Puva therapy

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Balneophotochemotherapy; Photochemotherapy

Definition
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Local or systemic application of methoxsalen (= psoralen; tricyclic furanocoumarin) for photosensitization with subsequent UVA irradiation. Methoxsalen (8-Methoxypsoralen; 8-MOP) or trimethylpsoralen (TMP) are mainly used. These are deposited in the cutaneous DNA and form non-covalent bonds (intercalation). By irradiation with long-wave UV light (UVA, 320-400 nm) at an action maximum at approx. 355 nm, the psoralens enter into a covalent bond with pyrimidine bases (especially thymine).

Effects
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  • Reduction of allergic late type reactions by reducing the number of Langerhans cells in the epidermis and thus reducing contact sensitization.
  • Reduction of keratinocyte proliferation.
  • Reduction of markers of epidermal activity such as keratin 16 or TGF-α.
  • Reduction of immunologically active proteins expressed by keratinocytes (HLA-DR, ICAM-1, IP-10), which are held responsible for the interaction with T-lymphocytes in psoriasis, for example.
  • Suppression of epidermal and dermal lymphocyte count and lymphocyte activity (CD3+, CD4+, CD8+, IL-2 receptor+), also in vivo.
  • Effect on cytokines (TGF-α, IL-2, IL-6, IL-8, TNF-α, IFN gamma) and on molecules which can directly promote hyperproliferation of the epidermis (e.g. EGF, IGF-1, IL1 receptors, see growth factors below).
  • Inhibition of DNA synthesis, increase in the rate of sister-chromatide exchange and increase in chromosome aberrations.

Indication
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Possible indications are:
  • alopecia areata
  • Eczema: Dermatitis, hypereosinophilic; eczema, atopic (except photoaggravated atopic eczema); eczema, contact allergic (hand and foot eczema); eczema, hyperkeratotic-rhagadiform hand and foot eczema.
  • Graft versus host disease (acute and chronic forms)
  • annular granuloma
  • lichen planus
  • Mycosis fungoides or cutaneous T-cell lymphoma in stages 1a, 1b and possibly 2a
  • Papulose, lymphomatoid
  • Pityriasis lichenoides (acute and chronic form), Pityriasis rubra pilaris
  • Photodermatoses (hardening with systemic PUVA therapy or PUVA bath therapy) e.g.: reticuloid, actinic; light reaction, persistent; light dermatosis, polymorphic; dermatitis, chronic actinic; light urticaria, Hidroa vacciniformia
  • protoporphyria, erythropoietic
  • Prurigo shapes
  • Psoriasis vulgaris, psoriasis (pustulosa) palmoplantaris
  • Scleroderma, circumscripts
  • Scleromyxoedema
  • urticaria pigmentosa
  • Vitiligo.

Implementation
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In general (according to E. Hölzle: Guidelines Phototherapy and Photochemotherapy):
  • First treatment dose 50-70% of the MPD or standard regimen according to skin type (see below the respective treatment types). Continuation of treatment 2-4 times/week.
  • No erythema and good response: increase the UVA dose by 30% twice a week.
  • Minimal erythema: no increase in UVA dose.
  • Persistent asymptomatic erythema: no increase.
  • Persistent symptomatic erythema (painful with or without edema or blistering): no further treatment until the symptoms subside.
  • Resumption of treatment: After the symptoms have subsided, reduction of the last dose by 50%, further increases of 10%.

Undesirable effects
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  • Acute 1st to 2nd degree burns with overdose, itching, nausea. If eye protection is missing, keratitis photoelectrica.
  • Chronic radiation damage to the skin: The most important long-term side effect of PUVA therapy is spinocellular carcinoma. After about 200-300 treatments, a significant increase in the skin tumour rate (primarily spinocellular carcinomas, hardly any basal cell carcinomas; no malignant melanomas!) by a factor of about 10-12 has been described. Further described are elastosis actinica; lentigines; melanoma, malignant, lentigo-maligna melanoma; basal cell carcinoma; testicular carcinoma in men (gonad protection!), questionable cataract formation (eye protection!).

Contraindication
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  • Increased risk of carcinoma: history of arsenic, pretreatment with ionising radiation, malignant skin tumours or dysplastic pigment moles, use of immunosuppressive drugs.
  • Increased photosensitivity: intake of photosensitizing drugs such as: tetracyclines, sulfonamides, diuretics. External use of photosensitizing substances such as tetracyclines, benzoyl peroxide, St. John's wort oil.
  • Photosensitive dermatoses: Herpes simplex infection, dermatomyositis, lupus erythematosus, photosensitive genodermatoses, photoaggravated endogenous eczema.
  • Especially in the case of oral PUVA treatment: severe liver and kidney damage (if necessary, consult an internist).
  • Especially during PUVA bath/shower treatment: cardiovascular problems, open wounds.
  • Other: Pregnancy, lactation, children under 12 years.

Note(s)
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  • The UVA initial dose depends on the individual sensitivity to the phototoxic reaction, which is defined by the minimum phototoxic dose ( MPD).
  • An increased risk of lymphoma in psoriatic patients after PUVA therapy does not seem to exist. On the other hand, the risk is increased in patients who simultaneously received a high cumulative dose of methotrexate.

Literature
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  1. Diederen PV et al (2003) Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: a retrospective study. J Am Acad Dermatol 48: 215-219
  2. Farr PM et al (1984) PUVA treatment of scleromyxoedema. Br J Dermatol 110: 347-350
  3. Friedmann PS (1981) Disappearance of epidermal Langerhans cells during PUVA therapy. Br J Dermatol 105: 219-221
  4. Girbig P et al (1988) Special late effects in PUVA patients. Act Dermatol 15: 28-31
  5. Hölzle E et al (2003) Recommendations for phototherapy and photochemotherapy. SDDG 1: 985-995
  6. Honigsmann H (2001) Phototherapy for psoriasis. Clin Exp Dermatol 26: 343-350
  7. Ibbotson SH et al (2001) The effect of methoxsalen dose on ultraviolet-A-induced erythema. J Invest Dermatol 116: 813-815
  8. Kwok YK et al (2002) Psoralen photochemotherapy (PUVA) is only moderately effective in widespread vitiligo: a 10-year retrospective study. Clin Exp Dermatol 27: 104-110
  9. Stern RS (2006) Lymphoma risk in psoriasis: results of the PUVA follow-up study. Arch Dermatol 142: 1132-1135
  10. Stern RS et al (1990) Genital tumors among men with psoriasis exposed to psoralens and ultraviolet A radiation (PUVA) and ultraviolet B radiation. N Engl J Med 322: 1093-1097
  11. Wolff K (1985) PUVA Pro and Contra. dermatologist 36: 25-33

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Last updated on: 29.10.2020