disorder (PTSD) include factors associated with personal experiences as well as genetic or heritable factors, Rachel Yehuda, Ph.D., said at an international congress sponsored by the World Federation of Societies of Biological Psychiatry.

Trauma can cause symptoms in offspring even though the trauma is experienced vicariously, Dr. Yehuda said. Vulnerability to stress can be biologically transmitted, either through genetic susceptibility or possibly by epigenetic transmission.

Low cortisol levels are associated with PTSD. As might be expected, cortisol levels have been shown to be low in high-risk PTSD subjects immediately after trauma, or in those who actually develop PTSD at follow-up, Dr. Yehuda said. In studies involving adult children of Holocaust survivors, for example, Dr. Yehuda and her colleagues have shown that cortisol levels were significantly lower in the offspring of Holocaust survivors who had PTSD, compared with those whose parents did not have PTSD.

Follow-up studies have shown that maternal, not paternal, PTSD is relevant to cortisol effects in the offspring, said Dr. Yehuda, professor of psychiatry at the Mount Sinai School of Medicine and the James J. Peters VA Medical Center, both in New York.

In a study of women who were pregnant during the Sept. 11, 2001, terrorist attacks in New York City, Dr. Yehuda and her colleagues found that the infants of mothers with PTSD had lower cortisol levels than did infants of those without PTSD (J. Clin. Endocrinol. Metab. 2005;90:4115–8).

Normally, the sympathetic arousal associated with the acute stress decreases over time, and the individual can recall the traumatic event without experiencing physiologic responses. In some people, though, recovery does not take place, and PTSD occurs—sometimes months or even years after the traumatic event.

Early experiences influence the subjective interpretation of events. A person's response to trauma may resemble those of his parents, Dr. Yehuda said. Parents transmit perspectives about the world to their offspring. As a result, parents who suffer from PTSD may have deficits in parenting, and children can “learn” symptoms of stress from their parents.

Subjective interpretation of an event largely determines whether that event is traumatic to a person. What the subject thinks about the event—including why it happened and what could have been done differently—affects the response to trauma. A subject who blames herself for rape, or a subject who feels that an event occurred as punishment from God, may be more likely to experience PTSD than will someone who regards his involvement in the traumatic event as a matter of chance.

PTSD has been recognized as a diagnosis since the publication of the DSM-III. “In the beginning when PTSD was first established, the idea really was to have a diagnostic entity that would explain long-term response to a traumatic event, and the discussions were about what kind of event would give [rise to] PTSD,” Dr. Yehuda said. What has become clear is that most people who are exposed to trauma do not develop this disorder, she noted; “PTSD does occur frequently, but it is more likely not to occur, no matter what traumatic event we are talking about.”

Consequently, the focus has switched from a definition of which traumatic events lead to PTSD to a definition of why some people are more vulnerable, or less resistant, than others to the long-term effects of trauma. Risk factors that affect vulnerability to PTSD include posttraumatic factors, such as retraumatization and lack of social support. Event characteristics, such as injury or intense emotional responses associated with the traumatic event, are pretraumatic factors that can increase the likelihood of PTSD.

In an effort to identify those with greater vulnerability to PTSD, Dr. Yehuda's research has focused on characterizing pretraumatic factors that may contribute to a person's reaction of intense distress.

Unresolved issues in the field of PTSD research include whether there are distinct biologic correlates of different risk factors for PTSD and whether a biologic “final common pathway” exists representing PTSD, Dr. Yehuda said.

SANTIAGO, CHILE — Risk factors affecting a person's vulnerability to posttraumatic stress disorder (PTSD) include factors associated with personal experiences as well as genetic or heritable factors, Rachel Yehuda, Ph.D., said at an international congress sponsored by the World Federation of Societies of Biological Psychiatry.

Trauma can cause symptoms in offspring even though the trauma is experienced vicariously, Dr. Yehuda said. Vulnerability to stress can be biologically transmitted, either through genetic susceptibility or possibly by epigenetic transmission.

Low cortisol levels are associated with PTSD. As might be expected, cortisol levels have been shown to be low in high-risk PTSD subjects immediately after trauma, or in those who actually develop PTSD at follow-up, Dr. Yehuda said. In studies involving adult children of Holocaust survivors, for example, Dr. Yehuda and her colleagues have shown that cortisol levels were significantly lower in the offspring of Holocaust survivors who had PTSD, compared with those whose parents did not have PTSD.

Follow-up studies have shown that maternal, not paternal, PTSD is relevant to cortisol effects in the offspring, said Dr. Yehuda, professor of psychiatry at the Mount Sinai School of Medicine and the James J. Peters VA Medical Center, both in New York.

In a study of women who were pregnant during the Sept. 11, 2001, terrorist attacks in New York City, Dr. Yehuda and her colleagues found that the infants of mothers with PTSD had lower cortisol levels than did infants of those without PTSD (J. Clin. Endocrinol. Metab. 2005;90:4115–8).

Normally, the sympathetic arousal associated with the acute stress decreases over time, and the individual can recall the traumatic event without experiencing physiologic responses. In some people, though, recovery does not take place, and PTSD occurs—sometimes months or even years after the traumatic event.

Early experiences influence the subjective interpretation of events. A person's response to trauma may resemble those of his parents, Dr. Yehuda said. Parents transmit perspectives about the world to their offspring. As a result, parents who suffer from PTSD may have deficits in parenting, and children can “learn” symptoms of stress from their parents.

Subjective interpretation of an event largely determines whether that event is traumatic to a person. What the subject thinks about the event—including why it happened and what could have been done differently—affects the response to trauma. A subject who blames herself for rape, or a subject who feels that an event occurred as punishment from God, may be more likely to experience PTSD than will someone who regards his involvement in the traumatic event as a matter of chance.

PTSD has been recognized as a diagnosis since the publication of the DSM-III. “In the beginning when PTSD was first established, the idea really was to have a diagnostic entity that would explain long-term response to a traumatic event, and the discussions were about what kind of event would give [rise to] PTSD,” Dr. Yehuda said. What has become clear is that most people who are exposed to trauma do not develop this disorder, she noted; “PTSD does occur frequently, but it is more likely not to occur, no matter what traumatic event we are talking about.”

Consequently, the focus has switched from a definition of which traumatic events lead to PTSD to a definition of why some people are more vulnerable, or less resistant, than others to the long-term effects of trauma. Risk factors that affect vulnerability to PTSD include posttraumatic factors, such as retraumatization and lack of social support. Event characteristics, such as injury or intense emotional responses associated with the traumatic event, are pretraumatic factors that can increase the likelihood of PTSD.

In an effort to identify those with greater vulnerability to PTSD, Dr. Yehuda's research has focused on characterizing pretraumatic factors that may contribute to a person's reaction of intense distress.

Unresolved issues in the field of PTSD research include whether there are distinct biologic correlates of different risk factors for PTSD and whether a biologic “final common pathway” exists representing PTSD, Dr. Yehuda said.

SANTIAGO, CHILE — Risk factors affecting a person's vulnerability to posttraumatic stress disorder (PTSD) include factors associated with personal experiences as well as genetic or heritable factors, Rachel Yehuda, Ph.D., said at an international congress sponsored by the World Federation of Societies of Biological Psychiatry.

Trauma can cause symptoms in offspring even though the trauma is experienced vicariously, Dr. Yehuda said. Vulnerability to stress can be biologically transmitted, either through genetic susceptibility or possibly by epigenetic transmission.

Low cortisol levels are associated with PTSD. As might be expected, cortisol levels have been shown to be low in high-risk PTSD subjects immediately after trauma, or in those who actually develop PTSD at follow-up, Dr. Yehuda said. In studies involving adult children of Holocaust survivors, for example, Dr. Yehuda and her colleagues have shown that cortisol levels were significantly lower in the offspring of Holocaust survivors who had PTSD, compared with those whose parents did not have PTSD.

Follow-up studies have shown that maternal, not paternal, PTSD is relevant to cortisol effects in the offspring, said Dr. Yehuda, professor of psychiatry at the Mount Sinai School of Medicine and the James J. Peters VA Medical Center, both in New York.

In a study of women who were pregnant during the Sept. 11, 2001, terrorist attacks in New York City, Dr. Yehuda and her colleagues found that the infants of mothers with PTSD had lower cortisol levels than did infants of those without PTSD (J. Clin. Endocrinol. Metab. 2005;90:4115–8).

Normally, the sympathetic arousal associated with the acute stress decreases over time, and the individual can recall the traumatic event without experiencing physiologic responses. In some people, though, recovery does not take place, and PTSD occurs—sometimes months or even years after the traumatic event.

Early experiences influence the subjective interpretation of events. A person's response to trauma may resemble those of his parents, Dr. Yehuda said. Parents transmit perspectives about the world to their offspring. As a result, parents who suffer from PTSD may have deficits in parenting, and children can “learn” symptoms of stress from their parents.

Subjective interpretation of an event largely determines whether that event is traumatic to a person. What the subject thinks about the event—including why it happened and what could have been done differently—affects the response to trauma. A subject who blames herself for rape, or a subject who feels that an event occurred as punishment from God, may be more likely to experience PTSD than will someone who regards his involvement in the traumatic event as a matter of chance.

PTSD has been recognized as a diagnosis since the publication of the DSM-III. “In the beginning when PTSD was first established, the idea really was to have a diagnostic entity that would explain long-term response to a traumatic event, and the discussions were about what kind of event would give [rise to] PTSD,” Dr. Yehuda said. What has become clear is that most people who are exposed to trauma do not develop this disorder, she noted; “PTSD does occur frequently, but it is more likely not to occur, no matter what traumatic event we are talking about.”

Consequently, the focus has switched from a definition of which traumatic events lead to PTSD to a definition of why some people are more vulnerable, or less resistant, than others to the long-term effects of trauma. Risk factors that affect vulnerability to PTSD include posttraumatic factors, such as retraumatization and lack of social support. Event characteristics, such as injury or intense emotional responses associated with the traumatic event, are pretraumatic factors that can increase the likelihood of PTSD.

In an effort to identify those with greater vulnerability to PTSD, Dr. Yehuda's research has focused on characterizing pretraumatic factors that may contribute to a person's reaction of intense distress.

Unresolved issues in the field of PTSD research include whether there are distinct biologic correlates of different risk factors for PTSD and whether a biologic “final common pathway” exists representing PTSD, Dr. Yehuda said.