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Advances in phototherapy
Dept. of Skin & STD, KMC, Mangalore - 575001
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Kumar P. Advances in phototherapy. Indian J Dermatol Venereol Leprol 2001;67:172-176
Phototherapy deals with the use of non-ionising electromagnetic radiation to bring about a beneficial effect on a particular disease. Photochemotherapy refers to a similar effect brought about by U V radiation when used in combination with chemicals like psoralens. Before the advent of modern scientific thought, sunlight was used for its beneficial effect by the ancient Indian and Egyptian civilizations thousands of years back., Niels Finsen first used UV light from a carbon arc lamp to treat lupus vulgaris in 1890 which heralded the era of modern phototherapy. El Mofty in 1948 and later Lerner et al studied the response of vitiligo to topical and oral psoralens., The term PUVA was coined for the use of psoralen and UVA in the treatment of psoriasis. In recent years the use of psoralen bath has become popular, bath PUVA originated in Scandinavia. During the past decade new devices and developments in phototherapy has opened new avenues for the treatment of photoresponsive dermatoses. The development of narrow band UVB and high dose UV-A1 has broadened the clinical spectrum of diseases that can be treated with phototherapy.
UVA ranges from 320 - 400nm and constitutes 90 -95 % of UVR reaching earth. They produce tanning of skin, erythema and burn which is maximum after 72 hrs. They penetrate beyond the dermis. It is least influenced by atmosphere and geographical factors UVA is carcinogenic and ages skin.
PUVA refers to the use of psoralens with UVA in photoresponsive dermatoses. The rationale of PUVA is to induce remissions of skin diseases by repeated controlled phototoxic reactions, when psoralens are activated by UVA. The exact nature of action of psoralens is not fully understood,, but they mainly produce their actions by two types of reactions. Type 1 is oxygen independent which results in formation of mono and bi functional adducts which inhibit DNA synthesis.,, The type 2 reaction is oxygen dependent resulting in oxidation of cellular contents leading to cell damage., Psoralens with UVA is also known to suppress abnormal immune response and kill inflammatory cells In vitiligo they stimulate melanogenesis by photoconjunction to DNA in melanocytes resulting in increased proliferation and distribution of the cells, they also stimulate production of larger melanosomes and transfer to keratinocytes Tyrosine synthesis is stimulated. Due to the harmful effects of UVA the following precautions have to be taken; UVA blocking glasses during and 24hrs after treatment, males are advised to take adequate measures to shield their genitalia as the scrotal skin being very thin can be prone to carcinomas.
Ultraviolet B rays constitute 5 - 10% of the UVR reaching earth. They range from 280 - 320nm. They penetrate the epidermis and are potent and harmful. UVB produces erythema and indirect tanning. It is influenced to a great extent by atmosphere and geographical factors.
Goeckerman and Ingrams regimen use the UVB component of UV light in treatment of psoriasis. UVB acts by damaging DNA, RNA and cell membrane by induction of photoproducts. With the development of UVB-narrow band fluorescent lamps by Philips (Philips TL-01) the prospects of better treatment for psoriasis has brightened., The TL-01 emits UV at 311 nm which matches the therapeutic optimum for faster clearance and longer remissions in psoriasis. The duration of treatment is reduced to 1/3 that of PUVA and broad band UVB. Comparative studies have demonstrated that NB 311 and PUVA are equally effective.,, Carcinogenic effect of UVB 311 is reduced significantly due to the decreased duration of treatment, it is cost effective compared to PUVA. Combinations include giving NB-UVB with dithranol, etretinate, tazarotene and PUVA. Retinoids have a beneficial effect on psoriasis and in addition have a anti carcinogenic property which further reduces the risk of UVB - induced skin malignancies.
High dose UVA-1 Phototherapy
Another advance in the field of phototherapy has been the use of high dose UVA-1 (340 - 400nm)., This can be used as a monotherapy in several inflammatory skin disorders. It is most useful in the treatment of atopic dermatitis. The dose given is as high as 130 J/cm daily for 15 consecutive days. The long term risks are yet to be evaluated, hence it is not recommended in persons below 18 years of age. Clinical scoring system and monitoring of eosinophilic cationic protein (ECP) was used in assessing its therapeutic efficacy., Urticaria pigmentosa and localized scleroderma are the other conditions in which high dose UVA-1 has been tried., High dose UVA-1 needs a special light source.
Photodynamic therapy (PDT) is the treatment of skin diseases by generating highly reactive oxygen intermediates by interaction of light with photosensitizers., PDT uses longer wave length light with deeper penetration to generate oxygen intermediates. The photosensitizing drugs used for dermatologic conditions are porphyrins, 5-aminolevulinic acid (ALA), benzo porphyrin derivatives. Free radicals produced cause cell damage. PDT is used for treating BCC, SCC, CTCL and, kaposis sarcoma. Among the non malignant conditions psoriasis, genital warts and actinic keratoses respond to PDT Preferential localization of the drug in tumour cells, because of its difference in vasculature makes it more useful in such diseases. PDT drugs are excited by UV light to triplet state. These excited drugs form free radicals (type 1 reactions) and transfer energy to molecular oxygen to form singlet oxygen (type 2 reactions).
It is used in advanced cases of CTCL and involves the ex vivo exposure of peripheral white blood cells to 8-MOP and UVA, which is followed by reinfusion to the circulation., Because of the decreased risk of side effects than that of conventional PUVA this treatment has been suggested in dermatological conditions like psoriasis, scleroderma, atopic dermatitis, pemphigus and SLE. However its practical use remains minimal.
Phototherapy in HIV infection
This is a controversial issue as both phototherapy and photochemotherapy can induce suppression of immunity which can lead to worsening of HIV status. Viral gene transcription and virus production could get a boost as the HIV promoter gets activated. It is also reported that HIV induced immune suppression could accelerate skin carcinomas due to UV radiation. On the other hand several reports point to the beneficial effects UVB and PUVA have on pruritus and psoriasis that manifest in HIV infection.,,, However long term observations are required to come to an appropriate conclusion The available data suggest that UVB is more likely to be harmful than PUVA in HIV infected persons., [Table - 1]
Protocol for PUVA
US Protocol: First exposure dose is given based on skin typing and is given 2-3 times per week. Increments range from 0.5 - 1.5J/cm2 depending on response.
European Protocol: Minimal phototoxicity dose (MPD) has to be determined before giving the first dose. Four treatments are given per week on 2 consecutive days followed by a rest day and then next 2 daily dose (11 0 11). Increments are given only after the first week and range from 0.5 - 2 J/ cm2.
Manipal Protocol: Studies done in Manipal have failed to demonstrate MPD in Indian skin. Srinivas et al have recommended a starting dose of 4 - 6J/cm2 with increments of 0.5J/cm2 depending on response. The maximum dose suggested is 18J/ cm2. Treatment is given 3 - 4 times per week.
Protocol for NB UVB 311
Determine the MED, initially give 70% of MED.
Subsequently if no erythema, increase by 20%. If there is minimal erythema maintain same dose. If there is well defined erythema postpone until next visit, give the same dose and later increase by only 10%. If there is painful erythema, edema or bullae withhold treatment until recovery then reduce exposure to half the starting dose and subsequently increase by 10% each visit., End point of treatment is clearance of the disease.
Several modes of delivery of psoralens are under research, it was found that sublingual delivery of psoralen in skin type 1 and 2 may be useful. It reduces the risk of hepatic and renal damage in patients who already have dysfunction of these two organs. Side effects like nausea and intolerance are also reduced.
Bath PUVA wherein a patient immerses himself in a solution of psoralen before UVA exposure has been popular for quite sometime now. It has been found that it is much safer and better than other modalities of UV treatment in psoriasis.,,
Photodynamic therapy discussed earlier for the treatment of skin tumours has been found to be useful in psoriasis.
Polyphenols present in green tea have a protective effect against skin damage caused by PUVA.
NB- 311 exposure given 4 times weekly for psoriasis has been found to be more risky in the development of long term side effects than 2 times weekly in Asian skin types 3 to 5. This study was done in Thailand and the dermatologists there do not recommend 4 per week schedule.
Oral khellin plus UVA (KUVA) is once again under scrutiny for treating vitiligo. Khellin which was used as a coronary vasodilator in the 1950s had caught the imagination of dermatologists for its pigmentary properties. Khellin is a furanochrome derived from the plant ammi visnaga. Given in a dose of 50 - 100mg, 2.5 hrs before UVA exposure, it produces significant repigmentation of vitiligo skin. It is less phototoxic and does not induce hyperpigmentation of non vitiliginous skin.
Segmental vitiligo is resistant to most forms of phototherapy but a new device BIOSKIN which can produce a focused beam of UVB has shown promise in microtherapy of segmental vitiligo.
Srinivas CR, Shenoi SD, Pai S. Psoralens. Indian J Dermatol Venereol Leprol 1997;63:276-287.[Google Scholar]
Fitzpatrick TB, Pathak MA. Historical aspects of methoxsalen and other furocoumarins.J Invest Dermatol 1959;23:229-231.[Google Scholar]
Van de Kerkhof PCM. Clinical features. In: Textbook of Psoriasis, 11 edn. Edited by Meir PD and Van de Kerkhof PCM, Churchhill Livingstone, Edinburgh, 1986; 13-39.[Google Scholar]
Marco Petrazzuoli. Advances in phototherapy. Curr Probl Dermatol, Nov/Dec 2000;282-286.[Google Scholar]
El Mofty AM. A preliminary clinical report on the treatment of leukoderma with Ammi majus Linn. J R Egypt Med Assoc 1948;31:651-655.[Google Scholar]
Lerner AB, Denton CR, Fitzpatrick TB. Clinical and experimental studies with 8-methoxy psoralen in vitiligo. J invest Dermatol 1953;20:299-314.[Google Scholar]
Parrish JA, Fitzpatrick TB, Taneubaum L, et al Photochemotherapy of psoriasis with oral methoxalen and long wave ultraviolet light. N Engl J Med 1974;291:1207-1211.[Google Scholar]
Fischer T, Alsins J. Treatment t of psoriasis with trioxalen baths and dysprosium lamps Acta Derm Venereol 1976;56:383-390.[Google Scholar]
Honigsmann H, Szeimies RM, Knobler R, et al. Photochemotherapy and Photodynamic Therapy, In: Dermatology in General Medicine, 5h Edn, Edited by Fitzpatrick et al, McGraw Hill Book Company, New York, 1999;2880-2900.[Google Scholar]
DallAcqua F. Principles of Psoralen photosensitization, In: The Fundamental Bases of Phototherapy, Edited by Honigsmann H et al, OEMF SpA, Milan, 1996, 1-16[Google Scholar]
Schmitt IM. Photobiology of psoralens, In: The Fundamental Bases of Phototherapy, Edited by Honigsmann H et al OEMF SpA, Milan, 1996,17-20.[Google Scholar]
Averbeck D. Recent advances in psoralen phototoxicity mechanism. Photochem Photobiol 1989;50:859-882.[Google Scholar]
Schmitt I, Chiment S, Gasperro FP. Psoralen protein photochemistry-the forgotten field. J Photochem Photobiol B: Biol 1995;27:101-107.[Google Scholar]
Imokawa G, Tejima T A possible role of prostaglandins in PUVA induced inflammation: Implication by organ cultured skin. J Invest Dermatol 1989;92:296-300.[Google Scholar]
Camp RDR. Psoriasis, In: Textbook of Dermatology, 6th Edn, Edited by Champion RH, Burton JL, Burns DA et al, Blackwell Science, London, 1998; 1589-1650.[Google Scholar]
Krutmann J. Therapeutic Photomedicine: Phototherapy, In: Dermatology in General Medicine,5th Edn, Edited by Fitzpatrick TB, Eizen KZ, Wolff K et al McGraw Hill Book Company, New York, 1999;2871-2879.[Google Scholar]
Van Weelden H, Baart de la Faille H, Young E, et al. Comparison of narrow band UVB phototherapy and PUVA photochemotherapy in the treatment of psoriasis. Acta Derm Venereol 1990;70:212-215.[Google Scholar]
Green CA, Lakshmipathi T, Johnson BE, et al. Comparison of the efficacy and relapse rates of narrow band UVB (TL01) monotherapy vs etretinate vs etretinate -PUVA in the treatment of psoriasis. Br J Dermatol 1992 ; 127 : 5 - 9.[Google Scholar]
Ortel B, Perl S, Kinaciyan T. Comparison of narrowband(311nm)UVB and broad band UVA after oral or bath-wash 8methoxypsoralen in the treatment of psoriasis. J Am Acad Dermatol 1993;29:736-740.[Google Scholar]
Krutmann J, Czech W, Diepgen T et al. High dose UVA-1 therapy in treatment of patients with atopic dermatitis. J Am Acad Dermatol 1992;26:225-230.[Google Scholar]
Costa C, Rilliet A, Nicolet M, et al. Scoring atopic dermatitis The simpler the better. Acta Derm Venereol 1989;69:41-45.[Google Scholar]
Czech W, Krutmann J, Schopf E, et al Serum eosinophilic cationic protein is a sensitive measure for disease activity in atopic dermatitis.Br J Dermatol 1992; 126:351-355.[Google Scholar]
Stege H. High dose UVA1 for urticaria pigmentosa Lancet 1996;347:64(Letter).[Google Scholar]
Stege H, Bernburg M, Humke S, et al. High dose UVA1 radiation therapy of localized sleroderma. J Am Acad Dermatol 1997;36:938+944.[Google Scholar]
Ullrich SE. Does exposure to UV radiation induce a shift to a Th2 like immune reaction? Photochem Photobiol 1996;64:254-258.[Google Scholar]
Morrey JD, Bourn SM, Bunch TD, et al. In vivo activation of human immunodeficiency virus typel long terminal repeat by UV type A light plus psoralen and UV-B light in the skin of transgenic mice. J Virol 1991;65:5045-5051.[Google Scholar]
Wang CY, Brodland DG, Su WP Skin cancers associated with acquired immunodeficiency syndrome. Mayo Clin Proc 1995;70:766772.[Google Scholar]
Meola T, Soter NA, Ostreicher R, et al. The safety of UVB phototherapy in patients with HIV infection. J Am Acad Dermatol 1993;29:216-220.[Google Scholar]
Lim HW, Vallurpalli S, Meola T, et al. UVB phototherapy is an effective treatment for pruritus in patients infected with HIV. J Am Acad Dermatol 1997;37:414-417.[Google Scholar]
Ranki A, Puska P, Mattinen S, et al. Effect of PUVA on immunologic and virologic findings in HIV infected patients. J Am Acad Dermatol 1991;24:404-410.[Google Scholar]
Horn TD, Morrison WL, Farzadegan H, et al. Effects of psoralen plus UVA radiation on HIV-1 in human beings: A pilot study. J Am Acad Dermatol 1994;31:735-740.[Google Scholar]
Zmudzka BZ, Miller SA, Jacobs ME et al. Medical UV exposures and HIV activation Photochem Photobiol 1996;64:246-253.[Google Scholar]
Morison WL. PUVA therapy is preferable to UVB phototherapy in the management of HIV associated dermatoses. Photoche Photobiol 1996;64:267-268.[Google Scholar]
Shepherd SE, Languth P, Panizzon RG. Pharmcokinetic behaviour of sublingually administered 8-methoxy psoralen for PUVA therapy. Photodermatol Photoimmunol Photomed 2001;17:11-21.[Google Scholar]
Karrer S, Eholzer C, Ackerman G, et al. Phototherapy of psoriasis: Comparative experience of different phototherapeutic approaches. Dermatology 2001;202:108-115.[Google Scholar]
Snellman E, Rantanen T, Sundell ].Cumulative UV radiation dose and outcome in clinical practice: effectiveness of trioxsalen bath PUVA with minimal UVA exposure. Photodermatol Photoimmunol Photomed 2000 ; 16 : 207 - 210.[Google Scholar]
Cooper EJ, Herd RM, Priestly GC, et al. A comparison of bath water and oral delivery of 8-methoxy psoralen in PUVA therapy for plaque psoriasis. Clin Exp Dermatol 2000 ; 25 : 111 - 114.[Google Scholar]
38.Boehncke WH, Elshorst-Schmit T, Kaufmann R. Systemic Photodynamic therapy is a safe and effective treatment for psoriasis. Arch Dermatol 2000 ; 136 : 271 - 272.[Google Scholar]
Zhao JF, Zhang YJ, Jin XH, et al. Green tea products protects against psoralen plus ultra violet A induced damage to skin. J Invest Dermatol 1999 ; 113 : 1070 - 1075.[Google Scholar]
Leenutaphong V, Nimkulrat P, Sudtim S. Comparison of phototherapy two times and four times a week with low doses of narrow band ultra violet B in Asian patients with psoriasis. Photodermatol Photoimmunol Photomed 2000; 16 : 202-206.[Google Scholar]
Goodwin RG, Finlay AY. Vitiligo following narrow band TL-01 phototherapy for psoriasis Br J Dermatol 2001;144 :1264-1266.[Google Scholar]
Scherschun L, Kim JJ, Lim HW. Narrow band ultra violet B is a useful and well tolerated treatment for vitiligo. J Am Acad Dermatol 2001;44 : 999-1003.[Google Scholar]
Hofer A, Kerl H Wolf P. Longterm results in the treatment of vitiligo with oral khellin plus UVA. Eur J Dermatol 2001; 11:225-229.[Google Scholar]
Lotti TM, Menchini G, Andreassi L. UVB radiation microphototherapy An elective treatment for segmental vitiligo. J Eur Acad Dermatol Venereol 1999; 13:102 -108.[Google Scholar]