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Extracorporeal photopheresis in the treatment of acute graft-versus-host disease
Journal of the American Academy of Dermatology Volume 36, Number 5, Part 1
agnosis of pulmonary sarcoidosis. Treatment included oral cyclophosphamide, 100 mg/day, to fimit the use of systemic prednisone because of the patient's diabetes mellitus. After several months, nearly all of her thousands of cutaneous and oral keratoacanthomas cleared without scarring, leaving hyperpigmentation and prominent follicular orifices (Figs. 1 and 2). The patient was maintained on this reghnen of cyclophosphamide for 8 months until treatment was discontinued after remission of her sarcoidosis. Approximately 10 weeks later, her keratoacanthomas progressively returned. Cyclophosphamide, 50 mg/day, was started, but ~rther progression of her lesions occurred during the next month. After the cyclophosphamide dosage was increased to 100 mg/day, no further progression occurred. After several months on this dosage, clearing of nearly all her keratoacanthomas occurred again. This regimen was maintained for 7 months, at which time the cyclophosphamide was discontinued to treat a severe cellulitis. DISCUSSION Therapies for generalized keratoacanthomas have been disappointing. The most successful are systemic retinoids 2, 3 and methotrexate, 4' 5 although this
Brief communications
787
patient failed to respond to them. Our patient noted resolution of her extensive lesions with cyclophosphamide, recurrence on withdrawal, and another remission on reinstitution of cyclophosphamide. In spite o f this remarkable improvement, the significant side effects o f cyclophosphamide, including a cumulative dose-related risk of leukemic disorders and hemorrhagic cystitis, should restrict the use of cyclophosphamide until other regimens have failed. REFERENCES 1. Jaber PW, Cooper PH, Greer KE. Generalized eruptive keratoacanthoma of Grzybowski. J Am Acad Dermatol 1993;29:299-304. 2. Street ML, White JW Jr, Gibson LE. Multiple keratoacanthomas treated with oral retinoids. J Am Acad Dermatol 1990;23:862-6. 3. Benoldi D, Alinovi A. Multiple persistent keratoacanthomas: treatment with oral etretinate. J Am Acad Dermatol 1984;10:1035-8. 4. Tarnowski WM. Multiple keratoacanthomata: response of a case to systemic,chemotherapy. Arch Dermatol 1966;94:7480. 5. Kestel JL Jr, Blair DS. Keratoacanthoma treated with methotrexate. Arch Dermatol 1973;108:723-4.
Extracorporeal photopheresis in the treatment of acute graft-versus-host disease Heike I. Richter, MD, a Helger Stege, MD, a Thomas Ruzicka, MD, a Dietmar Soehngen, MD, b Axel Heyll, MD, b and Jean Krutmann, M D a Diisseldorf Germany A major advance in the management o f severe hematologic disorders such as aplastic anemia, severe combined immunodeficiency, and leukemia has been allogeneic bone marrow transplantation (BMT). 1 Successful BMT, however, is frequently
From Clinical and ExperimentalPhotodermatology,Departments of Dermatologya and Hematology?Heinrich-HeineUniversity. Reprint requests:Jean Krutmann,MD, Departmentof Dermatology, H.-HeineUniversity,Moorenstr.5, 40225 Duesseldorf,Germany. J Am Acad Dermatol 1997;36:787-9. Copyright© 1997 by the AmericanAcademyof Dermatology,Inc. 0190-9622/97/$5.00+ 0 16/54/80018
impeded by the development o f acute graft-versushost disease (GVHD), which m a y occur in 10% to 60% o f recipients, even when the donor is a sibling who is identical at the major histocompatibility (HLA) locus. 1,2 G V H D is either an acute (day +100) disease. Acute G V H D is characterized b y high morbidity and mortality. Only certain tissues and cell types are susceptible to damage from G V H D (i.e., the gastrointestinal mucosa and its extension into the biliary tree, the bronchial mucosa, and in particular the skin). Skin manifestations in acute G V H D range from a subtle, blanchable, erythematous, macular or
788
Brief communications
papular eruption to the toxic epidermal necrolysis like form of acute GVHD with generalized erythema and blister formation. 2-5 Current treatment of acute GVHD consists of a combination of immunosuppressive drugs, including cyclosporine, glucocorticosteroids, and azathioprine. 3'6 In some patients these drugs, even if given in high doses, fail to suppress the development of skin disease. Oral photochemotherapy (PUVA) may be effective as an adjunctive treatment of chronic GVHD. 7-9However, there is increasing evidence that PUVA therapy for immunosuppressed patients may increase their risk for the development of skin cancer, and PUVA therapy for GVHD has been associated with the rapid development of squamous cell carcinomas, m-le Similar to PUVA therapy, extracorporeal photochemotherapy or extracorporeal photopheresis (ECP) is based on the combined action of psoralen (methoxsalen) and UVA radiation. 13 In ECP, however, only the patient's T cells are exposed to UV radiation. Therefore ECP is not associated with an increased risk of skin cancer, even if combined with immunosuppressive drugs. We report the successful use of ECP in the management of a patient with acute GVHD. CASE REPORT
A 26-year-old man with chronic myelocytic leukemia received an allogeneic bone marrow transplant from his HLA-compatible sister after total body irradiation (10 Gy) and high-dose cyclophosphamide (2 x 60 mg/kg of body weight). GVHD prophylaxis consisted of cyclosporine and a brief course of methotrexate. On day 22 after BMT acute GVHD developed that involved skin (grade IB) and liver (grade II), which resolved by day 43 with prednisolone treatment. After cessation of prednisolone therapy (day 51), the patient had a relapse of GVHD (grade II-llI) with fever, cough, Sjtgren syndrome like signs, lichenoid papules, a pruritic maculopapular rash, and ulcerations of the buccal mucosa and tongue. Because his acute GVHD could not be controlled with cyclosporine (550 mg/day) in combination with steroids (60 mg/day), ECP was performed every 4 weeks on two consecutive days as previously described. 13 After three cycles of ECP his cutaneous symptoms, his eruption, and his mucosal lesions were clearing. Systemic immunosuppression was gradually tapered. Complete clearance was observed after 13 cycles. After cessation of ECP, GVHD did not recur, and the patient has returned to work.
Journal of the AmericanAcademyof Dermatology May 1997 DISCUSSION
To our knowledge this is the first report of successful treatment of acute GVHD with ECP. In comparison to PUVA therapy, ECP has several advantages. ECP avoids methoxsalen plus UVA radiation of the patient's skin and may not be associated with an increased risk for the development of skin cancer. 1°-13 Recently, two patients with erythrodermic cutaneous T-cell lymphoma have been described, in whom squamous cell carcinomas developed while they were undergoing ECP. The skin cancer in these patients, however, may have resulted from factors other than ECP (e.g., previous therapy with PUVA, topical treatment with mechlorethamine, recreational habits, and the patient's age).14 PUVA treatment requires oral administration of methoxsalen three to four times per week, which, in a substantial percentage of patients (up to 20%) may cause nausea and vomiting. 15 In contrast, ECP requires oral methoxsalen administration for only 2 consecutive days at 4-week intervals; therefore psoralen-induced side effects are significantly reduced. The mechanism underlying clinical responses to ECP is not completely understood. However, PUVA is known to interact with cellular DNA, lipids, and proteins. It appears that cell surface changes, induced directly or indirectly by methoxsalen and UVA, render cells susceptible to immune surveillance and destruction. In addition, changes in antigen presentation caused by altered processing of cellular proteins or enhanced expression of class I major histocompatibility complex may also contribute. 13 Although originally developed for the treatment of cutaneous T-cell lymphoma, ECP has also been used for the management of other T-cell mediated and autoimmune diseases, including pemphigus vulgaris, rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, and chronic GVHD. 16-2° In addition, ECP is being increasingly used together with cyclosporine or glucocorticosteroids (or both) to prevent organ rejection in patients with heart or kidney transplants. 21-~ The present observation suggests that ECP may also be used in the management of patients with acute GVHD. In view of the increasing risk of GVHD caused by the frequent use of bone marrow from unrelated donors,I, 3 it will be of interest to assess whether ECP may also be used as a prophylactic approach in bone marrow transplant recipients to prevent GVHD.
Journal of the American Academy of Dermatology Volume 36, Number 5, Part 1
Brief communications 789 13. Edelson RL, Gasparro FP. Extracorporeal photochemotherapy. In: Krutmann J, Elmets CA, editors. Photoimmunology. Oxford: Blackwell Science, 1995:23145. 14. Nehal KS, Green KB, Lim HW. Aggressive squamous cell carcinomas in patients treated with extracorporeal photopheresis for cutaneous T-cell lymphoma. Arch Dermatol 1995;131:1211-2. 15. Gschnait F. Oralphotochemotherapy. New York: Springer, 1982:18-24. t6. DaU'Amico R, Zufian F, Montini G, et al. Applications of extracorporeal photochemotherapy in "non-oncological" diseases. Int J Artif Organs 1994;16:168-72. 17. Gollnick HPM, Owsianowski M, Taube KM, et al. Unresponsive severe generalized pemphigus vulgaris successfully controlled by extracorporeal photopheresis. J Am Acad Dermatol 1993;28:122-4. 18. de Misa RF, Azana JM, Harto A, et al. Extracorporeal photochemotherapy in the treatment of severe psoriatic arthropathy. Br J Dermatol 1992;127:448. 19. Di-Spaltro FX, Cottrill C, Cahill C, et al. Extracorporeal photochemotherapy in progressive systemic sclerosis. Int J Derrnatol 1993:32:417-21. 20. Gollnick H, Owsianowski M, Siegert W, et al. Successful treatment of chronic graft-versus-host disease with extracorporeal photopheresis. Bone Marrow Transplant 1994; 14:845-8, 21. Ban- ML. Prophylactic photopheresis in cardiac transplantation. J Clin Apheresis 1994;9:228-9. 22. Dall'Amico R, Livi U, Montini A, et al. Extracorporeal photochemotherapy as adjuvant treatment on heart transplantation recipients with recurrent rejection. Transplantation In press 23. Horina JH, Mtlllegger RR, Horn S, et al. Photopheresis for renal allograft rejection [letter]. Lancet 1995;346: 6l. 24. Sunder-Plassmann G , / ) a i m / W , Knobler R, et al. Renal allograft rejection controlled by photopheresis [letter]. Lancet 1995;346:506.
REFERENCES
1. Ferrara JLM, Deeg HJ. Graft-versus-host disease. N Engl J Med 1991;324:667-74. 2. Glucksberg H, Storb R, Buckner CD, et al. Clinical manifestation of graft-versus-host disease in human recipients of marrow from HLA-matched, sibling donor. Transplantation 1974;18:459-62. 3. Storb R. Bone marrow transplantation. Transplant Proc 1995;27:2649-56. 4. Saurat J-H. Cutaneous manifestation of graft-versus-host disease. Int J Dermatol 1981;20:249-56. 5. Volc-Platzer B, Rappersberger K, Mosberger I, et al. Sequential immunohistologic analysis of skin following allogenic bone marrow transplantation. J Invest Dermatol 1988;91:162-8. 6. Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine alone for prophylaxis of acute graft-versushost disease after marrow transplantation for leukemia. N Engl J Med 1986;314:729-35. 7. Volc-Platzer B, Hoenigsmann H, Hinterberger W, et al. Photochemotherapy improves chronic cutaneous graftversus-host disease. J Am Acad Dermatol 1990;23:220-8. 8. Jampel RM, Farmer ER, Vogelsang GB, et al. PUVAtherapy for chronic cutaneous graft-versus-host disease. Arch Derrnatol 1991; 127:1673-8. 9. Deeg HJ. Photoimmunology of blood transfusion, bone marrow and organ transplantation. In: Krutmann J, Elmets CA, editors. Photoimmunology. Oxford: Blackwell Science, 1995:274-84. 10. Stern RS, Laird N, Me/ski J, et al. Cutaneous squamous cell carcinoma in patients treated with PUVA. N Engl J Med 1984;310:1156-61. 11. Stem RS, Members of the Photocbemotherapy Follow-Up Study. Genital tumors among men with psoriasis exposed to psoralen and ultraviolet A radiation (PUVA) and ultraviolet B radiation. N Engl J Med 1990;322:1093-7. 12. Altman JS, Alder SS. Development of multiple cutaneous squamous cell carcinomas during PUVA treatment for chronic graft-versus-host disease. J Am Acad Dermatol 1994;31:505-7.
Itraconazole for the treatment of tinea pedis: A dosage of 400 mg/day given for 1 week is similar in efficacy to 100 or 200 mg/day given for 2 to 4 weeks Aditya K. Gupta, MD, F R C P C , a Piet De Doncker, PhD,b Annie Heremans, MD, PhD, b Paul Stoffels, MD, b G6rald E. Pirrard, MD, PhD, c J. Decroix, MD, d M. Heenen, MD, P h D , e and Hugo Degreef, MD f Toronto, Canada, and Beerse, Likge,
Mouscron, Brussels, and Leuven, Belgium From the Department of Dermatology, University of Torontoa: the Department of Clinical Research, Janssen Research Foundation, Beerseb;the Departmentof Dermatopathology,Universityof LirgeC; Av du Parc, Mouscrond;the Department of Dermatology.Free University, B/'tlsselse; and the Department of Dermatology, Catholic University Leuven.f
Reprints are not available from the authors. J Am Acad Derrnatol 1997;36:789-92. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/97/$5.00 + 0 16/54/79668
agnosis of pulmonary sarcoidosis. Treatment included oral cyclophosphamide, 100 mg/day, to fimit the use of systemic prednisone because of the patient's diabetes mellitus. After several months, nearly all of her thousands of cutaneous and oral keratoacanthomas cleared without scarring, leaving hyperpigmentation and prominent follicular orifices (Figs. 1 and 2). The patient was maintained on this reghnen of cyclophosphamide for 8 months until treatment was discontinued after remission of her sarcoidosis. Approximately 10 weeks later, her keratoacanthomas progressively returned. Cyclophosphamide, 50 mg/day, was started, but ~rther progression of her lesions occurred during the next month. After the cyclophosphamide dosage was increased to 100 mg/day, no further progression occurred. After several months on this dosage, clearing of nearly all her keratoacanthomas occurred again. This regimen was maintained for 7 months, at which time the cyclophosphamide was discontinued to treat a severe cellulitis. DISCUSSION Therapies for generalized keratoacanthomas have been disappointing. The most successful are systemic retinoids 2, 3 and methotrexate, 4' 5 although this
Brief communications
787
patient failed to respond to them. Our patient noted resolution of her extensive lesions with cyclophosphamide, recurrence on withdrawal, and another remission on reinstitution of cyclophosphamide. In spite o f this remarkable improvement, the significant side effects o f cyclophosphamide, including a cumulative dose-related risk of leukemic disorders and hemorrhagic cystitis, should restrict the use of cyclophosphamide until other regimens have failed. REFERENCES 1. Jaber PW, Cooper PH, Greer KE. Generalized eruptive keratoacanthoma of Grzybowski. J Am Acad Dermatol 1993;29:299-304. 2. Street ML, White JW Jr, Gibson LE. Multiple keratoacanthomas treated with oral retinoids. J Am Acad Dermatol 1990;23:862-6. 3. Benoldi D, Alinovi A. Multiple persistent keratoacanthomas: treatment with oral etretinate. J Am Acad Dermatol 1984;10:1035-8. 4. Tarnowski WM. Multiple keratoacanthomata: response of a case to systemic,chemotherapy. Arch Dermatol 1966;94:7480. 5. Kestel JL Jr, Blair DS. Keratoacanthoma treated with methotrexate. Arch Dermatol 1973;108:723-4.
Extracorporeal photopheresis in the treatment of acute graft-versus-host disease Heike I. Richter, MD, a Helger Stege, MD, a Thomas Ruzicka, MD, a Dietmar Soehngen, MD, b Axel Heyll, MD, b and Jean Krutmann, M D a Diisseldorf Germany A major advance in the management o f severe hematologic disorders such as aplastic anemia, severe combined immunodeficiency, and leukemia has been allogeneic bone marrow transplantation (BMT). 1 Successful BMT, however, is frequently
From Clinical and ExperimentalPhotodermatology,Departments of Dermatologya and Hematology?Heinrich-HeineUniversity. Reprint requests:Jean Krutmann,MD, Departmentof Dermatology, H.-HeineUniversity,Moorenstr.5, 40225 Duesseldorf,Germany. J Am Acad Dermatol 1997;36:787-9. Copyright© 1997 by the AmericanAcademyof Dermatology,Inc. 0190-9622/97/$5.00+ 0 16/54/80018
impeded by the development o f acute graft-versushost disease (GVHD), which m a y occur in 10% to 60% o f recipients, even when the donor is a sibling who is identical at the major histocompatibility (HLA) locus. 1,2 G V H D is either an acute (
788
Brief communications
papular eruption to the toxic epidermal necrolysis like form of acute GVHD with generalized erythema and blister formation. 2-5 Current treatment of acute GVHD consists of a combination of immunosuppressive drugs, including cyclosporine, glucocorticosteroids, and azathioprine. 3'6 In some patients these drugs, even if given in high doses, fail to suppress the development of skin disease. Oral photochemotherapy (PUVA) may be effective as an adjunctive treatment of chronic GVHD. 7-9However, there is increasing evidence that PUVA therapy for immunosuppressed patients may increase their risk for the development of skin cancer, and PUVA therapy for GVHD has been associated with the rapid development of squamous cell carcinomas, m-le Similar to PUVA therapy, extracorporeal photochemotherapy or extracorporeal photopheresis (ECP) is based on the combined action of psoralen (methoxsalen) and UVA radiation. 13 In ECP, however, only the patient's T cells are exposed to UV radiation. Therefore ECP is not associated with an increased risk of skin cancer, even if combined with immunosuppressive drugs. We report the successful use of ECP in the management of a patient with acute GVHD. CASE REPORT
A 26-year-old man with chronic myelocytic leukemia received an allogeneic bone marrow transplant from his HLA-compatible sister after total body irradiation (10 Gy) and high-dose cyclophosphamide (2 x 60 mg/kg of body weight). GVHD prophylaxis consisted of cyclosporine and a brief course of methotrexate. On day 22 after BMT acute GVHD developed that involved skin (grade IB) and liver (grade II), which resolved by day 43 with prednisolone treatment. After cessation of prednisolone therapy (day 51), the patient had a relapse of GVHD (grade II-llI) with fever, cough, Sjtgren syndrome like signs, lichenoid papules, a pruritic maculopapular rash, and ulcerations of the buccal mucosa and tongue. Because his acute GVHD could not be controlled with cyclosporine (550 mg/day) in combination with steroids (60 mg/day), ECP was performed every 4 weeks on two consecutive days as previously described. 13 After three cycles of ECP his cutaneous symptoms, his eruption, and his mucosal lesions were clearing. Systemic immunosuppression was gradually tapered. Complete clearance was observed after 13 cycles. After cessation of ECP, GVHD did not recur, and the patient has returned to work.
Journal of the AmericanAcademyof Dermatology May 1997 DISCUSSION
To our knowledge this is the first report of successful treatment of acute GVHD with ECP. In comparison to PUVA therapy, ECP has several advantages. ECP avoids methoxsalen plus UVA radiation of the patient's skin and may not be associated with an increased risk for the development of skin cancer. 1°-13 Recently, two patients with erythrodermic cutaneous T-cell lymphoma have been described, in whom squamous cell carcinomas developed while they were undergoing ECP. The skin cancer in these patients, however, may have resulted from factors other than ECP (e.g., previous therapy with PUVA, topical treatment with mechlorethamine, recreational habits, and the patient's age).14 PUVA treatment requires oral administration of methoxsalen three to four times per week, which, in a substantial percentage of patients (up to 20%) may cause nausea and vomiting. 15 In contrast, ECP requires oral methoxsalen administration for only 2 consecutive days at 4-week intervals; therefore psoralen-induced side effects are significantly reduced. The mechanism underlying clinical responses to ECP is not completely understood. However, PUVA is known to interact with cellular DNA, lipids, and proteins. It appears that cell surface changes, induced directly or indirectly by methoxsalen and UVA, render cells susceptible to immune surveillance and destruction. In addition, changes in antigen presentation caused by altered processing of cellular proteins or enhanced expression of class I major histocompatibility complex may also contribute. 13 Although originally developed for the treatment of cutaneous T-cell lymphoma, ECP has also been used for the management of other T-cell mediated and autoimmune diseases, including pemphigus vulgaris, rheumatoid arthritis, systemic scleroderma, systemic lupus erythematosus, and chronic GVHD. 16-2° In addition, ECP is being increasingly used together with cyclosporine or glucocorticosteroids (or both) to prevent organ rejection in patients with heart or kidney transplants. 21-~ The present observation suggests that ECP may also be used in the management of patients with acute GVHD. In view of the increasing risk of GVHD caused by the frequent use of bone marrow from unrelated donors,I, 3 it will be of interest to assess whether ECP may also be used as a prophylactic approach in bone marrow transplant recipients to prevent GVHD.
Journal of the American Academy of Dermatology Volume 36, Number 5, Part 1
Brief communications 789 13. Edelson RL, Gasparro FP. Extracorporeal photochemotherapy. In: Krutmann J, Elmets CA, editors. Photoimmunology. Oxford: Blackwell Science, 1995:23145. 14. Nehal KS, Green KB, Lim HW. Aggressive squamous cell carcinomas in patients treated with extracorporeal photopheresis for cutaneous T-cell lymphoma. Arch Dermatol 1995;131:1211-2. 15. Gschnait F. Oralphotochemotherapy. New York: Springer, 1982:18-24. t6. DaU'Amico R, Zufian F, Montini G, et al. Applications of extracorporeal photochemotherapy in "non-oncological" diseases. Int J Artif Organs 1994;16:168-72. 17. Gollnick HPM, Owsianowski M, Taube KM, et al. Unresponsive severe generalized pemphigus vulgaris successfully controlled by extracorporeal photopheresis. J Am Acad Dermatol 1993;28:122-4. 18. de Misa RF, Azana JM, Harto A, et al. Extracorporeal photochemotherapy in the treatment of severe psoriatic arthropathy. Br J Dermatol 1992;127:448. 19. Di-Spaltro FX, Cottrill C, Cahill C, et al. Extracorporeal photochemotherapy in progressive systemic sclerosis. Int J Derrnatol 1993:32:417-21. 20. Gollnick H, Owsianowski M, Siegert W, et al. Successful treatment of chronic graft-versus-host disease with extracorporeal photopheresis. Bone Marrow Transplant 1994; 14:845-8, 21. Ban- ML. Prophylactic photopheresis in cardiac transplantation. J Clin Apheresis 1994;9:228-9. 22. Dall'Amico R, Livi U, Montini A, et al. Extracorporeal photochemotherapy as adjuvant treatment on heart transplantation recipients with recurrent rejection. Transplantation In press 23. Horina JH, Mtlllegger RR, Horn S, et al. Photopheresis for renal allograft rejection [letter]. Lancet 1995;346: 6l. 24. Sunder-Plassmann G , / ) a i m / W , Knobler R, et al. Renal allograft rejection controlled by photopheresis [letter]. Lancet 1995;346:506.
REFERENCES
1. Ferrara JLM, Deeg HJ. Graft-versus-host disease. N Engl J Med 1991;324:667-74. 2. Glucksberg H, Storb R, Buckner CD, et al. Clinical manifestation of graft-versus-host disease in human recipients of marrow from HLA-matched, sibling donor. Transplantation 1974;18:459-62. 3. Storb R. Bone marrow transplantation. Transplant Proc 1995;27:2649-56. 4. Saurat J-H. Cutaneous manifestation of graft-versus-host disease. Int J Dermatol 1981;20:249-56. 5. Volc-Platzer B, Rappersberger K, Mosberger I, et al. Sequential immunohistologic analysis of skin following allogenic bone marrow transplantation. J Invest Dermatol 1988;91:162-8. 6. Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine alone for prophylaxis of acute graft-versushost disease after marrow transplantation for leukemia. N Engl J Med 1986;314:729-35. 7. Volc-Platzer B, Hoenigsmann H, Hinterberger W, et al. Photochemotherapy improves chronic cutaneous graftversus-host disease. J Am Acad Dermatol 1990;23:220-8. 8. Jampel RM, Farmer ER, Vogelsang GB, et al. PUVAtherapy for chronic cutaneous graft-versus-host disease. Arch Derrnatol 1991; 127:1673-8. 9. Deeg HJ. Photoimmunology of blood transfusion, bone marrow and organ transplantation. In: Krutmann J, Elmets CA, editors. Photoimmunology. Oxford: Blackwell Science, 1995:274-84. 10. Stern RS, Laird N, Me/ski J, et al. Cutaneous squamous cell carcinoma in patients treated with PUVA. N Engl J Med 1984;310:1156-61. 11. Stem RS, Members of the Photocbemotherapy Follow-Up Study. Genital tumors among men with psoriasis exposed to psoralen and ultraviolet A radiation (PUVA) and ultraviolet B radiation. N Engl J Med 1990;322:1093-7. 12. Altman JS, Alder SS. Development of multiple cutaneous squamous cell carcinomas during PUVA treatment for chronic graft-versus-host disease. J Am Acad Dermatol 1994;31:505-7.
Itraconazole for the treatment of tinea pedis: A dosage of 400 mg/day given for 1 week is similar in efficacy to 100 or 200 mg/day given for 2 to 4 weeks Aditya K. Gupta, MD, F R C P C , a Piet De Doncker, PhD,b Annie Heremans, MD, PhD, b Paul Stoffels, MD, b G6rald E. Pirrard, MD, PhD, c J. Decroix, MD, d M. Heenen, MD, P h D , e and Hugo Degreef, MD f Toronto, Canada, and Beerse, Likge,
Mouscron, Brussels, and Leuven, Belgium From the Department of Dermatology, University of Torontoa: the Department of Clinical Research, Janssen Research Foundation, Beerseb;the Departmentof Dermatopathology,Universityof LirgeC; Av du Parc, Mouscrond;the Department of Dermatology.Free University, B/'tlsselse; and the Department of Dermatology, Catholic University Leuven.f
Reprints are not available from the authors. J Am Acad Derrnatol 1997;36:789-92. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/97/$5.00 + 0 16/54/79668