- Email: [email protected]
Re: Complete Clinical Remission of Psoriasis 6 Months After Renal Transplantation
2074
Re: Complete Clinical Remission of Psoriasis 6 Months After Renal Transplantation C. Mele, M.P. Salerno, J. Romagnoli, C. De Simone, M. Castriota, and F. Citterio Transplant Proc 2013 Sep;45(7):2788e9 To the Editor: We were surprised to read the case report by Mele and colleagues [1] entitled “Complete clinical remission of psoriasis 6 months after renal transplantation” published in the September 2013 issue of your journal Transplantation Proceedings (Volume 45, 2788e9). In this report, Mele et al describe a 56-year-old white male with a 22-year history of severe psoriasis plus a 15- to 20-year history of presumed psoriatic arthritis. Prior therapy included topical and systemic corticosteroids plus phototherapy. The discussion, overall, focused on the novelty of psoriatic disease clearance in a patient receiving tacrolimus subsequent to his transplantation. Unfortunately, information provided regarding currently indicated therapies for psoriasis is lacking. In addition, there is no “novelty” in the finding that immunosuppression, in general or specifically from a calcineurin inhibitor, can improve a patient’s psoriasis, a known immune-mediated disease.
T
HOUGH the exact immunopathogenesis of psoriasis is unknown, T cells and various cytokines play central roles, including but not limited to Th17 cells, TNF-a, IL-23, and IL-17 [2]. Topical agents, including the calcineurin inhibitors tacrolimus and pimecrolimus [3], as well as phototherapy are used to treat patients with milder forms of disease or in combination with systemic medications. Patients with moderate-to-severe disease require systemic therapy, either oral medications or biological agents. Currently approved systemic medications for psoriasis include four oral systemic therapies: acitretin, apremilast, cyclosporine, and methotrexate, three anti-TNF-a biological therapies: etanercept, infliximab, and adalimumab, as well as ustekinumab, an anti-IL-12/23p40 monoclonal antibody, and secukinumab, an anti-IL-17A monoclonal antibody, with multiple other immunomodulatory systemic medications in the pipeline (eg, anti-IL-17 and anti-IL-23p19 agents). Two of the three currently approved oral systemic medications for psoriasis, cyclosporine and methotrexate, are known immunosuppressants and were reviewed in detail in the American Academy of Dermatology (AAD) Guidelines for the treatment of psoriasis and psoriatic arthritis [4], which Mele et al referenced in their report. Methotrexate, the most commonly prescribed traditional systemic medication for psoriasis worldwide, is used for acute graft-versus-host disease prophylaxis and has been known to improve psoriasis since the early 1960s [5]. Cyclosporine, like tacrolimus, is a calcineurin inhibitor. It forms a complex with cyclophilin, and this complex inhibits the activity of calcineurin
LETTERS TO THE EDITOR
phosphatase [6]. In 1978, cyclosporine was found to successfully prevent renal transplant rejection [7]; it was subsequently approved for use in transplant rejection by the United States Food and Drug Administration in 1983. It is currently used for renal, hepatic, and cardiac transplant rejection prophylaxis. Similarly, cyclosporine was first found to improve psoriatic skin disease in 1979 [8] and was approved for use in psoriasis in 1997. Menter and colleagues refer to cyclosporine as “one of the most effective treatments available for psoriasis” in their 2009 AAD guidelines [4]. In our experience, psoriasis patients who flare while on posttransplant (or other types of) immunosuppression are a rarity. In fact, a recent review by our group found only 3 patients in the reported literature who had severe psoriasis following transplantation which necessitated biological therapy [9]. Furthermore, it has been shown that in the absence of immunosuppression, a change in a patient’s cellular immunity via allogenic bone marrow transplantation can cure psoriasis, an observation first made in 1990 that provided substantial evidence supporting the immune component of psoriasis [10]. In summary, psoriasis is an immune-mediated disease which is currently managed by a number of therapies targeting the immune system. As such, it is expected that psoriatic patients who undergo solid organ transplantation and appropriate post-transplant immunosuppression will inevitably show some if not significant improvement in their psoriasis. Bobbak Mansouri, MDa,b,* Dario Kivelevitch, MDa a Division of Dermatology, Baylor University Medical Center Dallas, Texas, USA b Division of Dermatology, Texas A&M College of Medicine, Scott and White Hospital, Temple, TX, USA *Address correspondence to Bobbak Mansouri, MD, 409 W Adams Ave, Temple, TX, USA 76502. E-mail: bobbak. [email protected] http://dx.doi.org/10.1016/j.transproceed.2015.07.008 [1] Mele C, Salerno MP, Romagnoli J, De Simone C, Castriota M, Citterio F. Complete clinical remission of psoriasis 6 months after renal transplantation. Transplant Proc 2013;45(7): 2788e9. [2] Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361(5):496e509. [3] Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009;60(4):643e59. [4] Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009;61(3): 451e85. [5] Rees RB, Bennett JH. Methotrexate vs. aminopterin for psoriasis. Arch Dermatol 1961;83:970e2. [6] Amor KT, Ryan C, Menter A. The use of cyclosporine in dermatology: part I. J Am Acad Dermatol 2010;63(6):925e46. quiz 947e8.
LETTERS TO THE EDITOR [7] Calne RY, White DJ, Thiru S, et al. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet 1978;2(8104e5):1323e7. [8] Mueller W, Herrmann B. Cyclosporin A for psoriasis. N Engl J Med 1979;301(10):555. [9] Mansouri B, Patel M, Menter A. Tumour necrosis factoralpha inhibitor use in patients with psoriasis with organ transplantation. Br J Dermatol 2013;169(2):481e3. [10] Eedy DJ, Burrows D, Bridges JM, Jones FG. Clearance of severe psoriasis after allogenic bone marrow transplantation. BMJ 1990;300(6729):908.
Response The letter of B. Mansouri and D. Kivelevitch alleges as moot our case report on a patient with severe psoriasis, that disappeared after renal transplantation under tacrolimus immunosuppression. [Transplantation Proceedings, 45,2788e9 (2013)]. A recent report describes the importance of patient perspective management of psoriasis. A population-based multinational survey of psoriasis and psoriatic arthritis patients showed that over 80% of subjects displayed involvement of 4 palms body surface area and that 59% of psoriatic arthritis patients were receiving no treatment or topical treatment only. Among the patients who had received oral or biologic therapy, 57% and 45%, respectively, discontinued therapy most often due to safety/tolerability reasons or a lack/loss of efficacy [1]. These data indicate that the treatment of psoriasis remains complex, must be personalized, should be accepted by the patient, and possibly carry a low incidence of side effects.
T
HE patient described in our report had a 22-year history of severe psoriasis plus a 15 to 20-year history of psoriatic arthritis. Previous therapy included topical and systemic corticosteroids plus phototherapy. Cyclosporine was not a therapeutic option because of declining renal function. Once on dialysis systemic immunosuppression was again not an option, because we believe that a dialysis patient should not accept the risk of systemic immunosuppression. At the time of renal transplantation we initiated immunosuppression with tacrolimus (0.1 mg/kg); in less than 1 month our patient displayed both good renal function and remission of his long lasting severe psoriasis. The therapeutic value of tacrolimus in psoriasis was discovered by accident when four organ transplant recipients were treated with tacrolimus to prevent graft rejection, experiencing significant improvements in their recalcitrant psoriasis. A subsequent 9-week, randomized, placebo-controlled trial of 50 non-transplant patients with moderate to severe psoriasis showed that oral tacrolimus (0.05 to 0.15 mg/kg/d) reduced PASI scores by 83% compared with 47% for placebo treated subjects [2]. In the 2009 guidelines of care for the management of psoriasis and psoriatic arthritis, cited by Mansouri and Kivelevitch, systemic tacrolimus was not suggested as a treatment option, because “although there are placebo-controlled trials evaluating the use of tacrolimus in the treatment of psoriasis
2075
requiring systemic therapy, the quality of the evidences supporting its use is not very convincing” [3]. So the efficacy of systemic use of tacrolimus in the treatment of severe psoriasis is still an open question. There are no guidelines concerning management of a patient with severe psoriasis on hemodialysis at the time of transplantation. For this reason we thought that it was worthwhile to share our off label experience with tacrolimus with the transplant community. We agree with the comment of Mansouri and Kivelevitch that it is expected that psoriatic patients who undergo solid organ transplantation and receive appropriate posttransplant immunosuppression will inevitably show significant improvement in their psoriasis; but expecting a result and showing evidence of it are different. A new clinical trial evaluating the benefit of systemic administration with tacrolimus in transplant patients affected by severe psoriasis could resolve the issue, as would a study employing other expensive biological immunosuppressive agents [4]. Prof. Franco Citterio Istituto di Clinica Chirurgica Renal Transplantation Unit Department of Surgical Science Università Cattolica del Sacro Cuore Largo F. Vito 1 00168, Roma E-mail: [email protected] http://dx.doi.org/10.1016/j.transproceed.2015.07.009 [1] Lebwohl MG, Bachelez H, Barker J, et al. Patient perspectives in the management of psoriasis: Results from the populationbased Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol 2013;5(70):871. [2] Bos JD, Witkamp L, Zonnevald IM. Systemic tacrolimus (FK 506) is effective for the treatment of psoriasis in a double-blind, placebo-controlled study: the European FK 506 multicenter psoriasis study group. Arch Dermatol 1996;132:419e23. [3] Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009;61:451e85. [4] Mansouri B, Patel M, Menter A. Tumour necrosis factoralpha inhibitor use in patients with psoriasis with organ transplantation. Br J Dermatol 2013;169(2):481e3.
Heart Transplantation for End-Stage Heart Failure Due to Cardiac Sarcoidosis D. Perkel, L.S.C. Czer, R.P. Morrissey, A. Ruzza, M. Rafiei, M. Awad, J. Patel, and J.A. Kobashigawa Transplant Proc 2013;45(6):2384e6 To the Editor: We read with keen clinical interest the article by Perkel et al entitled “Heart Transplantation for End-Stage Heart Failure Due to Cardiac Sarcoidosis,”
Re: Complete Clinical Remission of Psoriasis 6 Months After Renal Transplantation C. Mele, M.P. Salerno, J. Romagnoli, C. De Simone, M. Castriota, and F. Citterio Transplant Proc 2013 Sep;45(7):2788e9 To the Editor: We were surprised to read the case report by Mele and colleagues [1] entitled “Complete clinical remission of psoriasis 6 months after renal transplantation” published in the September 2013 issue of your journal Transplantation Proceedings (Volume 45, 2788e9). In this report, Mele et al describe a 56-year-old white male with a 22-year history of severe psoriasis plus a 15- to 20-year history of presumed psoriatic arthritis. Prior therapy included topical and systemic corticosteroids plus phototherapy. The discussion, overall, focused on the novelty of psoriatic disease clearance in a patient receiving tacrolimus subsequent to his transplantation. Unfortunately, information provided regarding currently indicated therapies for psoriasis is lacking. In addition, there is no “novelty” in the finding that immunosuppression, in general or specifically from a calcineurin inhibitor, can improve a patient’s psoriasis, a known immune-mediated disease.
T
HOUGH the exact immunopathogenesis of psoriasis is unknown, T cells and various cytokines play central roles, including but not limited to Th17 cells, TNF-a, IL-23, and IL-17 [2]. Topical agents, including the calcineurin inhibitors tacrolimus and pimecrolimus [3], as well as phototherapy are used to treat patients with milder forms of disease or in combination with systemic medications. Patients with moderate-to-severe disease require systemic therapy, either oral medications or biological agents. Currently approved systemic medications for psoriasis include four oral systemic therapies: acitretin, apremilast, cyclosporine, and methotrexate, three anti-TNF-a biological therapies: etanercept, infliximab, and adalimumab, as well as ustekinumab, an anti-IL-12/23p40 monoclonal antibody, and secukinumab, an anti-IL-17A monoclonal antibody, with multiple other immunomodulatory systemic medications in the pipeline (eg, anti-IL-17 and anti-IL-23p19 agents). Two of the three currently approved oral systemic medications for psoriasis, cyclosporine and methotrexate, are known immunosuppressants and were reviewed in detail in the American Academy of Dermatology (AAD) Guidelines for the treatment of psoriasis and psoriatic arthritis [4], which Mele et al referenced in their report. Methotrexate, the most commonly prescribed traditional systemic medication for psoriasis worldwide, is used for acute graft-versus-host disease prophylaxis and has been known to improve psoriasis since the early 1960s [5]. Cyclosporine, like tacrolimus, is a calcineurin inhibitor. It forms a complex with cyclophilin, and this complex inhibits the activity of calcineurin
LETTERS TO THE EDITOR
phosphatase [6]. In 1978, cyclosporine was found to successfully prevent renal transplant rejection [7]; it was subsequently approved for use in transplant rejection by the United States Food and Drug Administration in 1983. It is currently used for renal, hepatic, and cardiac transplant rejection prophylaxis. Similarly, cyclosporine was first found to improve psoriatic skin disease in 1979 [8] and was approved for use in psoriasis in 1997. Menter and colleagues refer to cyclosporine as “one of the most effective treatments available for psoriasis” in their 2009 AAD guidelines [4]. In our experience, psoriasis patients who flare while on posttransplant (or other types of) immunosuppression are a rarity. In fact, a recent review by our group found only 3 patients in the reported literature who had severe psoriasis following transplantation which necessitated biological therapy [9]. Furthermore, it has been shown that in the absence of immunosuppression, a change in a patient’s cellular immunity via allogenic bone marrow transplantation can cure psoriasis, an observation first made in 1990 that provided substantial evidence supporting the immune component of psoriasis [10]. In summary, psoriasis is an immune-mediated disease which is currently managed by a number of therapies targeting the immune system. As such, it is expected that psoriatic patients who undergo solid organ transplantation and appropriate post-transplant immunosuppression will inevitably show some if not significant improvement in their psoriasis. Bobbak Mansouri, MDa,b,* Dario Kivelevitch, MDa a Division of Dermatology, Baylor University Medical Center Dallas, Texas, USA b Division of Dermatology, Texas A&M College of Medicine, Scott and White Hospital, Temple, TX, USA *Address correspondence to Bobbak Mansouri, MD, 409 W Adams Ave, Temple, TX, USA 76502. E-mail: bobbak. [email protected] http://dx.doi.org/10.1016/j.transproceed.2015.07.008 [1] Mele C, Salerno MP, Romagnoli J, De Simone C, Castriota M, Citterio F. Complete clinical remission of psoriasis 6 months after renal transplantation. Transplant Proc 2013;45(7): 2788e9. [2] Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med 2009;361(5):496e509. [3] Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009;60(4):643e59. [4] Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009;61(3): 451e85. [5] Rees RB, Bennett JH. Methotrexate vs. aminopterin for psoriasis. Arch Dermatol 1961;83:970e2. [6] Amor KT, Ryan C, Menter A. The use of cyclosporine in dermatology: part I. J Am Acad Dermatol 2010;63(6):925e46. quiz 947e8.
LETTERS TO THE EDITOR [7] Calne RY, White DJ, Thiru S, et al. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet 1978;2(8104e5):1323e7. [8] Mueller W, Herrmann B. Cyclosporin A for psoriasis. N Engl J Med 1979;301(10):555. [9] Mansouri B, Patel M, Menter A. Tumour necrosis factoralpha inhibitor use in patients with psoriasis with organ transplantation. Br J Dermatol 2013;169(2):481e3. [10] Eedy DJ, Burrows D, Bridges JM, Jones FG. Clearance of severe psoriasis after allogenic bone marrow transplantation. BMJ 1990;300(6729):908.
Response The letter of B. Mansouri and D. Kivelevitch alleges as moot our case report on a patient with severe psoriasis, that disappeared after renal transplantation under tacrolimus immunosuppression. [Transplantation Proceedings, 45,2788e9 (2013)]. A recent report describes the importance of patient perspective management of psoriasis. A population-based multinational survey of psoriasis and psoriatic arthritis patients showed that over 80% of subjects displayed involvement of 4 palms body surface area and that 59% of psoriatic arthritis patients were receiving no treatment or topical treatment only. Among the patients who had received oral or biologic therapy, 57% and 45%, respectively, discontinued therapy most often due to safety/tolerability reasons or a lack/loss of efficacy [1]. These data indicate that the treatment of psoriasis remains complex, must be personalized, should be accepted by the patient, and possibly carry a low incidence of side effects.
T
HE patient described in our report had a 22-year history of severe psoriasis plus a 15 to 20-year history of psoriatic arthritis. Previous therapy included topical and systemic corticosteroids plus phototherapy. Cyclosporine was not a therapeutic option because of declining renal function. Once on dialysis systemic immunosuppression was again not an option, because we believe that a dialysis patient should not accept the risk of systemic immunosuppression. At the time of renal transplantation we initiated immunosuppression with tacrolimus (0.1 mg/kg); in less than 1 month our patient displayed both good renal function and remission of his long lasting severe psoriasis. The therapeutic value of tacrolimus in psoriasis was discovered by accident when four organ transplant recipients were treated with tacrolimus to prevent graft rejection, experiencing significant improvements in their recalcitrant psoriasis. A subsequent 9-week, randomized, placebo-controlled trial of 50 non-transplant patients with moderate to severe psoriasis showed that oral tacrolimus (0.05 to 0.15 mg/kg/d) reduced PASI scores by 83% compared with 47% for placebo treated subjects [2]. In the 2009 guidelines of care for the management of psoriasis and psoriatic arthritis, cited by Mansouri and Kivelevitch, systemic tacrolimus was not suggested as a treatment option, because “although there are placebo-controlled trials evaluating the use of tacrolimus in the treatment of psoriasis
2075
requiring systemic therapy, the quality of the evidences supporting its use is not very convincing” [3]. So the efficacy of systemic use of tacrolimus in the treatment of severe psoriasis is still an open question. There are no guidelines concerning management of a patient with severe psoriasis on hemodialysis at the time of transplantation. For this reason we thought that it was worthwhile to share our off label experience with tacrolimus with the transplant community. We agree with the comment of Mansouri and Kivelevitch that it is expected that psoriatic patients who undergo solid organ transplantation and receive appropriate posttransplant immunosuppression will inevitably show significant improvement in their psoriasis; but expecting a result and showing evidence of it are different. A new clinical trial evaluating the benefit of systemic administration with tacrolimus in transplant patients affected by severe psoriasis could resolve the issue, as would a study employing other expensive biological immunosuppressive agents [4]. Prof. Franco Citterio Istituto di Clinica Chirurgica Renal Transplantation Unit Department of Surgical Science Università Cattolica del Sacro Cuore Largo F. Vito 1 00168, Roma E-mail: [email protected] http://dx.doi.org/10.1016/j.transproceed.2015.07.009 [1] Lebwohl MG, Bachelez H, Barker J, et al. Patient perspectives in the management of psoriasis: Results from the populationbased Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol 2013;5(70):871. [2] Bos JD, Witkamp L, Zonnevald IM. Systemic tacrolimus (FK 506) is effective for the treatment of psoriasis in a double-blind, placebo-controlled study: the European FK 506 multicenter psoriasis study group. Arch Dermatol 1996;132:419e23. [3] Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009;61:451e85. [4] Mansouri B, Patel M, Menter A. Tumour necrosis factoralpha inhibitor use in patients with psoriasis with organ transplantation. Br J Dermatol 2013;169(2):481e3.
Heart Transplantation for End-Stage Heart Failure Due to Cardiac Sarcoidosis D. Perkel, L.S.C. Czer, R.P. Morrissey, A. Ruzza, M. Rafiei, M. Awad, J. Patel, and J.A. Kobashigawa Transplant Proc 2013;45(6):2384e6 To the Editor: We read with keen clinical interest the article by Perkel et al entitled “Heart Transplantation for End-Stage Heart Failure Due to Cardiac Sarcoidosis,”