Archives of
Arch. Dermatol. Res. 266, 311-314 (1979)
Deermatological search
9 Springer-Verlag 1979
Short Communications
Giant Langerhans Cells Induced by Psoralen and Ultraviolet Radiation Lennart Juhlin 1 and Walter B. Shelley 2 1 Departments of Dermatology, University Hospital, S-75014 Uppsala, Sweden 2 University of Pennsylvania, Philadelphia, USA
Treatment of psoriasis with psoralens and long-wave ultraviolet radiation ( 3 2 0 - 4 4 0 nm, UVA) is an effective treatment. The risk that it might induce cutaneous carcinoma has recently been discussed [6, 7]. In Uppsala we have used photochemotherapy with trioxsalen baths (0.05 % trioxsalen dissolved in 100 ml ethylalcohol added to 1501 of water at 37~ for 15 min followed by irradiation with dysprosium lamps with a high intensity (13 mW/cm 2) in the UV-A region [1]. The lamps also emitted UV-B (295 - 320 nm, 0.7 mW/cm 2) with a peak at 313 nm. The regimen has been used for the treatment of patients with psoriasis and early mycosis fungoides [1, 2]. The first days the dose given was about 75 % of the minimal erythemal dose. It is the UV-A part of the irradiation ( 0 . 4 - 1 . 2 J) that limits the time ( 1 0 - 3 0 s ) needed to produce a minimal erythemal dose. The irradiation time is the following weeks slowly increased to 1 - 3 min. In eight patients with psoriasis and six with mycosis fungoides razor blade biopsies were taken from non-involved skin on the arms for studies of the Langerhans cells before and about once a week during treatment. The biopsies were treated and stained for Langerhans cells with the ATP-as, gold sodium thiomalate, and paraphenylenediamine methods [3]. In five of the patients with psoriasis one arm was not bathed but only irradiated with a minimum erythemal dose ( 0 . 2 - 0.8 J of UV-B) from the same lamps. The dose was gradually increased from 1 - 3 min exposure time to 10 min. Increased pigmentation was evident on the exposed areas after some days. A small non-psoriatic area on both arms was covered and used as control. Regular Langerhans cells were seen in non-irradiated psoralen-bathed skin (Fig. 1). In the normal appearing skin of patients with psoriasis and mycosis fungoides treated with PUVA bath a clear change in the morphology and the number of Langerhans cells was evident already after one week. It become more striking after 2 - 3 weeks of treatment. There were few but big Langerhans cells (Fig. 2). Their size was 2 - 4 times larger than that normally seen. They were usually elongated and bizarre (Fig. 3). In the irradiated but non-psoralen-treated skin the morphology was normal but after 3 weeks irradiation some giant cells were occasionally seen together with normal-appearing Langerhans cells. 0340-3696/79/0266/0311/$1.00
Fig. 1. Normal Langerhans cells of psoralen bathed but non-irradiated unaffected skin in a patient psoriasis. ATP-ase stain x 520
Fig. 2. Giant Langerhans cells in skin from the same patient treated with psoralen baths and UV irradiation for 2 weeks. ATP-ase stain x 520
Giant Langerhans Cells
313
Fig. 3. Bizarre giant Langerhanscellsin skin from the same patient after 3 weeksPUVA-bath treatment. ATP-ase strain x 520 We have looked at the Langerhans cells in various skin disorders from several hundred patients. The giant bizarre cells have only been seen in one patient with discoid LE and in two patients which were extremly sensitive to both UV-B and UV-A. Degenerated and swollen cells can be seen in blisters but not of this giant size. In the lesions of mycosis fungoides, the cells usually are swollen and somewhat enlarged when viewed with our techniques. With the fluorescent H L A - D R antigen technique the cells looked clumsy but not enlarged [4]. Destruction of the Langerhans cells appears to act as a focus to development of Pautrier microabscesses [5]. If the Langerhans cell is central in the pathogenesis of mycosis fungiodes the change in number of cells and their morphology by irradiation might be of importance for the therapeutic effect. Our findings of few but giant Langerhans cells is also of interest when one is considering the potential carcinogenic effects of PUVA. Do they represent a premalignant sign or the prelude to destructive removal of the essential arm of defence against the light-induced carcinoma? References 1. Fischer, T., Alsins, J. : Treatment of psoriasis with trioxsalen baths and dysprosium lamps. Acta Derm. Venerol. (Stockh.) 56, 383-390 (1976) 2. Fischer, T., Skogh, M.: Treatment of parapsoriasis en plaques, mycosis fungiodes, and S6zary's syndrome with trioxsalen baths followed by ultraviolet light. Acta Derm. Venerol. (Stockh.) 59, 171 -- 173 (1979)
314
L. Juhlin and W. B. Shelley
3. Juhlin, L., Shelley, W. B. : New staining techniques for the Langerhans cell. Acta Derm. Venerol. (Stockh.) 57, 289-296 (1977) 4. Malmngs Tjernlund, U. : Epidermal expression of HLA-DR antigens in mycosis fungiodes. Arch. Dermatol. Res. 261, 81-86 (1978) 5. Rowden, G., Phillips, T. M., Lewis, M. G., Wilkinson, R. K. : Target role of Langerhans cells in mycosis fungiodes: Transmission and immuno-electron microscopic studies. J. Cutan. Pathol. (1979 (in press) 6. Shuster, S.: Photochemotherapy for psoriasis. Lancet 1979I, 1146 7. Stern, R. S., Thibodeau, L. A., Kleinerman, R. A., Parrish, J. A., Fitzpatrick, T. B. and 22 participating investigators: Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis. N. Engl. J. Med. 300, 809-813 (1979) Received August 16, 1979
Arch. Dermatol. Res. 266, 311-314 (1979)
Deermatological search
9 Springer-Verlag 1979
Short Communications
Giant Langerhans Cells Induced by Psoralen and Ultraviolet Radiation Lennart Juhlin 1 and Walter B. Shelley 2 1 Departments of Dermatology, University Hospital, S-75014 Uppsala, Sweden 2 University of Pennsylvania, Philadelphia, USA
Treatment of psoriasis with psoralens and long-wave ultraviolet radiation ( 3 2 0 - 4 4 0 nm, UVA) is an effective treatment. The risk that it might induce cutaneous carcinoma has recently been discussed [6, 7]. In Uppsala we have used photochemotherapy with trioxsalen baths (0.05 % trioxsalen dissolved in 100 ml ethylalcohol added to 1501 of water at 37~ for 15 min followed by irradiation with dysprosium lamps with a high intensity (13 mW/cm 2) in the UV-A region [1]. The lamps also emitted UV-B (295 - 320 nm, 0.7 mW/cm 2) with a peak at 313 nm. The regimen has been used for the treatment of patients with psoriasis and early mycosis fungoides [1, 2]. The first days the dose given was about 75 % of the minimal erythemal dose. It is the UV-A part of the irradiation ( 0 . 4 - 1 . 2 J) that limits the time ( 1 0 - 3 0 s ) needed to produce a minimal erythemal dose. The irradiation time is the following weeks slowly increased to 1 - 3 min. In eight patients with psoriasis and six with mycosis fungoides razor blade biopsies were taken from non-involved skin on the arms for studies of the Langerhans cells before and about once a week during treatment. The biopsies were treated and stained for Langerhans cells with the ATP-as, gold sodium thiomalate, and paraphenylenediamine methods [3]. In five of the patients with psoriasis one arm was not bathed but only irradiated with a minimum erythemal dose ( 0 . 2 - 0.8 J of UV-B) from the same lamps. The dose was gradually increased from 1 - 3 min exposure time to 10 min. Increased pigmentation was evident on the exposed areas after some days. A small non-psoriatic area on both arms was covered and used as control. Regular Langerhans cells were seen in non-irradiated psoralen-bathed skin (Fig. 1). In the normal appearing skin of patients with psoriasis and mycosis fungoides treated with PUVA bath a clear change in the morphology and the number of Langerhans cells was evident already after one week. It become more striking after 2 - 3 weeks of treatment. There were few but big Langerhans cells (Fig. 2). Their size was 2 - 4 times larger than that normally seen. They were usually elongated and bizarre (Fig. 3). In the irradiated but non-psoralen-treated skin the morphology was normal but after 3 weeks irradiation some giant cells were occasionally seen together with normal-appearing Langerhans cells. 0340-3696/79/0266/0311/$1.00
Fig. 1. Normal Langerhans cells of psoralen bathed but non-irradiated unaffected skin in a patient psoriasis. ATP-ase stain x 520
Fig. 2. Giant Langerhans cells in skin from the same patient treated with psoralen baths and UV irradiation for 2 weeks. ATP-ase stain x 520
Giant Langerhans Cells
313
Fig. 3. Bizarre giant Langerhanscellsin skin from the same patient after 3 weeksPUVA-bath treatment. ATP-ase strain x 520 We have looked at the Langerhans cells in various skin disorders from several hundred patients. The giant bizarre cells have only been seen in one patient with discoid LE and in two patients which were extremly sensitive to both UV-B and UV-A. Degenerated and swollen cells can be seen in blisters but not of this giant size. In the lesions of mycosis fungoides, the cells usually are swollen and somewhat enlarged when viewed with our techniques. With the fluorescent H L A - D R antigen technique the cells looked clumsy but not enlarged [4]. Destruction of the Langerhans cells appears to act as a focus to development of Pautrier microabscesses [5]. If the Langerhans cell is central in the pathogenesis of mycosis fungiodes the change in number of cells and their morphology by irradiation might be of importance for the therapeutic effect. Our findings of few but giant Langerhans cells is also of interest when one is considering the potential carcinogenic effects of PUVA. Do they represent a premalignant sign or the prelude to destructive removal of the essential arm of defence against the light-induced carcinoma? References 1. Fischer, T., Alsins, J. : Treatment of psoriasis with trioxsalen baths and dysprosium lamps. Acta Derm. Venerol. (Stockh.) 56, 383-390 (1976) 2. Fischer, T., Skogh, M.: Treatment of parapsoriasis en plaques, mycosis fungiodes, and S6zary's syndrome with trioxsalen baths followed by ultraviolet light. Acta Derm. Venerol. (Stockh.) 59, 171 -- 173 (1979)
314
L. Juhlin and W. B. Shelley
3. Juhlin, L., Shelley, W. B. : New staining techniques for the Langerhans cell. Acta Derm. Venerol. (Stockh.) 57, 289-296 (1977) 4. Malmngs Tjernlund, U. : Epidermal expression of HLA-DR antigens in mycosis fungiodes. Arch. Dermatol. Res. 261, 81-86 (1978) 5. Rowden, G., Phillips, T. M., Lewis, M. G., Wilkinson, R. K. : Target role of Langerhans cells in mycosis fungiodes: Transmission and immuno-electron microscopic studies. J. Cutan. Pathol. (1979 (in press) 6. Shuster, S.: Photochemotherapy for psoriasis. Lancet 1979I, 1146 7. Stern, R. S., Thibodeau, L. A., Kleinerman, R. A., Parrish, J. A., Fitzpatrick, T. B. and 22 participating investigators: Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis. N. Engl. J. Med. 300, 809-813 (1979) Received August 16, 1979
