Pharmacology and Therapeutics
The Effect of Superficial X-Radiation on Epidermal Langerhans Cells in Human Skin E. K. Edv^/ards, Jr., M.D., and E. K. Edwards, Sr., M.D.
Abstract: The anti-inflammatory effects of superficial x-tadiaticn may be due, in part, tc their depleting effect on the Langerhans cell in the epidermis.
Dermatologists bave successfully used superficial x-ray therapy (S-XRT) for the treatment of more tban 80 benign and malignant disorders since 1899.'- During tbe last 4 years there bas been a steady re-kindled interest in tbe use of both S-XRT and grenz rays for tbe treatment of a variety of malignant as well as recalcitrant benign dermatoses, including allergic contact dermatitis, cbronic eczemas, and psoriasis. These are still safe and useful modalities in our armamentarium provided certain precautions are taken.^•'' It was recently sbown tbat botb grenz radiation (tbat radiation produced at voltages of 8-15 [kilovolt (peak)] and soft x-radiation (generated at voltages of 20 to 30 kVp) influence the cutaneous immune system by tbeir reduction or alteration effect on epidermal Langerhans cells. ^•'' Langerhans cells, dendritic cells found in an epidermal suprabasal location, make up 4% of the epidermis and are derived from bone marrow stem cells. They are related both functionally and immunologically to monocytes/macrophages and histiocytes.' They possess immune-associated antigens (la-antigens) and surface receptors for the Fc portion of IgG and tbe C3 component of compliment.'""'^ Langerbans cells can be demonstrated with the monoclonal antibodies Anti-Leu-6, HLA-DR, ATPase, and S-100 protein.'^"'* Because most dermatologists in private practice do not bave access to an apparatus that generates x-rays in the soft range but many have pyrex-windowed units that operate in the superficial range (ie, 60-110 kVp), we thought it would be
From Ridge-Edwards Dermatology Center, Pompano Beach, Florida. Address correspondence to: E. K. Edwards, Jr., M.D., Ridge-Edwards Dermatology Center, 1800 North Federal Highway, Pompano Beach, FL 33062. December 7990, Vol. 29, No. 10
interesting to evaluate the effects of superficial x-rays on the cutaneous immune systern, more specifically the Langerhans cells in human skin, using the dose that a dermatologist would normally use in the treatment of a benign dermatosis, tbat is, 100 roentgen. Materials and Methods Four healthy volunteers were included in the study, two men and two women. Each volunteers had three 3-mm puneh biopsy specimens taken from the following sites: 1) nonexposed gluteal skin (control); 2) an adjacent area of skin measuring 5 em in diameter, which 24 hours previously had received 100 rads of superficial x-radiation; and, 3) an adjacent area of skin also measuring 5 cm, whieh one week previously had received lOOR of superficial x-radiation. The following physical factors were used: standard pyrex-windowed x-ray unit (Profex, Chicago, IL), 90 kVp, 5 mA, no additional filtration, HVL = 0.7 mm Al, TSD = 15 cm, cone diameter = 5 em. The slides were fixed in formalin and the S-100 protein immunoperoxidase technique described elsewhere was used."' The number of Langerhans eells per high power field was counted in each biopsy specimen by a dermatopathologist in blind fashion.
Results Table 1 illustrates the results obtained. At 24 hours there was an average decrease of S-100 {+) dendritic cells of 67, 54, 48, and 40% respectively. At 1 week there was an average decrease of S-100 (-H) dendritic cells of 91, 80, 66, and 80% respectively. Discussion Superficial x-radiation in the dose schedule commonly used by the dermatologist reduces the number of S-100 (-I-) dendritic cells by an average of 80% one week postirradiation. Previous immunohistochemical studies by others using grenz and soft x-radiation also show a decrease in the number of LCs postirradiation. These studies were done simultaneously witb electron mi731
732
International Journal of Dermatology • December 1990
Table 1. Average Number of S-100 (+) Dendritic Cells per High Power Field
Patient
Site A
Site B
Site C
1 2 3 4
11 15 12 10
3 7
1 3 4 2
8 6
The numbers represent the average number of S-100 (4-) dendritie cells per high power field in which A = eontrol gluteal skin, B = irradiated adjaeent site at 24 hours, and, C = irradiated adjacent site at 7 days.
croscopy to demonstrate that there was an actual decrease in the number of Langerhans cells as opposed to solely surface marker alteration of them.'-^ In our study, S-100 (-I-) dendritic cells, which were seen in the basal cell layer, could have represented melanocytes, so these cells were not included in numeration of Langerhans cells; only those cells that were in a suprabasal position were considered to be Langerhans cells. There appeared to be no alteration in the morphology of dendritic cells that remained after irradiation. Future studies can be performed using different voltages, amperage, filtration, dosimetry, and monoclonal antibodies. In summary, the immunologic effects produced by superficial x-radiation may be secondary to their effects of depletion and/or surface marker alteration on Langerhans cells in skin. A cknowledgment Neal S. Penneys, M.D., Ph.D., Miami, Florida cooperated in this study.
Vol. 29
References 1. Leigh S. Use of Roentgen rays in inflammatory disease. Am J X-rays. 1899;4:559. 2. Pohle S. Clinieal Radiation Therapy. Philadelphia: Lea and Febiger, 1950:760. 3. Edwards Jr., EK, Edwards Sr., EK. Grenz ray therapy: a commentary and update. Int J Dermatol. (in press). 4. Edwards Jr., EK, Edwards Sr., EK. Superfieial x-ray therapy: Pyrex vs beryllium window units. Int J Dermatol. (in press). 5. Lindelof B, Forslind B. Electron mieroseopie observation of Langerhans eells in human skin irradiated with grenz rays. Photoderm. 1985;2:367-37L 6. Groh V, Meyer J. Soft x-rays irradiation influences the integrity of Langerhans cells. Dermatologica. 1984;168:53-60. 7. Tamaki K, StingI G, Katz S. The origin of Langerhans eells. J Invest Dermatol. 1980;74:309-311. 8. Baer R. Introduetory remarks to the session on Langerhans eells. J Invest Dermatol. 198O;74:3O7-3O8. 9. StingI G, Katz S, Shevach E. Amalagous functions of macrophages and Langerhans eells in the initiation of the immune response. J Invest Dermatol. 1978;71:59-64. 10. Bergstresser P, Toews G, Gillian J. Unusual numbers and distribution of Langerhans eells in skin with unique immunologie properties. J Invest Dermatol. 1980;74:312-314. 11. Rowden G, Lewis M, Sullivan A. la antigens expression on human Langerhans cells. Nature. 1977;268:247-248. 12. StingI G, Sehreiner E, Piehler W. Epidermal Langerhans bear Fc and C3 receptors. Nature. 1977;268:245-246. 13. Dubert L, Picard O, Bugat M. Speeifieity of monoclonal antibody anti-T-6 for Langerhans eells in human skin. Br J Dermatol. l983;106:287-289. 14. Hsu R, Raine L, Fanzer H. The use of avidin-biotin peroxidase complex in immunoperoxidase teehniques: a eomparison between ABC and unlabeled PAP procedures. J Histoehem Cytochem. 1981;29:577-.587. 15. Edwards Jr, EK, Edwards Sr, EK, Frank B, et al. The effect of an ultraproteetive sunscreen on Langerhans eell alteration in human skin. Int J Dermatol. 1986;25:327-328. 16. Doherty M, Russo G, Jolly H, et al. Immunoenzyme techniques in dermatopatholody. J Amer Aead Dermatol 1989;20:827-837.
History of Pemphigus The eigfities of the last century were the beginning of a new era in pemphigus research. Auspitz created a new system of skin diseases in 1880-1885. There were nine classes, the seventh of which was subdivided into the families of keratonoses, chromatoses and akanthoses (spelt with a 'k'). The latter were subdivided further into hyperakanthoses, parakanthoses and akantholyses. Pemphigus was listed under acantholyses (the modern spelling) and the blister formation in pemphigus was called acantholytic, as opposed to spongiotic, blister formation in inflammatory conditions of the skin. Loss of the intercellular bridges and loss of cohesion between the epidermal cells was considered by Auspitz to be responsible for blister formation. He described, part of fhe cylindrical basal layer of cells remaining on the floor of the blister, i.e. suprabasal blister formation, and he gave it a separate name, acantholysis. For this reason Auspitz's description must be considered a landmark in pemphigus research. Unfortunately, his system did not appeal to the dermatological world of the time nor did acantholysis—both were buried with him. There were earlier equivocal reports on intraepithelial blister formation, e.g. Haight's in 1868. Louis Adolphus Duhring from Philadelphia described a new entity in 1884 and called it dermatitis herpetiformis. fHeinrich Kobner of Breslau (now Wroclaw), one of Hebra's Jewish pupils, created the term epidermolysis bullosa hereditaria in literal allusion to Auspitz's acantholysis in 1886. Both ferms were not immediately accepted, and one can easily imagine how confusing the whole field appeared af this poinf.—Wojnarowska F, Briggaman RA. Management of blistering diseases. New York, Raven Press 7990:3.
The Effect of Superficial X-Radiation on Epidermal Langerhans Cells in Human Skin E. K. Edv^/ards, Jr., M.D., and E. K. Edwards, Sr., M.D.
Abstract: The anti-inflammatory effects of superficial x-tadiaticn may be due, in part, tc their depleting effect on the Langerhans cell in the epidermis.
Dermatologists bave successfully used superficial x-ray therapy (S-XRT) for the treatment of more tban 80 benign and malignant disorders since 1899.'- During tbe last 4 years there bas been a steady re-kindled interest in tbe use of both S-XRT and grenz rays for tbe treatment of a variety of malignant as well as recalcitrant benign dermatoses, including allergic contact dermatitis, cbronic eczemas, and psoriasis. These are still safe and useful modalities in our armamentarium provided certain precautions are taken.^•'' It was recently sbown tbat botb grenz radiation (tbat radiation produced at voltages of 8-15 [kilovolt (peak)] and soft x-radiation (generated at voltages of 20 to 30 kVp) influence the cutaneous immune system by tbeir reduction or alteration effect on epidermal Langerhans cells. ^•'' Langerhans cells, dendritic cells found in an epidermal suprabasal location, make up 4% of the epidermis and are derived from bone marrow stem cells. They are related both functionally and immunologically to monocytes/macrophages and histiocytes.' They possess immune-associated antigens (la-antigens) and surface receptors for the Fc portion of IgG and tbe C3 component of compliment.'""'^ Langerbans cells can be demonstrated with the monoclonal antibodies Anti-Leu-6, HLA-DR, ATPase, and S-100 protein.'^"'* Because most dermatologists in private practice do not bave access to an apparatus that generates x-rays in the soft range but many have pyrex-windowed units that operate in the superficial range (ie, 60-110 kVp), we thought it would be
From Ridge-Edwards Dermatology Center, Pompano Beach, Florida. Address correspondence to: E. K. Edwards, Jr., M.D., Ridge-Edwards Dermatology Center, 1800 North Federal Highway, Pompano Beach, FL 33062. December 7990, Vol. 29, No. 10
interesting to evaluate the effects of superficial x-rays on the cutaneous immune systern, more specifically the Langerhans cells in human skin, using the dose that a dermatologist would normally use in the treatment of a benign dermatosis, tbat is, 100 roentgen. Materials and Methods Four healthy volunteers were included in the study, two men and two women. Each volunteers had three 3-mm puneh biopsy specimens taken from the following sites: 1) nonexposed gluteal skin (control); 2) an adjacent area of skin measuring 5 em in diameter, which 24 hours previously had received 100 rads of superficial x-radiation; and, 3) an adjacent area of skin also measuring 5 cm, whieh one week previously had received lOOR of superficial x-radiation. The following physical factors were used: standard pyrex-windowed x-ray unit (Profex, Chicago, IL), 90 kVp, 5 mA, no additional filtration, HVL = 0.7 mm Al, TSD = 15 cm, cone diameter = 5 em. The slides were fixed in formalin and the S-100 protein immunoperoxidase technique described elsewhere was used."' The number of Langerhans eells per high power field was counted in each biopsy specimen by a dermatopathologist in blind fashion.
Results Table 1 illustrates the results obtained. At 24 hours there was an average decrease of S-100 {+) dendritic cells of 67, 54, 48, and 40% respectively. At 1 week there was an average decrease of S-100 (-H) dendritic cells of 91, 80, 66, and 80% respectively. Discussion Superficial x-radiation in the dose schedule commonly used by the dermatologist reduces the number of S-100 (-I-) dendritic cells by an average of 80% one week postirradiation. Previous immunohistochemical studies by others using grenz and soft x-radiation also show a decrease in the number of LCs postirradiation. These studies were done simultaneously witb electron mi731
732
International Journal of Dermatology • December 1990
Table 1. Average Number of S-100 (+) Dendritic Cells per High Power Field
Patient
Site A
Site B
Site C
1 2 3 4
11 15 12 10
3 7
1 3 4 2
8 6
The numbers represent the average number of S-100 (4-) dendritie cells per high power field in which A = eontrol gluteal skin, B = irradiated adjaeent site at 24 hours, and, C = irradiated adjacent site at 7 days.
croscopy to demonstrate that there was an actual decrease in the number of Langerhans cells as opposed to solely surface marker alteration of them.'-^ In our study, S-100 (-I-) dendritic cells, which were seen in the basal cell layer, could have represented melanocytes, so these cells were not included in numeration of Langerhans cells; only those cells that were in a suprabasal position were considered to be Langerhans cells. There appeared to be no alteration in the morphology of dendritic cells that remained after irradiation. Future studies can be performed using different voltages, amperage, filtration, dosimetry, and monoclonal antibodies. In summary, the immunologic effects produced by superficial x-radiation may be secondary to their effects of depletion and/or surface marker alteration on Langerhans cells in skin. A cknowledgment Neal S. Penneys, M.D., Ph.D., Miami, Florida cooperated in this study.
Vol. 29
References 1. Leigh S. Use of Roentgen rays in inflammatory disease. Am J X-rays. 1899;4:559. 2. Pohle S. Clinieal Radiation Therapy. Philadelphia: Lea and Febiger, 1950:760. 3. Edwards Jr., EK, Edwards Sr., EK. Grenz ray therapy: a commentary and update. Int J Dermatol. (in press). 4. Edwards Jr., EK, Edwards Sr., EK. Superfieial x-ray therapy: Pyrex vs beryllium window units. Int J Dermatol. (in press). 5. Lindelof B, Forslind B. Electron mieroseopie observation of Langerhans eells in human skin irradiated with grenz rays. Photoderm. 1985;2:367-37L 6. Groh V, Meyer J. Soft x-rays irradiation influences the integrity of Langerhans cells. Dermatologica. 1984;168:53-60. 7. Tamaki K, StingI G, Katz S. The origin of Langerhans eells. J Invest Dermatol. 1980;74:309-311. 8. Baer R. Introduetory remarks to the session on Langerhans eells. J Invest Dermatol. 198O;74:3O7-3O8. 9. StingI G, Katz S, Shevach E. Amalagous functions of macrophages and Langerhans eells in the initiation of the immune response. J Invest Dermatol. 1978;71:59-64. 10. Bergstresser P, Toews G, Gillian J. Unusual numbers and distribution of Langerhans eells in skin with unique immunologie properties. J Invest Dermatol. 1980;74:312-314. 11. Rowden G, Lewis M, Sullivan A. la antigens expression on human Langerhans cells. Nature. 1977;268:247-248. 12. StingI G, Sehreiner E, Piehler W. Epidermal Langerhans bear Fc and C3 receptors. Nature. 1977;268:245-246. 13. Dubert L, Picard O, Bugat M. Speeifieity of monoclonal antibody anti-T-6 for Langerhans eells in human skin. Br J Dermatol. l983;106:287-289. 14. Hsu R, Raine L, Fanzer H. The use of avidin-biotin peroxidase complex in immunoperoxidase teehniques: a eomparison between ABC and unlabeled PAP procedures. J Histoehem Cytochem. 1981;29:577-.587. 15. Edwards Jr, EK, Edwards Sr, EK, Frank B, et al. The effect of an ultraproteetive sunscreen on Langerhans eell alteration in human skin. Int J Dermatol. 1986;25:327-328. 16. Doherty M, Russo G, Jolly H, et al. Immunoenzyme techniques in dermatopatholody. J Amer Aead Dermatol 1989;20:827-837.
History of Pemphigus The eigfities of the last century were the beginning of a new era in pemphigus research. Auspitz created a new system of skin diseases in 1880-1885. There were nine classes, the seventh of which was subdivided into the families of keratonoses, chromatoses and akanthoses (spelt with a 'k'). The latter were subdivided further into hyperakanthoses, parakanthoses and akantholyses. Pemphigus was listed under acantholyses (the modern spelling) and the blister formation in pemphigus was called acantholytic, as opposed to spongiotic, blister formation in inflammatory conditions of the skin. Loss of the intercellular bridges and loss of cohesion between the epidermal cells was considered by Auspitz to be responsible for blister formation. He described, part of fhe cylindrical basal layer of cells remaining on the floor of the blister, i.e. suprabasal blister formation, and he gave it a separate name, acantholysis. For this reason Auspitz's description must be considered a landmark in pemphigus research. Unfortunately, his system did not appeal to the dermatological world of the time nor did acantholysis—both were buried with him. There were earlier equivocal reports on intraepithelial blister formation, e.g. Haight's in 1868. Louis Adolphus Duhring from Philadelphia described a new entity in 1884 and called it dermatitis herpetiformis. fHeinrich Kobner of Breslau (now Wroclaw), one of Hebra's Jewish pupils, created the term epidermolysis bullosa hereditaria in literal allusion to Auspitz's acantholysis in 1886. Both ferms were not immediately accepted, and one can easily imagine how confusing the whole field appeared af this poinf.—Wojnarowska F, Briggaman RA. Management of blistering diseases. New York, Raven Press 7990:3.
