Psoralen and Ultraviolet A Therapy

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Psoralens form covalent linkages with pyrimidine bases in DNA when exposed to light of the appropriate wavelength, and if oxygen is present, reactive oxygen species also are generated. Although inhibition of DNA replication may account for some of the beneficial effects of PUVA therapy in certain hyperproliferative disorders such as psoriasis, PUVA has other important biological effects. It suppresses contact hypersensitivity and may evoke other immunological changes by affecting T lymphocytes and epidermal Langerhans cells. It increases melanin pigmentation in the skin and is useful in treating vitiligo. PUVA also inhibits mast cell release of inflammatory mediators.

Orally administered psoralens are rapidly absorbed (maximum photosensitivity for the most common preparation, 8-methoxypsoralen [Oxsoralen Ultra], is 1-1.5 hours). Although the elimination half-life is 2.2 hours, the skin remains photosensitive for 8 to 12 hours. Most excretion is renal, and the drug does not accumulate. It can be absorbed if applied topically, and after application to the entire body, therapeutic plasma levels can be detected.

PUVA is most useful for the treatment of severe psoriasis. Early (patch and plaque) stage cutaneous T-cell lymphoma (CTCL) also responds to PUVA therapy. In addition, patients in advanced stages of CTCL have been treated with a modification of PUVA known as extracorporeal photopheresis. In this therapy, blood from a CTCL patient who has taken psoralen is exposed to UVA light and returned to the patient. Lymphocytes are altered or destroyed by the treatment, and theoretically, the return of these abnormal cells triggers an immune response directed against certain lymphocyte surface antigens. The effectiveness of this modality appears to be variable.

Both topical and systemic PUVA are useful in some patients with vitiligo, although repigmentation is rarely complete. Other skin diseases for which PUVA may be helpful include atopic dermatitis, dyshidrotic eczema, and polymorphous light eruption.

Nausea is the most common acute side effect. About 36 to 48 hours after therapy, erythema and blistering can occur, especially if the UVA dose is too high or if the patient is exposed to other sources of UVA (such as sunlight). Long-term toxicities include the following:

• Squamous cell carcinoma of the skin (especially of the male genitalia). This risk is increased in patients already at risk because of fair skin, a history of skin cancer, and a history of exposure to other cutaneous carcinogens.

Melanoma. After 15 years or more of PUVA (>200 treatments) the risk of melanoma increases approximately fivefold in patients treated with higher doses in the United States.

Cataracts. Patients should wear UVA-absorb-ing wraparound sunglasses when exposed to ultraviolet light during the 24 hours after taking the drug.

Hyperpigmentation and development of discreet dark macules called PUVA lentigines.

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Natural Treatments For Psoriasis

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