Psoriasis PUVA therapy

In psoriasis, PUVA therapy (psoralen and UVA) leads to an inhibition of abnormally high rates of epidermal cell growth associated with the disease [297]. It has been shown that photoactivated psoralens are also potent inhibitors of epidermal cell growth in vitro. There are several lines of evidence that indicate the psoralen receptor is not associated with the DNA [298]. Studies on the distribution of compounds in cells based on their fluorescence properties demonstrated that psoralen (2) was present in the cytoplasm and cell surface membranes [299]. When cell membrane Auction of HeLa cells were prepared, psoralen receptor binding could be detected [297]. Using [3H]-8-MOP (methoxypsoralen), the cellular distribution of covalently bound psoralen in HeLa cells was also examined [300]. In these experiments, cells were treated with [3H]-8-MOP, then pulsed with UV light. It was indicated that labeled 8-MOP was distributed in cytoplasm and membrane finctions. These results have been repeated in several laboratories and all of them implicate targets outside of the nucleus... 

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. 

DNA (intercalation) (photosensitive yielding crosslinks) [dermatitic, mutagenic, phototoxic, PUVA therapy for leucoderma psoriasis]... 

PUVA is used most commonly in the treatment of psoriasis, vitiligo, and cutaneous T-cell lymphoma. However, up to 30 other skin diseases have been reported to be responsive to PUVA therapy. The most common of these include palmarplantar pustulosis, polymorphous light eruption, dishydrotic eczema, atopic dermatitis, allergic contact dermatitis, actinic reticuloid, solar urticaria, pityriasis lichenoides, and graft versus host disease. 

Candidates for PUVA therapy usually have moderate to severe, incapacitating psoriasis unresponsive to conventional topical and systemic therapies. A recent comparison of PUVA and NB-UVB involved 100 patients, 51 treated with NB-UVB and 49 receiving PUVA, with the results clearly favoring PUVA. Of these patients, 84% cleared with 16 PUVA treatments, whereas 63% cleared with 25 treatments of NB-UVB. °... 

Methoxsalen is supplied in soft gelatin capsules (Oxsoralen-Ultra) and hard gelatin capsules (8-MOP). The dose is 0.4 mg/kg for the soft capsule and 0.6 mg/kg for the hard capsule taken 1.5 to 2 hours before UVA exposure. A lotion containing 1% methoxsalen (Oxsoralen) also is available for topical application. It can be diluted for use in bath water to minimize systemic absorption. The risk of phototoxicity is increased with topical PUVA therapy. In U.S. and European multicenter cooperative studies of PUVA for the treatment of psoriasis, initial clearance rates approaching 90% were achieved. Relapse occurs within 6 months of cessation of treatment in many patients, which has prompted efforts to design maintenance protocols. 

Skin In a retrospective comparison of UVBTLOl phototherapy and PUVA therapy in patients with palmoplantar psoriasis, UVBTLOl was associated with adverse reactions in 20% of cases (erythema 18%, first-degree bums 7%) and treatment was discontinued in 4% PUVA therapy was associated with adverse reactions in 50% of patients and was mainly attributable to methoxypsoralen [63 ]. 

Redon E, Bursztejn A-C, Loos C, Barbaud A, Schmutz J-L. Etude retrospective de I efficacite et de la tolerance de la phototh6rapie UVBTLOl et de la PUVA th6rapie dans le psoriasis palmoplantaire. [A retrospective efficacy and safety study of UVB-TLOl phototherapy and PUVA therapy in palmoplantar psoriasis.] Ann Dermatol Venereol 2010 137(10) 597-603. 

PUVA is a treatment for eczema, psoriasis and vitiligo, which uses psoralen (furocoumarin molecule) as a photosensitiser, excited with UVA irradiation. The mechanism of PUVA action is similar to that of PDT, with photodynamic action utilising either a Type I or Type II mechanism. Psoralens are typically found in plants. They were known as early as ancient Egypt, but were only synthesised in a pure form in the 1970s. For PUVA therapy, psoralen can be taken orally or can be applied directly to the skin. PUVA therapy is highly effective at clearing skin problems such as psoriasis. 

Importantly, therapeutic efficacy of PUVA was drastically enhanced combining PUVA and oral administration of aromatic retinoid derivates such as etretinate 10 days before to starting PUVA therapy. This modality, called RePUVA, was able to reduce both the time and number of treatments necessary for complete clearance of psoriatic lesions (30%) and the UVA cumulative dose required to clear psoriasis (56%) [130,131]. Balneotherapy using 8-MOP and UVA radiation represents an alternative modality for the treatment of this skin disease [132]. 

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. 

Sequential therapy involves rapid clearing of psoriasis with aggressive therapy (e.g., cyclosporine), followed by a transitional period in which a safer drug such as acitretin is started at maximal dosing. Subsequently, a maintenance period using acitretin in lower doses or in combination with UVB or PUVA can be continued. 

Psoriasis Neoral and Gengraf are indicated for the treatment of adult, nonimmunocompromised patients with severe (ie, extensive and/or disabling), recalcitrant, plaque psoriasis who have failed to respond to at least 1 systemic therapy (eg, PUVA, retinoids, methotrexate) or in patients for whom other systemic therapies are contraindicated or cannot be tolerated. While rebound rarely occurs, most patients will experience relapse with Neoral or Gengraf as with other therapies upon cessation of treatment. 

Hypersensitivity to polyoxyethylated castor oil (injection only see Warnings and Administration and Dosage), cyclosporine, or any component of the products Gengraf and Neoral in psoriasis or RA patients with abnormal renal function, uncontrolled hypertension, or malignancies Gengraf and A/eora/concomitantly with PUVA or DVB, methotrexate or other immunosuppressive agents, coal tar or radiation therapy in psoriasis patients. 

Acitretin is most useful for the treatment of severe psoriasis, particularly the pustular and erythrodermic variants. Psoriatic nail changes and arthritis also may respond. Combining the drug with ultraviolet light therapy (Re-UVB, in the case of ultraviolet B radiation, or Re-PUVA, with psoralen plus ultraviolet A radiation) permits the use of lower doses of both acitretin and ultraviolet radiation. Other conditions for which the drug may be especially useful include congenital and acquired hyperkeratotic disorders, such as the ichthyoses and palmoplantar keratodermas, and severe lichen planus. 

For treating psoriasis, UVB phototherapy and PUVA are effective treatments that permit rapid control of the disease, but their side effects are similar to those of radiotherapy and chemotherapy. While these treatments can suppress the pathogenic change and rapidly improve the skin lesions, the heat penetrates into the blood, consumes the blood and Yin, and generates heat-toxin. Once the therapy is finished, the heat quickly arises and the skin lesions appear again, even worse than before the treatment, and the skin becomes more sensitive in general. In herbal treatment, one needs to reduce the heat-toxin, cool the blood, promote blood circulation and nourish the Yin. 

It is plain from this brief outline that treatment of psoriasis requires considerable judgement and choice will depend on the patient s sex, age and the severity of the condition. The combination of UVB and dithranol is probably the safest. When psoriasis is moderate-to-severe a strategy of rotation of treatments, e.g. UVB plus dithranol —> PUVA + acitretin —> UVB plus dithranol and so on may help to reduce the unwanted effects of any one therapy. 

In 1990, etretinate (Tigason) was replaced by acitretin (Neo-Tigason), an aromatic retinoid, a carboxylic acid metabolite of etretinate (15). It is effective in pustular psoriasis and psoriatic palmoplantar keratoderma and in combination with PUVA or topical therapy (calci-potriol or glucocorticoids) in the treatment of other forms of psoriasis. It has also been used to treat disorders of keratinization (ichthyosis, palmoplantar keratoderma, Darier s disease) and severe cutaneous forms of lichen planus. It prevents new skin carcinomas in patients with xeroderma pigmentosum and those who are immunosuppressed. The main advantage of acitretin is its short half-life of 50 hours, compared with over 80 days for etretinate (16). 

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