Psoriasis Treatment
The history of the treatment psoriasis is relatively short, and initially treatment discoveries were serendipitous. Early psoriasis therapies included arsenic and ammoniated mercury use in the 19th Century. In the first half of the 20th Century, anthralin and tar were discovered as effective psoriasis treatments. Corticosteroids were developed in the 1950s. These therapies were followed in the 1970s by use of methotrexate and PUVA on psoriasis. In the 1980s, psoriasis treatment discoveries included narrowband UVB, retinoids, and vitamin D therapies. From the 1990s to the present time, manipulating the immune system to treat psoriasis has been explored first with cyclosporine and more recently with targeted molecules.
19th Century – Arsenic and ammoniated mercury
Throughout history, arsenic has been utilized as both a poison and therapeutic. In 1806, Girdlestone reported on the efficacy of Fowler’s Solution with 1% arsenic in treating many dermatologic conditions including psoriasis. With similar toxic potential, ammoniated mercury was used as a medication before the 20th Century. In 1876, Duhring recommended mercurial ointments to treat psoriasis.
1900–1950s – Anthralin and tar
In 1876, Squire inadvertently discovered anthralin as a treatment psoriasis. Squire prescribed Goa powder, which was until then known only to be effective in ringworm, and the patient’s psoriasis improved. The active ingredient of Goa powder is chrysarobin, also known as 2-methyl dithranol. During World War I, this treatment was further refined, as a synthetic form of chrysarobin called antralin, or dithranol, was formed. In 1916, Unna reported the effectiveness of dithranol as an antipsoriatic treatment.
The next advancement in psoriasis treatment was coal tar. Hippocrates andother ancient physicians treated dermatologic conditions with pine tar and other types of tar. Coal tar became available when coal gas production developedin the late 19th Century, and Goeckerman found that coal tar was particularly useful in psoriasis therapy. Many observed that psoriasis improved with summer sun. In 1925, Goeckerman reported an additive benefit of coal tar and UVB radiation in psoriasis treatment. Goeckerman’s method remained the mainstay of psoriasis treatment for decades. In 1953, Ingram reported the successful treatment of psoriasis with a combination of Unna and Goeckerman’s modalities. He established the first day care center for psoriasis in which patients were treated with a tar bath, then UVB therapy, and lastly with 0.42% dithranol in Lassar’s paste. This treatment improved the morbidity of psoriasis for many patients, but was time intensive.
1950s – Corticosteroids
In the 1950s, the corticosteroid era began and revolutionized the treatment of many diseases. In 1950 Hench, Kendall, and Reichstein received the Nobel Prize for the development of cortisone. A mere 2 years later, Sulzberg and Witten reported that compound F, or hydrocortisone, was the first moderately successful topical corticosteroid in inflammatory skin diseases including psoriasis. From that time forward, additional topical corticosteroid preparations were developed to treat inflammatory dermatoses such as psoriasis.
1970s – Methotrexate and PUVA
Although methotrexate was first developed in the 1950s, it was not used to treat psoriasis until the 1970s. In 1946, Farber developed aminopterin to treat leukemia [40]. Five years later, Gubner reported that aminopterin used in the treatment of rheumatoid arthritis also cleared psoriasis. In 1958, Edmundsun and Guy introduced methotrexate, a more stable derivative of aminopterin with lower toxicity [41]. Investigators initially believed that folic acid antagonists prevented keratinocyte hyperproliferation, but later the effect on lymphocytes in psoriatic lesions was elucidated. In 1972, the FDA finally approved the use of methotrexate for psoriasis.
Also in the 1970s, PUVA therapy was reported to be effective in psoriasis. PUVA, based on the interaction between UV radiation and a photo-sensitizing chemical, has its own rich history. The concept originated in about 1'500 BC when Egyptian healers treated vitiligo with a combination of sunlight and ingestion of plants known as psoralens, including fig and limes. An article published in 1974 reported the efficacy of oral PUVA therapy in a group of patients with psoriasis. Three years later, a multi-center study confirmed that most patients with psoriasis experienced clearing of their skin using oralPUVA. Shortly after the development of oral PUVA, alternative bathwater delivery systems of psoralens were also created to minimize adverse effects associated with oral PUVA.
1980s – Narrowband UVB, retinoids, vitamin D
Although often therapeutically successful, PUVA therapy carries an increased risk of skin cancer. Therefore, further study of UVB therapy was undertaken. In 1981, Parrish and Jaenicke demonstrated that UVB wavelengths between 300 and 313 nm caused the greatest remission of skin lesions. Subsequent trials reported that the 311 nm spectrum showed improved clearance of lesions with less erythema.
In the 1980s, researchers also established the use of retinoids in psoriasis treatment. Prior to its use in psoriasis, in the 1960s physicians prescribed retinoids for hyperkeratosis and acne. At this time, first-generation and synthetic topical retinoids did not have significant antipsoriatic activity. In the early 1980s, reports demonstrated the efficacy of the second-generation retinoids etretinate and its derivative acitretin, in the treatment psoriasis. Although etretinate is no longer available in the US due to its lipophilia and protracted adverse effects, acitretin has a shorter half life and remains an important therapy in psoriasis. Third-generation acetylenic retinoids developed in the 1980s allowed for the production of a topical retinoid, tazarotene, with demonstrated anti-psoriatic efficacy.
The next class of drugs developed for psoriasis, vitamin D and its analogs, was also developed by chance observations in the 1980s. In 1985, a patient who received oral vitamin D3 for osteoporosis experienced dramatic improvement of his psoriasis. The active form of vitamin D3 plays a part in the control of intestinal calcium absorption, bone mineralization, keratinocyte differentiation, keratinocyte proliferation, and immune modulation. Despite extensive research, the exact mechanism of action of vitamin D analogs remains unknown. In 1988, a topical form of vitamin D proved useful in the treatment psoriasis.
1990s – Cyclic immunosuppressive medications
In 1997, cyclosporine was FDA approved for psoriasis treatment. Cyclosporine was isolated in 1969 from a fungus and was screened for antibiotic properties. In 1976, Borel reported immunosuppressive properties of cyclosporine in animal models. Three years later, Cyclosporine A was used experimentally in transplant patients to prevent graft rejection, and psoriatic patients in these trials experienced relief of their lesions. FDA approval was delayed until the 1990s due to concerns about toxicity. Cyclosporine is prescribed for severe psoriasis that is not responsive to other therapies.
Psoriasis Treatmen
The history of the treatment psoriasis is relatively short, and initially treatment discoveries were serendipitous. Early psoriasis therapies included arsenic and ammoniated mercury use in the 19th Century. In the first half of the 20th Century, anthralin and tar were discovered as effective psoriasis treatments. Corticosteroids were developed in the 1950s. These therapies were followed in the 1970s by use of methotrexate and PUVA on psoriasis. In the 1980s, psoriasis treatment discoveries included narrowband UVB, retinoids, and vitamin D therapies. From the 1990s to the present time, manipulating the immune system to treat psoriasis has been explored first with cyclosporine and more recently with targeted molecules.
19th Century – Arsenic and ammoniated mercury
Throughout history, arsenic has been utilized as both a poison and therapeutic. In 1806, Girdlestone reported on the efficacy of Fowler’s Solution with 1% arsenic in treating many dermatologic conditions including psoriasis. With similar toxic potential, ammoniated mercury was used as a medication before the 20th Century. In 1876, Duhring recommended mercurial ointments to treat psoriasis.
1900–1950s – Anthralin and tar
In 1876, Squire inadvertently discovered anthralin as a treatment psoriasis. Squire prescribed Goa powder, which was until then known only to be effective in ringworm, and the patient’s psoriasis improved. The active ingredient of Goa powder is chrysarobin, also known as 2-methyl dithranol. During World War I, this treatment was further refined, as a synthetic form of chrysarobin called antralin, or dithranol, was formed. In 1916, Unna reported the effectiveness of dithranol as an antipsoriatic treatment.
The next advancement in psoriasis treatment was coal tar. Hippocrates andother ancient physicians treated dermatologic conditions with pine tar and other types of tar. Coal tar became available when coal gas production developedin the late 19th Century, and Goeckerman found that coal tar was particularly useful in psoriasis therapy. Many observed that psoriasis improved with summer sun. In 1925, Goeckerman reported an additive benefit of coal tar and UVB radiation in psoriasis treatment. Goeckerman’s method remained the mainstay of psoriasis treatment for decades. In 1953, Ingram reported the successful treatment of psoriasis with a combination of Unna and Goeckerman’s modalities. He established the first day care center for psoriasis in which patients were treated with a tar bath, then UVB therapy, and lastly with 0.42% dithranol in Lassar’s paste. This treatment improved the morbidity of psoriasis for many patients, but was time intensive.
1950s – Corticosteroids
In the 1950s, the corticosteroid era began and revolutionized the treatment of many diseases. In 1950 Hench, Kendall, and Reichstein received the Nobel Prize for the development of cortisone. A mere 2 years later, Sulzberg and Witten reported that compound F, or hydrocortisone, was the first moderately successful topical corticosteroid in inflammatory skin diseases including psoriasis. From that time forward, additional topical corticosteroid preparations were developed to treat inflammatory dermatoses such as psoriasis.
1970s – Methotrexate and PUVA
Although methotrexate was first developed in the 1950s, it was not used to treat psoriasis until the 1970s. In 1946, Farber developed aminopterin to treat leukemia [40]. Five years later, Gubner reported that aminopterin used in the treatment of rheumatoid arthritis also cleared psoriasis. In 1958, Edmundsun and Guy introduced methotrexate, a more stable derivative of aminopterin with lower toxicity [41]. Investigators initially believed that folic acid antagonists prevented keratinocyte hyperproliferation, but later the effect on lymphocytes in psoriatic lesions was elucidated. In 1972, the FDA finally approved the use of methotrexate for psoriasis.
Also in the 1970s, PUVA therapy was reported to be effective in psoriasis. PUVA, based on the interaction between UV radiation and a photo-sensitizing chemical, has its own rich history. The concept originated in about 1'500 BC when Egyptian healers treated vitiligo with a combination of sunlight and ingestion of plants known as psoralens, including fig and limes. An article published in 1974 reported the efficacy of oral PUVA therapy in a group of patients with psoriasis. Three years later, a multi-center study confirmed that most patients with psoriasis experienced clearing of their skin using oralPUVA. Shortly after the development of oral PUVA, alternative bathwater delivery systems of psoralens were also created to minimize adverse effects associated with oral PUVA.
1980s – Narrowband UVB, retinoids, vitamin D
Although often therapeutically successful, PUVA therapy carries an increased risk of skin cancer. Therefore, further study of UVB therapy was undertaken. In 1981, Parrish and Jaenicke demonstrated that UVB wavelengths between 300 and 313 nm caused the greatest remission of skin lesions. Subsequent trials reported that the 311 nm spectrum showed improved clearance of lesions with less erythema.
In the 1980s, researchers also established the use of retinoids in psoriasis treatment. Prior to its use in psoriasis, in the 1960s physicians prescribed retinoids for hyperkeratosis and acne. At this time, first-generation and synthetic topical retinoids did not have significant antipsoriatic activity. In the early 1980s, reports demonstrated the efficacy of the second-generation retinoids etretinate and its derivative acitretin, in the treatment psoriasis. Although etretinate is no longer available in the US due to its lipophilia and protracted adverse effects, acitretin has a shorter half life and remains an important therapy in psoriasis. Third-generation acetylenic retinoids developed in the 1980s allowed for the production of a topical retinoid, tazarotene, with demonstrated anti-psoriatic efficacy.
The next class of drugs developed for psoriasis, vitamin D and its analogs, was also developed by chance observations in the 1980s. In 1985, a patient who received oral vitamin D3 for osteoporosis experienced dramatic improvement of his psoriasis. The active form of vitamin D3 plays a part in the control of intestinal calcium absorption, bone mineralization, keratinocyte differentiation, keratinocyte proliferation, and immune modulation. Despite extensive research, the exact mechanism of action of vitamin D analogs remains unknown. In 1988, a topical form of vitamin D proved useful in the treatment psoriasis.
1990s – Cyclic immunosuppressive medications
In 1997, cyclosporine was FDA approved for psoriasis treatment. Cyclosporine was isolated in 1969 from a fungus and was screened for antibiotic properties. In 1976, Borel reported immunosuppressive properties of cyclosporine in animal models. Three years later, Cyclosporine A was used experimentally in transplant patients to prevent graft rejection, and psoriatic patients in these trials experienced relief of their lesions. FDA approval was delayed until the 1990s due to concerns about toxicity. Cyclosporine is prescribed for severe psoriasis that is not responsive to other therapies.
Psoriasis Treatmen
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