Psoriasis photochemotherapy

Multiple pharmacotherapeutic approaches to psoriasis management include first-line therapy for mild to moderate psoriasis with topical agents. In severe psoriasis, photochemotherapy and... 

Management of patients with psoriasis generally involves both nonpharmacologic and pharmacologic therapies. Pharmacologic alternatives for plaque psoriasis include topical treatments, phototherapy, photochemotherapy, and systemic therapies alone (orally or by injection). The choice of treatment is usually dictated by the severity of disease.15-17 In some cases, a combination of treatment options may be preferred. Topical therapies can be used in patients with limited or mild... 

Psoralen, or derivatives of 9-methoxy-7H-furo[3,2-g]chromen-7-one tricyclic ring structures, are used as photoreactive groups in crosslinkers, biotinylation compounds, and nucleic acid probes. Psoralens have been used for many years as photochemotherapy agents for treatment of psoriasis and vitiligo (Smith and Barker, 2006). Psoralens react when exposed to UV light... 

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-... 

Phototherapy is the generic term covering therapies which use light either with or without a sensitiser. Those that do not require a sensitiser use the natural chromophores within the tissue to perform this function e.g. treatment of vitamin D deficiency in rickets, and neonatal jaundice). Those that do use an added sensitiser include photochemotherapy (largely psoriasis and skin disorders) and photodynamic therapy (currently mainly cancer). Photodynamic therapy is differentiated from photochemotherapy by its additional requirement for the presence of oxygen at molecular or ambient levels.In this text we will deal only with photodynamic therapy since, at the present time, this is the main driving force in phototherapy. ° ... 

Trioxsalen and methoxsalen are psoralens used for the repigmentation of depigmented macules of vitiligo. With the recent development of high-intensity long-wave ultraviolet fluorescent lamps, photochemotherapy with oral methoxsalen for psoriasis and with oral trioxsalen for vitiligo has been under intensive investigation. 

A 55-year-old woman with psoriasis was treated with oral 5-methoxypsoralen and UVA photochemotherapy. After 40 treatments over 5 months she became unwell and complained of headaches, nausea, and abdominal pain. Laboratory tests confirmed a diagnosis of hepatitis. Six years earlier she had had flncloxacillin-indnced hepatitis. 

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). 

In a review of the English language literature on the risk of non-melanoma skin cancer from photochemotherapy in the treatment of psoriasis (34) the following were the conclusions ... 

Melski JW, Tanenbaum L, Parrish JA, Fitzpatrick TB, and Bleich HL (1977) Oral methoxsalen photochemotherapy for the treatment of psoriasis A cooperative clinical trial. Journal of Investigative Dermatology 68 328-335. 

Parrish JA, Fitzpatrick TB, Tanenbaum L, and Pathak MA (1974) Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. New England Journal of Medicine 291 1207-1211. 

A special class of DNA-dye complexes are the psoralen complexes (Chapter 6). They are used as drugs in the photochemotherapy of dermatosis such as psoriasis and vitiligo. Their biological action is attributed to their triplet states. Sloper et al. determined the quantum yield of the triplet formation by laser flash spectroscopy53). 

UVA combined with oral methoxsalen is a photochemotherapeu-tic approach to treatment of psoriasis. Although burdensome, photochemotherapy is an important treatment consideration for patients with moderate to severe psoriasis, when time needed to treat and risk factors are balanced with potential benefit. 

Systemic PUVA is approved for the treatment of psoriasis. It consists of oral ingestion of a potent photosensitizer such as methoxsalen (8-methoxypsoralen) at aconstant dose (0.6 to 0.8 mg/kg) and variable doses of UVA, depending on patient skin type and history of previous response to ultraviolet radiation (see Table 96-6 for skin type classifications ). Approximately 2 hours after ingesting psoralen, the patient is exposed to UVA light. Photochemotherapy is performed two or three times a week. In most patients, control and partial clearing occurs by the twenty-fifth treatment. 

Gordon PM, Diffey BL, Matthews JN, Farr PM. A randomized comparison of narrow-band TL-01 phototherapy and PUVA photochemotherapy for psoriasis. J Am Acad Dermatol 1999 41 728-732. 

In a clinical study, 15 patients (Group A) with chronic plaque psoriasis were treated with increasing concentrations (1-4%) of topical coal tar paste (Gilmour et al. 1993). These patients did not receive ultraviolet (UV) therapy and served as controls. Seventeen subjects (Group B) received UV-B phototherapy and four subjects (Group C) received psoralen photochemotherapy (PUVA). Another... 

The use of psoralens in the treatment of psoriasis and vitiligo has been discussed earlier. Psoriasis is a very common disease and photochemotherapy is a frequently used treatment (Tremblay and Bissonnette, 2002). Due to the carcinogenic effect of the PUVA treatment (Lindelof, 1999 Seidl et al., 2001), photosensitizers other than DNA intercalating psoralens are sought. It seems that PpIX induced by ALA may offer a good alternative (Bissonnette et al., 2002). 

Phototherapy is the use of ultraviolet light, which produces improvement in most patients with psoriasis but should only be done under supervision of a dermatologist. UVB is useful if patients have extensive small plaques of psoriasis resistant to topical treatment. Ultraviolet A (UVA) requires more specialized equipment and prior administration of an oral or topical photosensitizing drug called psoralen, in which case the treatment is known as photochemotherapy. 

Photochemotherapy with psoralen-containing plant extracts was employed for the treatment of vitiligo in Egypt and India as early as 1500 B.C. Orally administered 8-methoxypsoralen followed by UVA (PUVA) is FDA approved for the treatment of vitiligo, psoriasis, and cutaneous T-cell lymphoma. 

In one of India s sacred books Atharava-veda (1400 BC) it is described how seeds of the plant Psoralea corylifolia can be used for the treatment of vitiligo. Psoralens are the photoactive components of these seeds, just as in the extracts of the plant, Ammi majus, which grows on the banks of the Nile, was used by the Egyptians to treat vitiligo. For centuries photochemotherapy made no further progress until 1974 when PUVA (i.e. treatment with psoralens and UVA radiation) was reported to be an efficient treatment of psoriasis [13]. Photochemotherapy can also be tailored to act on the immune system such as in extracorporeal photophoresis of mucoses fungoides, cutaneous T-cell lymphoma [14]. 

J.A. Parrish, T.B. Fitzpatrick, L. Taneubaum, M.A. Pathac (1974). Photochemotherapy of psoriasis with oral methoxalen and longwave ultraviolet light. N. Engl. J. Med., 291, 1207-1211. 

Toxicological Implications for Man. Because psoralens are potent photoactive compounds, they have been used medically for treatment of skin de pigment at ion or vitiligo (16,17), and psoriasis (18). However, there has recently been concern associated with the medical use of these compounds (19). This concern is due to the observed phototoxicity during therapeutic use (17), the suspected photocarcinogenicity of xanthotoxin (20,21), and the latent onset of tumors in treated laboratory animals (22). Acute gout secondary to psoriasis also was exacerbated by psoralen and UV-A (PUVA) photochemotherapy (23). 

Activity Many F. induce a brown pigmentation in the skin on exposure to sunlight. They are photosensitizing, phototoxic, and can induce allergic dermatitis (Berloque s dermatitis), possibly with severe symptoms such as blister formation. The effect can also arise when, for example, scented toilet waters whose plant components still contain F. are applied to the skin. Use In photochemotherapy for vitiligo, psoriasis, atopic dermatitis, mycosis togoides. Photoactivated F. bind covalently as haptens to proteins as well as pyrimidines of DNA and thus have antimitotic effects. For synthesis, see Lit.. ... 

Melski JW, Tannenbaum L, Parrish JA et al. (1977) Oral methoxysalen photochemotherapy for the treatment of psoriasis. A cooperative clinical trial. J Invest Dermatol 68 328-335 Meltzer L, Baer RL (1949) Sensitization to monoglycerol paraaminobenzoate. J Invest Dermatol 12 31-38... 

Stem RS, Thibodeau LA, Kleinerman RA et al. (1979) Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis. N Engl J Med 300 809-813... 

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