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Psoralen plus ultraviolet A (PUVA) photochemotherapy

Elisabeth G Richard, MD
Section Editor
Craig A Elmets, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Psoralen plus ultraviolet A (PUVA) photochemotherapy combines the administration of psoralens, a class of phototoxic plant-derived compounds, with an exposure to ultraviolet A radiation (UVA). PUVA is used for the treatment of a variety of skin diseases, including psoriasis, mycosis fungoides, eczema, vitiligo, and graft-versus-host disease [1-3].

This topic will discuss the mechanism of action, treatment protocols, contraindications, adverse effects, and clinical indications of PUVA therapy. The use of PUVA for the treatment of specific skin conditions is discussed separately. UVB phototherapy and UVA1 phototherapy are discussed separately.

(See "Treatment of psoriasis in adults", section on 'Ultraviolet light'.)

(See "Treatment of early stage (IA to IIA) mycosis fungoides", section on 'PUVA'.)

(See "Management of severe refractory atopic dermatitis (eczema)", section on 'Psoralen plus UVA'.)

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Literature review current through: Oct 2017. | This topic last updated: May 10, 2017.
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  1. Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med 1974; 291:1207.
  2. Morison WL. Phototherapy and Photochemotherapy of Skin Disease, 3rd ed, Taylor and Francis, New York 2005.
  3. Abel EA. Photochemotherapy in Dermatology, Igaku-Shoin, New York 1992.
  4. Pathak MA, Fitzpatrick TB. The evolution of photochemotherapy with psoralens and UVA (PUVA): 2000 BC to 1992 AD. J Photochem Photobiol B 1992; 14:3.
  5. Brickl R, Schmid J, Koss FW. Clinical pharmacology of oral psoralen drugs. Photodermatol 1984; 1:174.
  6. Roelandts R, Van Boven M, Deheyn T, et al. Dietary influences on 8-MOP plasma levels in PUVA patients with psoriasis. Br J Dermatol 1981; 105:569.
  7. Herfst MJ, De Wolff FA. Intraindividual and interindividual variability in 8-methoxypsoralen kinetics and effect in psoriatic patients. Clin Pharmacol Ther 1983; 34:117.
  8. de Wolff FA, Thomas TV. Clinical pharmacokinetics of methoxsalen and other psoralens. Clin Pharmacokinet 1986; 11:62.
  9. Artuc M, Stuettgen G, Schalla W, et al. Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro. Br J Dermatol 1979; 101:669.
  10. Wulf HC, Andreasen MP. Distribution of 3H-8-MOP and its metabolites in rat organs after a single oral administration. J Invest Dermatol 1981; 76:252.
  11. Schmid J, Prox A, Reuter A, et al. The metabolism of 8-methoxypsoralen in man. Eur J Drug Metab Pharmacokinet 1980; 5:81.
  12. Honigsmann H, Szemies RM, Knobler R. Photochemotherapy and Photodynamic Therapy. In: Fitzpatrick's Dermatology in General Medicine, 8th Edition, Goldsmith LA, Katz SI, Gilchrest BA, et al. (Eds), McGraw Hill, New York 2012. Vol 2, p.2851.
  13. Viola G, Fortunato E, Cecconet L, et al. Central role of mitochondria and p53 in PUVA-induced apoptosis in human keratinocytes cell line NCTC-2544. Toxicol Appl Pharmacol 2008; 227:84.
  14. Farr PM, Diffey BL, Higgins EM, Matthews JN. The action spectrum between 320 and 400 nm for clearance of psoriasis by psoralen photochemotherapy. Br J Dermatol 1991; 124:443.
  15. Cripps DJ, Lowe NJ, Lerner AB. Action spectra of topical psoralens: a re-evaluation. Br J Dermatol 1982; 107:77.
  16. Parrish JA, White AD, Kingsbury T, et al. Photochemotherapy of psoriasis using methoxsalen and sunlight. A controlled study. Arch Dermatol 1977; 113:1529.
  17. Buerger C, Malisiewicz B, Eiser A, et al. Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin. Br J Dermatol 2013; 169:156.
  18. Shirsath N, Mayer G, Singh TP, Wolf P. 8-methoxypsoralen plus UVA (PUVA) therapy normalizes signalling of phosphorylated component of mTOR pathway in psoriatic skin of K5.hTGFβ1 transgenic mice. Exp Dermatol 2015; 24:889.
  19. Sethi G, Sodhi A. Role of p38 mitogen-activated protein kinase and caspases in UV-B-induced apoptosis of murine peritoneal macrophages. Photochem Photobiol 2004; 79:48.
  20. Laing TJ, Richardson BC, Toth MB, et al. Ultraviolet light and 8-methoxypsoralen inhibit expression of endothelial adhesion molecules. J Rheumatol 1995; 22:2126.
  21. Singh TP, Schön MP, Wallbrecht K, et al. 8-methoxypsoralen plus ultraviolet A therapy acts via inhibition of the IL-23/Th17 axis and induction of Foxp3+ regulatory T cells involving CTLA4 signaling in a psoriasis-like skin disorder. J Immunol 2010; 184:7257.
  22. Johnson R, Staiano-Coico L, Austin L, et al. PUVA treatment selectively induces a cell cycle block and subsequent apoptosis in human T-lymphocytes. Photochem Photobiol 1996; 63:566.
  23. Liszewski W, Naym DG, Biskup E, Gniadecki R. Psoralen with ultraviolet A-induced apoptosis of cutaneous lymphoma cell lines is augmented by type I interferons via the JAK1-STAT1 pathway. Photodermatol Photoimmunol Photomed 2017; 33:164.
  24. Mengeaud V, Ortonne JP. PUVA (5-methoxypsoralen plus UVA) enhances melanogenesis and modulates expression of melanogenic proteins in cultured melanocytes. J Invest Dermatol 1996; 107:57.
  25. Ibbotson SH, Farr PM. The time-course of psoralen ultraviolet A (PUVA) erythema. J Invest Dermatol 1999; 113:346.
  26. Buckley DA, Phillips WG. 8-Methoxypsoralen PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen with a skin-type approach. Br J Dermatol 1997; 136:800.
  27. Collins P, Wainwright NJ, Amorim I, et al. 8-MOP PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen with a skin-type approach. Br J Dermatol 1996; 135:248.
  28. Stern RS, Fitzpatrick TB, Honigsmann H, et al. Psoralen photochemotherapy. In: Psoriasis, Roenigk HH, Maibach HI (Eds), Marcel Dekker, New York 1985. p.475.
  29. Photochemotherapy for psoriasis. A clinical cooperative study of PUVA-48 and PUVA-64. Arch Dermatol 1979; 115:576.
  30. Henseler T, Wolff K, Hönigsmann H, Christophers E. Oral 8-methoxypsoralen photochemotherapy of psoriasis. The European PUVA study: a cooperative study among 18 European centres. Lancet 1981; 1:853.
  31. Wolff KW, Fitzpatrick TB, Parrish JA, et al. Photochemotherapy for psoriasis with orally administered methoxsalen. Arch Dermatol 1976; 112:943.
  32. Melski JW, Tanenbaum L, Parrish JA, et al. Oral methoxsalen photochemotherapy for the treatment of psoriasis: a cooperative clinical trial. J Invest Dermatol 1977; 68:328.
  33. Gange RW, Levins P, Murray J, et al. Prolonged skin photosensitization induced by methoxsalen and subphototoxic UVA irradiation. J Invest Dermatol 1984; 82:219.
  34. Halpern SM, Anstey AV, Dawe RS, et al. Guidelines for topical PUVA: a report of a workshop of the British photodermatology group. Br J Dermatol 2000; 142:22.
  35. Kappes UP, Barta U, Merkel U, et al. High plasma levels of 8-methoxypsoralen following bath water delivery in dermatological patients. Skin Pharmacol Appl Skin Physiol 2003; 16:305.
  36. Morison WL, Marwaha S, Beck L. PUVA-induced phototoxicity: incidence and causes. J Am Acad Dermatol 1997; 36:183.
  37. Zamiri M, Bilsland D. Treatment of bath PUVA-induced skin pain with gabapentin. Br J Dermatol 2004; 151:516.
  38. Tegner E. Severe skin pain after PUVA treatment. Acta Derm Venereol 1979; 59:467.
  39. Tegner E. Excruciating skin pain after PUVA treatment. Int J Dermatol 1982; 21:207.
  40. Kumakiri M, Hashimoto K, Willis I. Biological changes of human cutaneous nerves caused by ultraviolet irradiation: an ultrastructural study. Br J Dermatol 1978; 99:65.
  41. Prens EP, Smeenk G. Effect of photochemotherapy on the cardiovascular system. Dermatologica 1983; 167:208.
  42. Mackie RM. Onycholysis occurring during PUVA therapy. Clin Exp Dermatol 1979; 4:111.
  43. Ledbetter LS, Hsu S. Melanonychia associated with PUVA therapy. J Am Acad Dermatol 2003; 48:S31.
  44. Rampen FH. Hypertrichosis in PUVA-treated patients. Br J Dermatol 1983; 109:657.
  45. Gschnait F, Wolff K, Hönigsmann H, et al. Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients. Br J Dermatol 1980; 103:11.
  46. Rhodes AR, Harrist TJ, Momtaz-T K. The PUVA-induced pigmented macule: a lentiginous proliferation of large, sometimes cytologically atypical, melanocytes. J Am Acad Dermatol 1983; 9:47.
  47. Stern RS. Actinic degeneration and pigmentary change in association with psoralen and UVA treatment: a 20-year prospective study. J Am Acad Dermatol 2003; 48:61.
  48. Lindelöf B, Sigurgeirsson B, Tegner E, et al. PUVA and cancer: a large-scale epidemiological study. Lancet 1991; 338:91.
  49. Stern RS, Lunder EJ. Risk of squamous cell carcinoma and methoxsalen (psoralen) and UV-A radiation (PUVA). A meta-analysis. Arch Dermatol 1998; 134:1582.
  50. Stern RS, PUVA Follow-Up Study. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Am Acad Dermatol 2012; 66:553.
  51. Marcil I, Stern RS. Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study. Lancet 2001; 358:1042.
  52. Stern RS, Bagheri S, Nichols K, PUVA Follow Up Study. The persistent risk of genital tumors among men treated with psoralen plus ultraviolet A (PUVA) for psoriasis. J Am Acad Dermatol 2002; 47:33.
  53. Stern RS, Nichols KT, Väkevä LH. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study. N Engl J Med 1997; 336:1041.
  54. Morison WL, Baughman RD, Day RM, et al. Consensus workshop on the toxic effects of long-term PUVA therapy. Arch Dermatol 1998; 134:595.
  55. Malanos D, Stern RS. Psoralen plus ultraviolet A does not increase the risk of cataracts: a 25-year prospective study. J Am Acad Dermatol 2007; 57:231.
  56. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol 2010; 62:114.
  57. Morison WL, Richard EG. PUVA photochemotherapy and other phototherapy modalities. In: Comprehensive dermatologic drug therapy, 3rd ed, Wolverton SE (Ed), Saunders Elsevier, Philadelphia 2013.