HISTORY

The history of phototherapy: Something new under the sun?

Rik Roelandts, MD, PhD Leuven, Belgium
Phototherapy has a very long, albeit mostly anecdotal history. Real interest in the use of ultraviolet irradiation in the treatment of various diseases started in the 19th century and reached a climax when Niels Finsen received the Nobel Prize in 1903 for his therapeutic results with lupus vulgaris. This marked the start of modern phototherapy. It was used in thermal stations for treatment of tuberculosis, in the treatment of leg ulcers in wartime, and in the treatment of skin diseases. This article reviews the history of a treatment modality that greatly changed modern dermatologic treatment, although it is as old as mankind. (J Am Acad Dermatol 2002;46:926-30.)

FROM HELIOTHERAPY TO PHOTOTHERAPY

Probably the rst report of the therapeutic use of sunlight for medical purposes (heliotherapy) dates from about 1400 BC and deals with the treatment of skin diseases. Hindus with vitiligo were given certain plant extracts and then exposed to the sun.1 Over the centuries, sunlight has been used in the treatment of many diseases in different countries, such as ancient Egypt, Greece, and Rome; but the records are mostly anecdotal. Many believed that the therapeutic effect was due to the red light and the heat of the sun. At that time, there was no notion of ultraviolet (UV) rays, which were not discovered until 1801.2 In the second half of the 19th century, more and more people became interested in heliotherapy. In 1855, Rikli from Switzerland opened a thermal station in Veldes in Slovenia for the provision of heliotherapy.3 In 1856, Florence Nightingale in the United Kingdom protested against the orientation of the Royal Victoria Hospital in Netley near Southampton,4 observing that no sunlight could enter its wards. In 1877, Downes and Blunt showed that sunlight could kill anthrax bacilli.5 In 1890, Palm from Edinburgh suggested that the sun could play a

From the Department of Dermatology, Photodermatology Unit, University Hospital, Leuven. Funding sources: None. Conict of interest: None. Reprint requests: Rik Roelandts, MD, PhD, the Department of Dermatology, Photodermatology Unit, University Hospital, Kapucijnenvoer 33, 3000 Leuven, Belgium. Copyright 2002 by the American Academy of Dermatology, Inc. 0190-9622/2002/$35.00 0 16/1/121354 doi:10.1067/mjd.2002.121354

therapeutic role in rachitis,6 but he was ignored in his own city and everywhere else. When in 1901, the rst beds in any hospital in the world assigned to pregnant women were inaugurated in the Royal Maternity Hospital in Edinburgh, the rst patient ironically enough turned out to be a woman with rickets from Leeds.5 Both the patient and her child died. It was only in 1919, 29 years after Palms ndings, that phototherapy became established in the treatment of rickets as a result of the efforts of Huldschinsky in Berlin and Hess in New York. In the same year, 1890, when Palm published his experiences with rickets, Konig gave a talk in Berlin about his therapeutic results with sun exposure for peritoneal tuberculosis. He would open the body to expose the peritoneum and in this way healed 107 of a series of 131 patients.7 Today, this might seem to be a heroic procedure, but at the time, when tuberculosis was one of the most common causes of death, every type of treatment was welcome. At the end of the 19th century, many people had begun to realize that the UV rays of the sun were the most important wavelengths for its therapeutic effects. This was a big step forward and resulted in the use of ltered solar radiation and articial light sources. In 1893, Finsen in Denmark used ltered sunlight in the treatment of lupus vulgaris.5 A year later, in 1894, Lahmann in Germany was probably the rst to construct and use articial light sources in the treatment of skin diseases (phototherapy). He used a carbon arc lamp in combination with a parabolic mirror and was able to heal a patient with lupus vulgaris of the nose and had improvement in another patient with the same condition.3 Phototherapy had become an alternative for heliotherapy. The rst book on phototherapy is probably Die Heilkraft des Lichtes by Willibald Gebhardt, which

926

J AM ACAD DERMATOL VOLUME 46, NUMBER 6

Roelandts 927

was published in 1898.8 In this book, Gebhardt describes the indications, methods, and equipment for phototherapy. The most important indications at that time were lupus vulgaris, acne, psoriasis, prurigo, syphilis, leprosy, and pellagra. The main problem was still the low output of the lamps. In 1901, Finsen published the results of treatment of lupus vulgaris with concentrated doses of UV radiation from a carbon arc lamp. For this, he received the Nobel Prize in Medicine in 1903, and he is the only dermatologist ever to be awarded one. Between November 1895 and March 1903, more than 950 cases of lupus vulgaris were treated in Finsens Lysinstitut.9 Finsen also wrote the foreword to the rst French textbook on phototherapy, which was published in 1903.10 In 1906, Kuch in Hanau, Germany, made the rst quartz lamp. This lamp was introduced to medicine by Nagelschmidt in 1911. In 1912 when Kromayer made a quartz lamp with a high UV output, it became possible to treat different skin diseases.11

trated by the opinion of a medical ofcer of health and professor of public health of an English university, which appeared in the Manchester Guardian of April 24, 1922: No one who has the true interests of our tuberculous population at heart can fail to regret Dr Saleebys suggestion that sunshine can cure tuberculosis. In 1923, Rolliers book was translated into English and published under the title Heliotherapy.12 The use of sun exposure in the treatment of tuberculosis became increasingly popular. Only when the rst tuberculostatic agents became available in 1946 did the use of sun exposure to treat tuberculosis become less popular, until it was nally relegated to history.

THE USE OF HELIOTHERAPY AND PHOTOTHERAPY IN THE TREATMENT OF LEG ULCERS

The rst to report a therapeutic effect of sun exposure in the treatment of ulcers was Larrey, Napoleons private physician. He noted, during Napoleons campaign in Egypt from 1798 to 1799, that the soldiers traumatic ulcers healed more quickly after sun exposure.13 In 1904, Bernhard in Switzerland described heliotherapy as a treatment for skin ulcers.14 One year later, in 1905, Casanouve-Soule in France published a thesis on the use of phototherapy for atonic ulcers. The results appeared to be very mediocre. However, as a result of the inuence of other authors,15-17 the treatment of wounds with sunlight gradually gained ground, especially in Switzerland, Germany, and France. During the First World War from 1914 to 1918, ulcers were treated by exposure to natural sunlight or to quartz lamps. This was done in Germany, the United Kingdom, France, and Italy. The German military authorities even started several special departments for radiation treatment.18 In the United Kingdom, a similar treatment center was set up in Maidenhead on the property of the Astor family (Hever Castle). The French and the Italians treated their war patients on the sunny coasts of the Mediterranean.13 Even the German Navy used the sun in the treatment of wounds.19 During the Second World War from 1940 to 1945, this open-air treatment with sunlight or quartz lamps was still being used. When the rst antibiotics became available, however, interest in using phototherapy for wound healing faded until recently, when low-level laser therapy was suggested for the treatment of venous leg ulcers20,21 and radiotherapyinduced ulcers.22 The role of heliotherapy in the treatment of leg ulcers has been explained by different mechanisms

THE USE OF HELIOTHERAPY IN THERMAL STATIONS

One of the rst applications of an organized use of sun exposure in medicine was in the treatment of tuberculosis in thermal stations. In 1903, in Leysin, Switzerland, Rollier opened the rst hospital to treat tuberculosis and rachitis with sun exposure. He used a treatment schedule in which patients feet were exposed 2 to 3 times for 5 minutes on the rst day and 2 to 3 times for 10 minutes on the second day. On the second day, the legs were also exposed 2 to 3 times for 5 minutes. In this way, he increased the exposure times, as well as the amount of body area exposed, until after 14 days, the entire body was exposed for 3 to 6 hours a day.5 In 1914, Rollier published his therapeutic results in a book, La Cure du Soleil, which, unfortunately, was published in French at the start of the First World War. That his book had no great effect outside Switzerland is illustrated by the fact that there was not one talk about the use of UV radiation during The International Conference against Tuberculosis in London in 1921. It was not until 1922 that the United Kingdom became really interested in the use and study of sunlight in medicine, mainly as a result of the work of Saleeby, who had become a keen promoter of heliotherapy and phototherapy after visiting Rolliers treatment center in Switzerland. The Medical Research Council appointed a Committee on Sunlight with Sir William Bayliss as the chairman.5 In the same year, a light department was opened at the London Hospital. It was a hard ght, which is illus-

928 Roelandts

J AM ACAD DERMATOL JUNE 2002

such as an antiseptic action, a stimulation of epithelial cells, an analgetic action, and an improvement of the local circulation caused by the hyperemia.

THE USE OF PHOTOTHERAPY FOR SKIN DISEASES

The use of articial lamps gradually changed the use of UV irradiation in medicine. Although heliotherapy with natural sunlight was mainly used in thermal stations to treat tuberculosis and in wartime to treat leg ulcers, phototherapy was and is now mainly used in dermatology to treat skin disorders. The rst report of the use of phototherapy in the treatment of skin disorders dates from about 1400 BC among Hindus, as already mentioned. They used photochemotherapyadministration of plant extracts, followed by sun exposurefor vitiligo.1 The same treatment was also used in ancient Egypt. The active ingredients in these plant extracts were isolated in 1947 by Fahmy et al23-25 as 8methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP). In the same year, these authors and also El Mofty started to treat patients with vitiligo with 8-MOP and sun exposure.26 In 1960, Buck et al27 in the United Kingdom and Pathak and Fellman28 in the United States determined the action spectrum of 8-MOP in the UVA range. The rst to report the use of 8-MOP in combination with UV irradiation in the treatment of psoriasis were Allyn29 in 1962 who used topical 8-MOP and Oddoze et al30 in 1967 who used oral 8-MOP. In 1969 Fulton et al31 used black light UVA tubes for the rst time in combination with topical 8-MOP in the treatment of vitiligo. A year later, in 1970, Mortazawi32 and Mortazawi and Oberste-Lehn33 used the same type of UVA tubes in a total-body-irradiation cabin with topical 8-MOP for the treatment of psoriasis. The use of total-body irradiation was not new. Already at the beginning of the 1960s, Wiskemann34 in Hamburg, Germany, had constructed one phototherapy system with Osram Ultravitalux lamps and another with uorescent UVB tubes. In 1963, Forck35 in Munster, Germany, constructed a totalbody irradiation source with 8 Hanau lamps to treat psoriasis and mycosis fungoides. However, the use of UVA tubes in a total-body-irradiation cabin was new. The UVA output of these tubes was effective when the 8-MOP was used topically but was insufcient when it was administered orally. In 1974, Parrish et al36 reported the use of a new type of a high-intensity UVA tube in combination with oral 8-MOP in the treatment of psoriasis, which was much more effective. This was the start of pso-

ralen UVA range (PUVA) treatment. The term photochemotherapy was rst used by Fitzpatrick that same year after he wrote it on a napkin.37 Soon afterward, a cooperative clinical trial was started.38 It turned out to be one of the rst and largest prospective follow-up studies of a new medical technology.37 In 1979, Honigsmann et al39 described the use of oral 5-MOP as an alternative to 8-MOP. It was a very long way from the use of plant extracts and sun exposure to treat vitiligo to the use of oral 8-MOP and total-body-UVA-irradiation cabins to treat psoriasis. So many steps had to be taken in so many different countries throughout history that one might well wonder how it ever could have happened. Many people were involved. As is often the case in history, some had bright ideas, and others put them into practice. The history of UVB phototherapy is not as old as the history of photochemotherapy. Real interest started with the work of Finsen in the treatment of lupus vulgaris. In 1923, Alderson recommended using a mercury quartz lamp to treat psoriasis.40 In 1925, Goeckerman41 combined tar with UV irradiation for the treatment of psoriasis. For about half a century, this remained the most popular form of phototherapy in dermatology. The main drawback of this combination was the low output of the lamps. This changed in 1978 when Wiskemann42 suggested an irradiation cabin with broadband UVB tubes for the treatment of psoriasis. During the subsequent years, broadband UVB phototherapy became an alternative for photochemotherapy in the treatment of psoriasis and the therapy of choice for the treatment of therapy-resistant uremic pruritus and other types of pruritus. However, broadband UVB phototherapy was less efcient for treating psoriasis than PUVA and so never achieved popularity. The breakthrough came after 1988 when the more efcient narrowband UVB phototherapy was introduced for the treatment of psoriasis by van Weelden et al43 and by Green et al.44 In the meantime, other types of phototherapy have been developed, such as extracorporeal photopheresis for cutaneous T-cell lymphoma by Edelson et al45 in 1987 and high-dose-UVA1 phototherapy for atopic dermatitis by Krutmann and Schopf46 in 1992. In that same year, topical photodynamic therapy with visible light was introduced in dermatology by Kennedy and Pottier47 for the treatment of supercial basal cell carcinoma. Over the years, a number of books on phototherapy of skin diseases have been published.48-52 Although phototherapy is now mostly used in dermatology, treatment of skin diseases is not its only indication. Since a nursing sister in 1958 accidentally

J AM ACAD DERMATOL VOLUME 46, NUMBER 6

Roelandts 929

noticed that the skin of a jaundiced baby had faded after exposure to sunlight, phototherapy has also been used to treat neonatal hyperbilirubinemia.53 Another indication, since 1982, is the use of phototherapy for seasonal affective disorder.54,55 In both cases, visible light is used and not UV radiation. The developments in irradiation techniques and equipment and new indications for its use in recent years have kept phototherapy from becoming obsolete, even though it is at least as old as recorded history.

22.

23.

24. 25.

REFERENCES 1. Fitzpatrick TB, Pathak MA. Historical aspects of methoxsalen and other furocoumarins. J Invest Dermatol 1959;31:229-31. 2. Ritter JW. Bemerkungen zu Herschels neueren Untersuchungen uber das Licht. In: Physisch-Chemische Abhandlungen, in chronologischen Folge. II Band. Leipzig: Reclam; 1806. p. 81-107. 3. Barth J, Kohler U. Photodermatologie in Dresden-ein histo rischer Abriss. Festschrift anlasslich des 75. Geburtstages von Prof. Dr. Dr. Dr. h.c. H.-E. Kleine-Natrop (1917-1985). Dresden: 1992. 4. From a special correspondent. Royal Victoria Hospital, Netley. Br Med J 1966;5484:412-3. 5. Saleeby CW. Sunlight and health. 3rd ed. London: Nisbet & Co; 1923-1926. 6. Palm TA. The geographical distribution and aetiology of rickets. The Practitioner Oct/Nov 1890. 7. Ziegelroth. Die elektrische Belichtung bei Lupus. Blatter fur kli nische Hydrotherapie. 1895;Juni:138-40. 8. Meffert H, Bahr T. Willibald Gebhardt (1861-1921). Sein Leben und seine Verdienste um die Photomedizin. Dermatol Monatsschr 1989;175:699-705. 9. Montgomery FH. The present status of phototherapy. J Cutan Dis 1903;21:529-48. 10. Leredde P. Phototherapie et photobiologie. Paris: Naud; 1903. 11. Schafer V. Articial production of ultraviolet radiation, intro duction and historical review. In: Urbach F, editor. The biologic effects of ultraviolet radiation. Oxford: Pergamon; 1969. p. 93-105. 12. Rollier A. Heliotherapy. Oxford: Oxford Medical Publications; 1923. 13. Bernhard O. Light treatment in surgery. London: Edward Arnold & Co; 1926. 14. Bernhard O. Uber offene Wundbehandlung durch Insolation und Eintrocknung. Munch Med Wochenschr 1904;1. 15. Haeberlin. Zur Behandlung granulierender Wunden. Munch Med Wochenschr 1907;8. 16. Dosquet W. Offene Wundbehandlung und Freiluftbehandlung. Leipzig: Georg Thieme; 1916. 17. Backer. Sonnen und Freiluftbehandlung schwer eiternder Wunden. Ebenda 1914;52. 18. Kriegstatigkeit des Badischen Frauenvereins 1914-1919. Karlsruhe, Germany: F.C. Mullersche Hofbuchdruckerei; 1919. p. 37-8. 19. Asbeck. Ueber Sonnenlichtbehandlung. MMW Munch Med Wochenschr 1917;2. Feldarztliche Beilage Nr 2:65. 20. Sugrue ME, Carolan J, Leen EJ, Feeley TM, Moore DJ, Shanik GD. The use of infrared laser therapy in the treatment of venous ulceration. Ann Vasc Surg 1990;4:179-81. 21. Cullum N, Nelson EA, Flemming K, Sheldon T. Systematic reviews of wound care management: (5) beds; (6) compression; (7)

26. 27.

28. 29.

30.

31. 32.

33. 34. 35. 36.

37.

38.

39.

40. 41. 42. 43.

44.

laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy. Health Technol Assess 2001;5:1-221. Schindl A, Schindl M, Pernerstorfer-Schon H, Mossbacher U, Schindl L. Low intensity laser irradiation in the treatment of recalcitrant radiation ulcers in patients with breast cancer longterm results of 3 cases. Photodermatol Photoimmunol Photomed 2000;16:34-7. Fahmy IR, Abu-Shady H. Ammi majus Linn: pharmacognostical study and isolation of a crystalline constituent, ammoidin. Q J Pharmacol 1947;20:281-91. Fahmy IR, Abu-Shady H, Schonberg A, Sina A. A crystalline prin ciple from Ammi majus L. Nature 1947;160:468-9. Fahmy IR, Abu-Shady H. Ammi majus Linn: the isolation and properties of ammoidin, ammidin and majudin, and their effect in the treatment of leukoderma. Q J Pharmacol 1948;21:499503. Roelandts R. The history of photochemotherapy. Photodermatol Photoimmunol Photomed 1991;8:184-9. Buck HW, Magnus IA, Porter AD. The action spectrum of 8methoxypsoralen for erythema in human skin. Br J Dermatol 1960;72:249-55. Pathak MA, Fellman JH. Activating and uorescent wavelengths of furocoumarins: psoralens. Nature 1960;185:382-3. Allyn B. Studies on phototoxicity in man and laboratory animals. Presented at the Twenty-First Annual Meeting of the American Academy of Dermatology; 1962 Dec; Chicago. Oddoze L, Temime P, Marchand JP, Benne M. Lassociation meladinine per os et rayons U.V. dans le traitement du psoriasis. Bull Soc Fr Dermatol Syph 1967;74:609-10. Fulton JE, Leyden J, Papa C. Treatment of vitiligo with topical methoxsalen and blacklite. Arch Dermatol 1969;100:224-9. Mortazawi SMA. Meladinine und UVA bei Vitiligo, Psoriasis, Parapsoriasis und Akne vulgaris. Dermatol Monatsschr 1972; 158:908-9. Mortazawi SMA, Oberste-Lehn H. Lichtsensibilisatoren und ihre therapeutischen Fahigkeiten. Z Haut-Geschl Kr 1973;48:1-9. Wiskemann A. Die neuere Entwicklung der Lichttherapie. Dermatol Wochenschr 1963;147:377-83. Forck G. Ganzkorperbestrahlung mit UV-Licht. Aufbau einer neuartigen Anlage. Dermatol Wochenschr 1964;150:290-4. Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med 1974;291:1207-11. Bernhard JD. Commentary on oral methoxsalen photochemotherapy for the treatment of psoriasis: A cooperative clinical trial: from napkin notes to notabilia. J Invest Dermatol 1989; 92(Suppl):154S-6S. Melski JW, Tanenbaum L, Parrish JA, Fitzpatrick TB, Bleich HL, and 28 participating investigators. Oral methoxsalen photochemotherapy for the treatment of psoriasis: a cooperative clinical trial. J Invest Dermatol 1977;68:328-35. Honigsmann H, Jaschke E, Gschnait F, Brenner W, Fritsch P, Wolff K. 5-Methoxypsoralen (Bergapten) in photochemotherapy of psoriasis. Br J Dermatol 1979;101:369-78. Alderson HE. Heliotherapy in psoriasis. Arch Dermatol 1923;8: 79-80. Goeckerman WH. The treatment of psoriasis. Northwest Med 1925;24:229-31. Wiskemann A. UVB-Phototherapie der Psoriasis mit einer fur die PUVA-Therapie entwickelten Stehbox. Z Hautkr 1978;53:633-6. van Weelden H, De La Faille HB, Young E, van der Leun JC. A new development in UVB phototherapy of psoriasis. Br J Dermatol 1988;119:11-9. Green C, Ferguson J, Lakshmipathi T, Johnson BE. 311 nm UVB phototherapyan effective treatment for psoriasis. Br J Dermatol 1988;119:691-6.

930 Roelandts

J AM ACAD DERMATOL JUNE 2002

45. Edelson R, Berger C, Gasparro F, Jegasothy B, Heald P, Wintroub B, et al. Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 1987;316:297-303. 46. Krutmann J, Schopf E. High-dose-UVA1 phototherapy: a novel and highly effective approach for the treatment of acute exacerbation of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 1992;176:120-2. 47. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 1992;14:275-92. 48. Gschnait F. Orale Photochemotherapie. Wien: Springer Verlag; 1982. 49. Morison WL. Phototherapy and photochemotherapy of skin disease. USA: Praeger Publishers; 1983.

50. Grossweiner LI. The science of phototherapy. Boca Raton (FL): CRC Press; 1994. 51. Zanolli MD, Feldman SR, Clark AR, Fleischer AB. Phototherapy treatment protocols. Carnforth (UK): Parthenon Publishing Group; 2000. 52. Krutmann J, Honigsmann H, Elmets CA, Bergstresser PR. Derma tological phototherapy and photodiagnostic methods. Berlin: Springer Verlag; 2001. 53. Cremer RJ, Perryman PW, Richards DH. Inuence of light on the hyperbilirubinemia of infants. Lancet 1958;1:1094-7. 54. Lewy AJ, Khern HA, Rosenthal NE, Wehr TA. Bright articial light treatment of a manic-depressive patient with a seasonal mood cycle. Am J Psychiatry 1982;139:1496-8. 55. Rosenthal NE, Sack DA, Gillin JC. Seasonal affective disorders: a description of the syndrome and preliminary ndings with light therapy. Arch Gen Psychiatry 1984;41:72-80.