Early- and Late-Onset Psoriasis Differ Genetically

SEOUL, SOUTH KOREA – Early- and late-onset psoriasis are genetically and immunologically distinct diseases that happen to look similar clinically, according to Dr. Christopher E. Griffiths.

"All the research funding in psoriasis that has been spent in trying to understand the genetics of the disease comes down to one key finding: early-onset psoriasis, occurring before age 40, is strikingly associated with the HLA-Cw6 allele or something close to it," Dr. Griffiths said at the World Congress of Dermatology.

The class I human leukocyte antigen, HLA-Cw6, is found in 55%-80% of patients with psoriasis beginning before the age of 40. Early-onset disease accounts for 75% of all cases of psoriasis.

Late-onset psoriasis peaks in occurrence at the ages of 55-60. The frequency of the HLA-Cw6 allele in patients with late-onset disease is 15%-20%, comparable to that in the general population, said Dr. Griffiths, professor of dermatology at the University of Manchester (England).

Multiple genetic studies have shown that guttate psoriasis is predominantly found in patients who are HLA-Cw6 positive. An Icelandic study found that Cw6-positive patients also tended to have more severe psoriasis, a greater incidence of Koebner’s phenomenon, and more extensive plaques on their trunk, arms, and legs, while Cw6-negative status was associated with an increased likelihood of nail dystrophy, psoriatic arthritis, and later age of psoriasis onset (J. Invest. Dermatol. 2002;118:362-5).

Dr. Griffiths and his coworkers demonstrated that patients with early- and late-onset psoriasis also differ in terms of epidermal Langerhans cell function. These cells comprise the outermost surveillance post of the immune system. They are tasked with identifying invading pathogens and foreign antigens and transporting them from the epidermis to draining lymph nodes. Normally, this migration to lymph nodes is highly dependent upon two cytokines: interleukin-1 (IL-1) beta and tumor necrosis factor (TNF).

Dr. Griffiths and his co-investigators demonstrated that epidermal Langerhans cell mobilization and migration are greatly impaired in nonlesional skin of early-onset psoriasis patients, as compared to individuals without psoriasis.

Intradermal injection of TNF-alpha or IL-1 beta stimulated Langerhans cell migration in patients without psoriasis, but it had little or no effect on Langerhans cell function in uninvolved skin of patients with early-onset psoriasis.

In contrast, Langerhans cell migration was normal in response to intradermal injection of IL-1 beta in uninvolved skin of late-onset psoriasis patients. However, Langerhans cell migration in nonlesional skin was impaired in response to administration of TNF-alpha in the patients with late-onset psoriasis (J. Invest. Dermatol. 2010;130:1940-2).

University of Utah investigators have identified two different forms of chronic plaque psoriasis based not upon genetic or immunologic distinctions, but upon plaque morphology. In a prospective study involving 500 patients in the Utah Psoriasis Initiative, 29% of subjects characterized their plaques as thick when their psoriasis was at its most severe, while 25% rated the plaques as thin.

Thick-plaque patients were more likely to be male and have a higher body mass index, larger plaques affecting a greater body surface area, and an increased likelihood of nail dystrophy and psoriatic arthritis. Patients with thin plaques were more likely to have an eczematous component, were more prone to develop skin cancer, and were more likely to have had guttate psoriasis at some stage (J. Invest. Dermatol. 2006;126:2397-413).

"Until we understand much more about the pathogenesis and the immunology and the genetics of psoriasis, this simple clinical characterization would actually be very helpful in the clinic," said Dr. Griffiths. "I had a medical student working with me a couple of summers ago whose main task was to classify the patterns of disease in all the patients we saw in our psoriasis clinic; he could reliably differentiate 10 different forms of chronic plaque psoriasis."

Soon, it may be possible to classify plaque psoriasis by molecular phenotyping, which will help in matching the best possible treatment for a given individual, he said.

Dr. Griffiths disclosed that he has been a consultant to or has received research funds from numerous companies that manufacture drugs used in treating psoriasis.

SEOUL, SOUTH KOREA – Early- and late-onset psoriasis are genetically and immunologically distinct diseases that happen to look similar clinically, according to Dr. Christopher E. Griffiths.

"All the research funding in psoriasis that has been spent in trying to understand the genetics of the disease comes down to one key finding: early-onset psoriasis, occurring before age 40, is strikingly associated with the HLA-Cw6 allele or something close to it," Dr. Griffiths said at the World Congress of Dermatology.

The class I human leukocyte antigen, HLA-Cw6, is found in 55%-80% of patients with psoriasis beginning before the age of 40. Early-onset disease accounts for 75% of all cases of psoriasis.

Late-onset psoriasis peaks in occurrence at the ages of 55-60. The frequency of the HLA-Cw6 allele in patients with late-onset disease is 15%-20%, comparable to that in the general population, said Dr. Griffiths, professor of dermatology at the University of Manchester (England).

Multiple genetic studies have shown that guttate psoriasis is predominantly found in patients who are HLA-Cw6 positive. An Icelandic study found that Cw6-positive patients also tended to have more severe psoriasis, a greater incidence of Koebner’s phenomenon, and more extensive plaques on their trunk, arms, and legs, while Cw6-negative status was associated with an increased likelihood of nail dystrophy, psoriatic arthritis, and later age of psoriasis onset (J. Invest. Dermatol. 2002;118:362-5).

Dr. Griffiths and his coworkers demonstrated that patients with early- and late-onset psoriasis also differ in terms of epidermal Langerhans cell function. These cells comprise the outermost surveillance post of the immune system. They are tasked with identifying invading pathogens and foreign antigens and transporting them from the epidermis to draining lymph nodes. Normally, this migration to lymph nodes is highly dependent upon two cytokines: interleukin-1 (IL-1) beta and tumor necrosis factor (TNF).

Dr. Griffiths and his co-investigators demonstrated that epidermal Langerhans cell mobilization and migration are greatly impaired in nonlesional skin of early-onset psoriasis patients, as compared to individuals without psoriasis.

Intradermal injection of TNF-alpha or IL-1 beta stimulated Langerhans cell migration in patients without psoriasis, but it had little or no effect on Langerhans cell function in uninvolved skin of patients with early-onset psoriasis.

In contrast, Langerhans cell migration was normal in response to intradermal injection of IL-1 beta in uninvolved skin of late-onset psoriasis patients. However, Langerhans cell migration in nonlesional skin was impaired in response to administration of TNF-alpha in the patients with late-onset psoriasis (J. Invest. Dermatol. 2010;130:1940-2).

University of Utah investigators have identified two different forms of chronic plaque psoriasis based not upon genetic or immunologic distinctions, but upon plaque morphology. In a prospective study involving 500 patients in the Utah Psoriasis Initiative, 29% of subjects characterized their plaques as thick when their psoriasis was at its most severe, while 25% rated the plaques as thin.

Thick-plaque patients were more likely to be male and have a higher body mass index, larger plaques affecting a greater body surface area, and an increased likelihood of nail dystrophy and psoriatic arthritis. Patients with thin plaques were more likely to have an eczematous component, were more prone to develop skin cancer, and were more likely to have had guttate psoriasis at some stage (J. Invest. Dermatol. 2006;126:2397-413).

"Until we understand much more about the pathogenesis and the immunology and the genetics of psoriasis, this simple clinical characterization would actually be very helpful in the clinic," said Dr. Griffiths. "I had a medical student working with me a couple of summers ago whose main task was to classify the patterns of disease in all the patients we saw in our psoriasis clinic; he could reliably differentiate 10 different forms of chronic plaque psoriasis."

Soon, it may be possible to classify plaque psoriasis by molecular phenotyping, which will help in matching the best possible treatment for a given individual, he said.

Dr. Griffiths disclosed that he has been a consultant to or has received research funds from numerous companies that manufacture drugs used in treating psoriasis.

SEOUL, SOUTH KOREA – Early- and late-onset psoriasis are genetically and immunologically distinct diseases that happen to look similar clinically, according to Dr. Christopher E. Griffiths.

"All the research funding in psoriasis that has been spent in trying to understand the genetics of the disease comes down to one key finding: early-onset psoriasis, occurring before age 40, is strikingly associated with the HLA-Cw6 allele or something close to it," Dr. Griffiths said at the World Congress of Dermatology.

The class I human leukocyte antigen, HLA-Cw6, is found in 55%-80% of patients with psoriasis beginning before the age of 40. Early-onset disease accounts for 75% of all cases of psoriasis.

Late-onset psoriasis peaks in occurrence at the ages of 55-60. The frequency of the HLA-Cw6 allele in patients with late-onset disease is 15%-20%, comparable to that in the general population, said Dr. Griffiths, professor of dermatology at the University of Manchester (England).

Multiple genetic studies have shown that guttate psoriasis is predominantly found in patients who are HLA-Cw6 positive. An Icelandic study found that Cw6-positive patients also tended to have more severe psoriasis, a greater incidence of Koebner’s phenomenon, and more extensive plaques on their trunk, arms, and legs, while Cw6-negative status was associated with an increased likelihood of nail dystrophy, psoriatic arthritis, and later age of psoriasis onset (J. Invest. Dermatol. 2002;118:362-5).

Dr. Griffiths and his coworkers demonstrated that patients with early- and late-onset psoriasis also differ in terms of epidermal Langerhans cell function. These cells comprise the outermost surveillance post of the immune system. They are tasked with identifying invading pathogens and foreign antigens and transporting them from the epidermis to draining lymph nodes. Normally, this migration to lymph nodes is highly dependent upon two cytokines: interleukin-1 (IL-1) beta and tumor necrosis factor (TNF).

Dr. Griffiths and his co-investigators demonstrated that epidermal Langerhans cell mobilization and migration are greatly impaired in nonlesional skin of early-onset psoriasis patients, as compared to individuals without psoriasis.

Intradermal injection of TNF-alpha or IL-1 beta stimulated Langerhans cell migration in patients without psoriasis, but it had little or no effect on Langerhans cell function in uninvolved skin of patients with early-onset psoriasis.

In contrast, Langerhans cell migration was normal in response to intradermal injection of IL-1 beta in uninvolved skin of late-onset psoriasis patients. However, Langerhans cell migration in nonlesional skin was impaired in response to administration of TNF-alpha in the patients with late-onset psoriasis (J. Invest. Dermatol. 2010;130:1940-2).

University of Utah investigators have identified two different forms of chronic plaque psoriasis based not upon genetic or immunologic distinctions, but upon plaque morphology. In a prospective study involving 500 patients in the Utah Psoriasis Initiative, 29% of subjects characterized their plaques as thick when their psoriasis was at its most severe, while 25% rated the plaques as thin.

Thick-plaque patients were more likely to be male and have a higher body mass index, larger plaques affecting a greater body surface area, and an increased likelihood of nail dystrophy and psoriatic arthritis. Patients with thin plaques were more likely to have an eczematous component, were more prone to develop skin cancer, and were more likely to have had guttate psoriasis at some stage (J. Invest. Dermatol. 2006;126:2397-413).

"Until we understand much more about the pathogenesis and the immunology and the genetics of psoriasis, this simple clinical characterization would actually be very helpful in the clinic," said Dr. Griffiths. "I had a medical student working with me a couple of summers ago whose main task was to classify the patterns of disease in all the patients we saw in our psoriasis clinic; he could reliably differentiate 10 different forms of chronic plaque psoriasis."

Soon, it may be possible to classify plaque psoriasis by molecular phenotyping, which will help in matching the best possible treatment for a given individual, he said.

Dr. Griffiths disclosed that he has been a consultant to or has received research funds from numerous companies that manufacture drugs used in treating psoriasis.