Skin disease, psoralen

New impetus was given to photomedicine by development of lasers that are compatible with the clinical environment. These include HeNe, Ar ion, mby, and tunable dye lasers operating in the continuous wave (cw) mode. Prior to the advent of lasers in medicine, only the treatment of newborn jaundice, and the appHcation of long wavelength uv irradiation in conjunction with adininistration (or topical appHcation) of psoralen class sensitizers to treatment of skin diseases (86), principally psoriasis, were clinically important phototherapies. 

Psoralens, or furocoumarins, are a class of heterocyclic aromatic compounds used in photochemotherapy treatment of a variety of skin diseases such as psoriasis, vitiligo, mycosis fungoides, polymorphous light eruption, and more [68-71]. The compounds are present in numerous plants throughout the world. In photoche-... 

This work finally resulted in a new protocol for treating psoriasis, a chronic skin disease that can be seriously debilitating. The patient receives successive oral doses of methoxsalen followed by ultraviolet irradiation of the affected areas of skin. The procedure effectively controls psoriasis, and with improvements incorporated over the past twenty years it has become a standard therapy. Related procedures bring relief from several other skin diseases. In addition, the combination of psoralens and light has a key role in a promising treatment now under development for a white blood cell cancer. 

Recognition of the photosensitizing effect of the naturally occurring furanocoumarin psoralin (desmethoxy (3-6)) led to trials of its utility for the treatment of skin diseases such as psoriasis. The partial effectiveness of this compound led to the preparation of synthetic analogues. The two commercially available drugs, methoxsalen (3-8) and trioxsalen (4-6), are used in a procedure that goes by the acronym PUVA (psoralen and UVA irradiation) for the treatment of psoriasis and other skin diseases. 

Photochemotherapy, which consists of oral (and sometimes topical) administration of psoralens (the furo-coumarins 5-methoxypsoralen, 8-methoxypsoralen, and trioxysalen) plus long-wave ultraviolet radiation, known as PUVA, is a well-established effective treatment for psoriasis, which has also been used for vitiligo (1), mycosis fungoides, alopecia areata, dyshidrotic eczema, atopic dermatitis, and certain other skin diseases. Guidelines for treatment have been recommended (2,3). 

Photosensitizing dyes work through different mechanisms in the cell. For example, psoralens (Chapter 4.2.2) react under long-wavelength UV-irradiation with the thymine in DNA by cyclobutane addition forming mono- and diadducts. In this way the synthesis of nucleic acids is blocked. Pathological cell growth, as in the skin disease psoriasis, is thus prevented. 

Photosensitizers are agents that sensitize cells to radiation in the visible and near ultraviolet region of the radiation spectrum. Therapeutic use has been made of naturally occurring psoralens to treat vitiligo and psoriasis, in so-called photodynamic therapy. With newly developed UV irradiation systems that emit high-intensity UVA radiation, the principle has been extended to the treatment of severe psoriasis, mycosis fungoides and many other skin diseases. Agents used in psoralen photochemistry (PUVA) medicine include methoxypsoralen (8-MOP), trioxysalen and other synthetic psoralens. 

Nowadays, many human skin diseases, such as psoriasis, T-cell lymphoma (cutaneous T-cell lymphoma, CTCL mycosis fungoides MF), and vitiligo, are commonly treated with a combination of psoralens and UVA radiation commonly referred as PUVA (psoralens plus UVA) therapy. 

Oral administration of a psoralen such as methoxsalen (8-methoxypsoralen), followed by exposure to ultraviolet light (UV-A) can be used to treat psoriasis, eczema, vitiligo and a number of other skin diseases. There is a small risk of inducing relatively easily treatable, non-melanoma, skin cancers and possibly, generally only after extensive treatment, a very small risk of malignant melanoma. Similar psoralens are the components, somewhat controversially, of some tanning aids. 

Aside from their utility for the treatment of multiple skin manifestations, psoralens and UVA radiation could be used as a therapeutic alternative for several immune-mediated disorders as Crohn s disease and ulcerative colitis. Both are chronic inflammatory diseases of the gastrointestinal tract and are collectively known as inflammatory bowel disease. This disorder is produced by a dysfunction of the immtme system that leads to the accumulation of abtmdant lymphocytes and monocytes in the mucosa of the bowel, together with the secretion of cytokines and proinflammatory mediators. There are several genetic, environmental, and physiological factors that contribute to the pathogenesis of inflammatory bowel disease [151]. 

The main psoralen photosensitizing effect used in the treatment of certain skin diseases involves stimulating the pigmentation of melanocytes, increasing melanin synthesis on one hand and antiproliferative activity of psoriatic plaques on the other. The effects may, therefore, appear to be contradictory. However, recent findings explain that the two activities are likely to be connected to distinct cellular targets that are photomodified by psoralens in different ways. 

Vitiligo No safe and relfable treatment. Methoxsalen or other psoralen. Topically or syscemically, plus daily exposure to UVA (PUVA) is toxic, and ineffective in Caucasians. Sunscreens to protect the depigmented areas and reduce pigmentation of surrounding skin. Probably an autoimmune disease Note dose-dependent risk of squamous cell cancer with PUVA... 

PUVA is a psoralen+UV-A treatment for eczema, psoriasis, graft-versus-host disease, vitiligo, mycosis fungoides, large-plaque parapsoriasis and cutaneous T-cell lymphoma. The psoralen is applied or taken orally to sensitise the skin, and then the skin is exposed to UV A. The psoralens allow a relatively lower dose of UV A to be used. When they are combined with exposure to UV A in PUVA, they are highly effective at clearing psoriasis and vitiligo. 

Treatment of cutaneous T-cell lymphoma can be topical skin-directed or systemic. Topical options are used in the early skin-localized stage of the disease and include emollients, steroids, UVB radiation, retinoids, and PUVA. PUVA can produce relatively long-lived remissions. However, it is also associated with short-term side effects of oral psoralen intake, including nausea, vomiting, inconsistent gastrointestinal absorption, and long-term complications such as photosensitivity and the potential for development of skin cancer... 

An important apphcation of psoralens and UV-A light (PUVA therapy) was introduced into clinical practice by Parrish et al. A treatment consisting of the oral administration of 8-methoxypsoralen (8-MOP), followed by artificial ultraviolet illumination (UV-A) of patients skin was used for the first time to cure psoriasis, a disease characterized by hyperproliferation of skin cells. It is now recognized that psoriasis is an autoimmune disorder, and hyperproliferation is only one aspect of its manifestation. 

Besides their application in PUVA therapy to treat diseases characterized by hyperproliferation or the lack of pigmenting ability of some regions of the skin, in the last years, psoralens were also used in photopheresis, a therapeutic approach useful in treating immune disorders. 

---