Journal of the American Academy of Dermatology
Volume 61, Issue 3 , Pages 451-485 , September 2009

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

  • Alan Menter, MD (Chair)

      Affiliations

    • Baylor University Medical Center, Dallas, Texas
    • ,
  • Neil J. Korman, MD, PhD

      Affiliations

    • Murdough Family Center For Psoriasis, Department of Dermatology, University Hospitals Case Medical Center, Cleveland, Ohio
    • ,
  • Craig A. Elmets, MD

      Affiliations

    • Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
    • ,
  • Steven R. Feldman, MD, PhD

      Affiliations

    • Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
    • ,
  • Joel M. Gelfand, MD, MSCE

      Affiliations

    • Department of Dermatology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania
    • ,
  • Kenneth B. Gordon, MD

      Affiliations

    • Division of Dermatology, Evanston Northwestern Healthcare and Department of Dermatology, Northwestern University, Fienberg School of Medicine, Chicago, Illinois
    • ,
  • Alice B. Gottlieb, MD, PhD

      Affiliations

    • Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
    • ,
  • John Y.M. Koo, MD

      Affiliations

    • Department of Dermatology, University of California–San Francisco, San Francisco, California
    • ,
  • Mark Lebwohl, MD

      Affiliations

    • Department of Dermatology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Henry W. Lim, MD

      Affiliations

    • Department of Dermatology, Henry Ford Hospital, Detroit, Michigan
    • ,
  • Abby S. Van Voorhees, MD

      Affiliations

    • Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania
    • ,
  • Karl R. Beutner, MD, PhD

      Affiliations

    • Anacor Pharmaceuticals Inc, Palo Alto, CA, Department of Dermatology, University of California, San Francisco, California
    • ,
  • Reva Bhushan, PhD

      Affiliations

    • American Academy of Dermatology, Schaumburg, Illinois
    • Corresponding Author InformationReprint requests: Reva Bhushan, PhD, 930 E Woodfield Rd, Schaumburg, IL 60173.

References 

  1. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis, section 1: overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826–850
  2. Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis, section 2: psoriatic arthritis; overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58:851–864
  3. Ebell MH, Siwek J, Weiss BD, Woolf SH, Susman JL, Ewigman B, et al. Simplifying the language of evidence to improve patient care: Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in medical literature. J Fam Pract. 2004;53:111–120
  4. Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation consensus conference. J Am Acad Dermatol. 2009;60:824–837
  5. Ritchlin CT, Kavanaugh A, Gladman DD, Mease PJ, Helliwell P, Boehncke WH, et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis doi:10.1136/ard.2008.094946. Published online October 24, 2008.
  6. Warren RB, Chalmers RJ, Griffiths CE, Menter A. Methotrexate for psoriasis in the era of biological therapy. Clin Exp Dermatol. 2008;33:551–554
  7. Atzeni F, Sarzi-Puttini P. Autoantibody production in patients treated with anti-TNF. Expert Rev Clin Immunol. 2008;4:275–280
  8. Lebwohl M, Ellis C, Gottlieb A, Koo J, Krueger G, Linden K, et al. Cyclosporine consensus conference: with emphasis on the treatment of psoriasis. J Am Acad Dermatol. 1998;39:464–475
  9. Lowe NJ, Wieder JM, Rosenbach A, Johnson K, Kunkel R, Bainbridge C, et al. Long-term low-dose cyclosporine therapy for severe psoriasis: effects on renal function and structure. J Am Acad Dermatol. 1996;35:710–719
  10. Griffiths CE, Dubertret L, Ellis CN, Finlay AY, Finzi AF, Ho VC, et al. Cyclosporin in psoriasis clinical practice: an international consensus statement. Br J Dermatol. 2004;150(Suppl):11–23
  11. Carey W, Glazer S, Gottlieb AB, Lebwohl M, Leonardi C, Menter A, et al. Relapse, rebound, and psoriasis adverse events: an advisory group report. J Am Acad Dermatol. 2006;54(Suppl):S171–S181
  12. White SI, Marks JM, Shuster S. Etretinate in pustular psoriasis of palms and soles. Br J Dermatol. 1985;113:581–585
  13. Menter MA, See JA, Amend WJ, Ellis CN, Krueger GG, Lebwohl M, et al. Proceedings of the Psoriasis Combination and Rotation Therapy Conference; Deer Valley, UT; October 7-9, 1994. J Am Acad Dermatol. 1996;34:315–321
  14. Weinstein GD, Frost P. Methotrexate for psoriasis: a new therapeutic schedule. Arch Dermatol. 1971;103:33–38
  15. Jeffes EW, McCullough JL, Pittelkow MR, McCormick A, Almanzor J, Liu G, et al. Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate. J Invest Dermatol. 1995;104:183–188
  16. Saporito FC, Menter MA. Methotrexate and psoriasis in the era of new biologic agents. J Am Acad Dermatol. 2004;50:301–309
  17. Roenigk HH, Maibach HI, Weinstein GD. Use of methotrexate in psoriasis. Arch Dermatol. 1972;105:363–365
  18. Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003;349:658–665
  19. Flytstrom I, Stenberg B, Svensson A, Bergbrant IM. Methotrexate vs cyclosporin in psoriasis: effectiveness, quality of life and safety. a randomized controlled trial. Br J Dermatol. 2008;158:116–121
  20. Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs methotrexate vs placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008;158:558–566
  21. Strober BE, Menon K. Folate supplementation during methotrexate therapy for patients with psoriasis. J Am Acad Dermatol. 2005;53:652–659
  22. Salim A, Tan E, Ilchyshyn A, Berth-Jones J. Folic acid supplementation during treatment of psoriasis with methotrexate: a randomized, double-blind, placebo-controlled trial. Br J Dermatol. 2006;154:1169–1174
  23. Brownell I, Strober BE. Folate with methotrexate: big benefit, questionable cost. Br J Dermatol. 2007;157:213
  24. MacDonald A, Burden AD. Noninvasive monitoring for methotrexate hepatotoxicity. Br J Dermatol. 2005;152:405–408
  25. Belzunegui J, Intxausti JJ, De Dios JR, Lopez-Dominguez L, Queiro R, Gonzalez C, et al. Absence of pulmonary fibrosis in patients with psoriatic arthritis treated with weekly low-dose methotrexate. Clin Exp Rheumatol. 2001;19:727–730
  26. Kremer JM. Toward a better understanding of methotrexate. Arthritis Rheum. 2004;50:1370–1382
  27. Helliwell PS, Taylor WJ. Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs–comparison of drugs and adverse reactions. J Rheumatol. 2008;35:472–476
  28. Binymin K, Cooper RG. Late reactivation of spinal tuberculosis by low-dose methotrexate therapy in a patient with rheumatoid arthritis. Rheumatology (Oxford). 2001;40:341–342
  29. Clarke LE, Junkins-Hopkins J, Seykora JT, Adler DJ, Elenitsas R. Methotrexate-associated lymphoproliferative disorder in a patient with rheumatoid arthritis presenting in the skin. J Am Acad Dermatol. 2007;56:686–690
  30. Gwak GY, Koh KC, Kim HY. Fatal hepatic failure associated with hepatitis B virus reactivation in a hepatitis B surface antigen-negative patient with rheumatoid arthritis receiving low dose methotrexate. Clin Exp Rheumatol. 2007;25:888–889
  31. Maruani A, Wierzbicka E, Machet MC, Abdallah-Lotf M, de Muret A, Machet L. Reversal of multifocal cutaneous lymphoproliferative disease associated with Epstein-Barr virus after withdrawal of methotrexate therapy for rheumatoid arthritis. J Am Acad Dermatol. 2007;57(Suppl):S69–S71
  32. Gutierrez-Urena S, Molina JF, Garcia CO, Cuellar ML, Espinoza LR. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. Arthritis Rheum. 1996;39:272–276
  33. Cohen PR, Schulze KE, Nelson BR. Pancytopenia after a single intradermal infiltration of methotrexate. J Drugs Dermatol. 2005;4:648–651
  34. Jih DM, Werth VP. Thrombocytopenia after a single test dose of methotrexate. J Am Acad Dermatol. 1998;39:349–351
  35. Preet Singh Y, Aggarwal A, Misra R, Agarwal V. Low-dose methotrexate-induced pancytopenia. Clin Rheumatol. 2007;26:84–87
  36. Yang CP, Kuo MC, Guh JY, Chen HC. Pancytopenia after low dose methotrexate therapy in a hemodialysis patient: case report and review of literature. Ren Fail. 2006;28:95–97
  37. Berends MA, Snoek J, de Jong EM, van de Kerkhof PC, van Oijen MG, van Krieken JH, et al. Liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent. Aliment Pharmacol Ther. 2006;24:805–811
  38. Zachariae H. Liver biopsies and methotrexate: a time for reconsideration?. J Am Acad Dermatol. 2000;42:531–534
  39. Langman G, Hall PM, Todd G. Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol. 2001;16:1395–1401
  40. Rosenberg P, Urwitz H, Johannesson A, Ros AM, Lindholm J, Kinnman N, et al. Psoriasis patients with diabetes type 2 are at high risk of developing liver fibrosis during methotrexate treatment. J Hepatol. 2007;46:1111–1118
  41. Kent PD, Luthra HS, Michet C. Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients with rheumatoid arthritis. J Rheumatol. 2004;31:1727–1731
  42. Erickson AR, Reddy V, Vogelgesang SA, West SG. Usefulness of the American College of Rheumatology recommendations for liver biopsy in methotrexate-treated rheumatoid arthritis patients. Arthritis Rheum. 1995;38:1115–1119
  43. Aithal GP, Haugk B, Das S, Card T, Burt AD, Record CO. Monitoring methotrexate-induced hepatic fibrosis in patients with psoriasis: are serial liver biopsies justified?. Aliment Pharmacol Ther. 2004;19:391–399
  44. Thomas JA, Aithal GP. Monitoring liver function during methotrexate therapy for psoriasis: are routine biopsies really necessary?. Am J Clin Dermatol. 2005;6:357–363
  45. Chalmers RJ, Kirby B, Smith A, Burrows P, Little R, Horan M, et al. Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicenter audit and health economic analysis. Br J Dermatol. 2005;152:444–450
  46. Sagir A, Erhardt A, Schmitt M, Haussinger D. Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. Hepatology. 2008;47:592–595
  47. Guha IN, Parkes J, Roderick P, Chattopadhyay D, Cross R, Harris S, et al. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: validating the European liver fibrosis panel and exploring simple markers. Hepatology. 2008;47:455–460
  48. Lloyd ME, Carr M, McElhatton P, Hall GM, Hughes RA. The effects of methotrexate on pregnancy, fertility and lactation. QJM. 1999;92:551–563
  49. Aviles A, Diaz-Maqueo JC, Talavera A, Guzman R, Garcia EL. Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol. 1991;36:243–248
  50. Heetun ZS, Byrnes C, Neary P, O'Morain C. Review article: reproduction in the patient with inflammatory bowel disease. Aliment Pharmacol Ther. 2007;26:513–533
  51. Saxena AK, Dhungel S, Bhattacharya S, Jha CB, Srivastava AK. Effect of chronic low dose of methotrexate on cellular proliferation during spermatogenesis in rats. Arch Androl. 2004;50:33–35
  52. Morris LF, Harrod MJ, Menter MA, Silverman AK. Methotrexate and reproduction in men: case report and recommendations. J Am Acad Dermatol. 1993;29:913–916
  53. Sussman A, Leonard JM. Psoriasis, methotrexate, and oligospermia. Arch Dermatol. 1980;116:215–217
  54. El-Beheiry A, El-Mansy E, Kamel N, Salama N. Methotrexate and fertility in men. Arch Androl. 1979;3:177–179
  55. Estop AM, Cieply K, Van Kirk V, Levinson F, Buckingham R. Sperm chromosome studies in patients taking low dose methotrexate. Am J Hum Genet. 1992;51:A314
  56. Kumar B, Dhar S, Handa S, Kaur I. Methotrexate in childhood psoriasis. Pediatr Dermatol. 1994;11:271–273
  57. Dadlani C, Orlow SJ. Treatment of children and adolescents with methotrexate, cyclosporine, and etanercept: review of the dermatologic and rheumatologic literature. J Am Acad Dermatol. 2005;52:316–340
  58. Tracy TS, Krohn K, Jones DR, Bradley JD, Hall SD, Brater DC. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol. 1992;42:121–125
  59. Tracy TS, Worster T, Bradley JD, Greene PK, Brater DC. Methotrexate disposition following concomitant administration of ketoprofen, piroxicam and flurbiprofen in patients with rheumatoid arthritis. Br J Clin Pharmacol. 1994;37:453–456
  60. Turck D, Roth W, Busch U. A review of the clinical pharmacokinetics of meloxicam. Br J Rheumatol. 1996;35(Suppl):13–16
  61. Hartmann SN, Rordorf CM, Milosavljev S, Branson JM, Chales GH, Juvin RR, et al. Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients. Ann Pharmacother. 2004;38:1582–1587
  62. Karim A, Tolbert DS, Hunt TL, Hubbard RC, Harper KM, Geis GS. Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol. 1999;26:2539–2543
  63. Schwartz JI, Agrawal NG, Wong PH, Bachmann KA, Porras AG, Miller JL, et al. Lack of pharmacokinetic interaction between rofecoxib and methotrexate in rheumatoid arthritis patients. J Clin Pharmacol. 2001;41:1120–1130
  64. Cohn DL, O'Brien RJ, Geiter LJ, Gordin FM, Hershfield E, Horsburgh RC, et al. Targeted tuberculin testing and treatment of latent tuberculosis infection: Centers for Disease Control and Prevention 2000. Available from: URL: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm. Accessed April 21, 2009.
  65. Doherty SD, Van Voorhees A, Lebwohl MG, Korman NJ, Young MS, Hsu S, et al. National Psoriasis Foundation consensus statement on screening for latent tuberculosis infection in patients with psoriasis treated with systemic and biologic agents. J Am Acad Dermatol. 2008;59:209–217
  66. Department of Health and Human Services (HHS) and the Department of Agriculture (USDA). Nutrition and your health: dietary guidelines for Americans. Washington (DC): US Department of Agriculture; 2000. Available at: http://www.health.gov/DietaryGuidelines/dga2005/document/default.htm. Accessed April 21, 2009.
  67. Lowenthal KE, Horn PJ, Kalb RE. Concurrent use of methotrexate and acitretin revisited. J Dermatolog Treat. 2008;19:22–26
  68. Mueller W, Herrmann B. Cyclosporin A for psoriasis. N Engl J Med. 1979;301:555
  69. Gottlieb AB, Grossman RM, Khandke L, Carter DM, Sehgal PB, Fu SM, et al. Studies of the effect of cyclosporine in psoriasis in vivo: combined effects on activated T lymphocytes and epidermal regenerative maturation. J Invest Dermatol. 1992;98:302–309
  70. Prens EP, van Joost T, Hegmans JP. ′tHooft-Benne K, Ysselmuiden OE, Benner R. Effects of cyclosporine on cytokines and cytokine receptors in psoriasis. J Am Acad Dermatol. 1995;33:947–953
  71. Berth-Jones J, Henderson CA, Munro CS, Rogers S, Chalmers RJ, Boffa MJ, et al. Treatment of psoriasis with intermittent short course cyclosporin (Neoral): a multicenter study. Br J Dermatol. 1997;136:527–530
  72. Ellis CN, Fradin MS, Messana JM, Brown MD, Siegel MT, Hartley AH, et al. Cyclosporine for plaque-type psoriasis: results of a multidose, double-blind trial. N Engl J Med. 1991;324:277–284
  73. Faerber L, Braeutigam M, Weidinger G, Mrowietz U, Christophers E, Schulze HJ, et al. Cyclosporine in severe psoriasis: results of a meta-analysis in 579 patients. Am J Clin Dermatol. 2001;2:41–47
  74. Ho VC, Griffiths CE, Albrecht G, Vanaclocha F, Leon-Dorantes G, Atakan N, et al. Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicenter, randomized study. the PISCES study group. Br J Dermatol. 1999;141:283–291
  75. Ho VC, Griffiths CE, Berth-Jones J, Papp KA, Vanaclocha F, Dauden E, et al. Intermittent short courses of cyclosporine microemulsion for the long-term management of psoriasis: a 2-year cohort study. J Am Acad Dermatol. 2001;44:643–651
  76. Nast A, Kopp I, Augustin M, Banditt KB, Boehncke WH, Follmann M, et al. German evidence-based guidelines for the treatment of psoriasis vulgaris (short version). Arch Dermatol Res. 2007;299:111–138
  77. Mrowietz U, Farber L, Henneicke-von Zepelin HH, Bachmann H, Welzel D, Christophers E. Long-term maintenance therapy with cyclosporine and posttreatment survey in severe psoriasis: results of a multicenter study; German multicenter study. J Am Acad Dermatol. 1995;33:470–475
  78. Shupack J, Abel E, Bauer E, Brown M, Drake L, Freinkel R, et al. Cyclosporine as maintenance therapy in patients with severe psoriasis. J Am Acad Dermatol. 1997;36:423–432
  79. Food and Drug Administration (FDA). Cyclosporin FDA package insert. Available from: URL: http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.Overview&DrugName=CYCLOSPORINE. Accessed January 9, 2009.
  80. Taler SJ, Textor SC, Canzanello VJ, Schwartz L. Cyclosporin-induced hypertension: incidence, pathogenesis and management. Drug Saf. 1999;20:437–449
  81. Zachariae H, Kragballe K, Hansen HE, Marcussen N, Olsen S. Renal biopsy findings in long-term cyclosporin treatment of psoriasis. Br J Dermatol. 1997;136:531–535
  82. Marcil I, Stern RS. Squamous-cell cancer of the skin in patients given PUVA and cyclosporin: nested cohort crossover study. Lancet. 2001;358:1042–1045
  83. Paul CF, Ho VC, McGeown C, Christophers E, Schmidtmann B, Guillaume JC, et al. Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 year cohort study. J Invest Dermatol. 2003;120:211–216
  84. Gilbert SC, Emmett M, Menter A, Silverman A, Klintmalm G. Cyclosporine therapy for psoriasis: serum creatinine measurements are an unreliable predictor of decreased renal function. J Am Acad Dermatol. 1989;21:470–474
  85. Neoral [package insert] . East. Hanover, NJ: Novartis PC; 2005;
  86. Markham T, Watson A, Rogers S. Adverse effects with long-term cyclosporin for severe psoriasis. Clin Exp Dermatol. 2002;27:111–114
  87. Powles AV, Hardman CM, Porter WM, Cook T, Hulme B, Fry L. Renal function after 10 years' treatment with cyclosporin for psoriasis. Br J Dermatol. 1998;138:443–449
  88. Deray G, Baumelou B, Le Hoang P, Aupetit B, Girard B, Baumelou A, et al. Enhancement of cyclosporin nephrotoxicity by diuretic therapy. Clin Nephrol. 1989;32:47
  89. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560–2572
  90. Silverman AK, Emmett M, Menter A. Can maintenance cyclosporine be used in psoriasis without decreasing renal function?. Semin Dermatol. 1992;11:302–312
  91. Berth-Jones J. The use of cyclosporin in psoriasis. J Dermatolog Treat. 2005;16:258–277
  92. Christopher V, Al-Chalabi T, Richardson PD, Muiesan P, Rela M, Heaton ND, et al. Pregnancy outcome after liver transplantation: a single-center experience of 71 pregnancies in 45 recipients. Liver Transpl. 2006;12:1138–1143
  93. Ostensen M, Lockshin M, Doria A, Valesini G, Meroni P, Gordon C, et al. Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs. Rheumatology (Oxford). 2008;47(Suppl):iii28–31
  94. Ghafari A, Sanadgol H. Pregnancy after renal transplantation: ten-year single-center experience. Transplant Proc. 2008;40:251–252
  95. Tendron-Franzin A, Gouyon JB, Guignard JP, Decramer S, Justrabo E, Gilbert T, et al. Long-term effects of in utero exposure to cyclosporin A on renal function in the rabbit. J Am Soc Nephrol. 2004;15:2687–2693
  96. Cochat P, Decramer S, Robert-Gnansia E, Dubourg L, Audra P. Renal outcome of children exposed to cyclosporine in utero. Transplant Proc. 2004;36:208–210S
  97. Bar Oz B, Hackman R, Einarson T, Koren G. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation. 2001;71:1051–1055
  98. Kilic SS, Hacimustafaoglu M, Celebi S, Karadeniz A, Ildirim I. Low dose cyclosporin A treatment in generalized pustular psoriasis. Pediatr Dermatol. 2001;18:246–248
  99. Mahe E, Bodemer C, Pruszkowski A, Teillac-Hamel D, de Prost Y. Cyclosporine in childhood psoriasis. Arch Dermatol. 2001;137:1532–1533
  100. Perrett CM, Ilchyshyn A, Berth-Jones J. Cyclosporin in childhood psoriasis. J Dermatolog Treat. 2003;14:113–118
  101. Paul MD, Parfrey PS, Smart M, Gault H. The effect of ethanol on serum cyclosporine A levels in renal transplant recipients. Am J Kidney Dis. 1987;10:133–135
  102. Omar MA, Wilson JP, Cox TS. Rhabdomyolysis and HMG-CoA reductase inhibitors. Ann Pharmacother. 2001;35:1096–1107
  103. Heydendael VM, Spuls PI, Ten Berge IJ, Opmeer BC, Bos JD, de Rie MA. Cyclosporin trough levels: is monitoring necessary during short-term treatment in psoriasis? A systematic review and clinical data on trough levels. Br J Dermatol. 2002;147:122–129
  104. Grekas D, Alivanis P, Kiriazopoulou V, Dioudis C, Sioulis A, Derveniotis V, et al. Influenza vaccination on renal transplant patients is safe and serologically effective. Int J Clin Pharmacol Ther Toxicol. 1993;31:553–556
  105. Soesman NM, Rimmelzwaan GF, Nieuwkoop NJ, Beyer WE, Tilanus HW, Kemmeren MH, et al. Efficacy of influenza vaccination in adult liver transplant recipients. J Med Virol. 2000;61:85–93
  106. Versluis DJ, Beyer WE, Masurel N, Wenting GJ, Weimar W. Impairment of the immune response to influenza vaccination in renal transplant recipients by cyclosporine, but not azathioprine. Transplantation. 1986;42:376–379
  107. Geiger JM, Czarnetzki BM. Acitretin (Ro 10-1670, etretin): overall evaluation of clinical studies. Dermatologica. 1988;176:182–190
  108. Goldfarb MT, Ellis CN, Gupta AK, Tincoff T, Hamilton TA, Voorhees JJ. Acitretin improves psoriasis in a dose-dependent fashion. J Am Acad Dermatol. 1988;18:655–662
  109. Lassus A, Geiger JM, Nyblom M, Virrankoski T, Kaartamaa M, Ingervo L. Treatment of severe psoriasis with etretin (RO 10-1670). Br J Dermatol. 1987;117:333–341
  110. Ling MR. Acitretin: optimal dosing strategies. J Am Acad Dermatol. 1999;41(Suppl):S13–S17
  111. Lowe NJ, Lazarus V, Matt L. Systemic retinoid therapy for psoriasis. J Am Acad Dermatol. 1988;19:186–191
  112. Murray HE, Anhalt AW, Lessard R, Schacter RK, Ross JB, Stewart WD, et al. A 12-month treatment of severe psoriasis with acitretin: results of a Canadian open multicenter study. J Am Acad Dermatol. 1991;24:598–602
  113. Olsen EA, Weed WW, Meyer CJ, Cobo LM. A double-blind, placebo-controlled trial of acitretin for the treatment of psoriasis. J Am Acad Dermatol. 1989;21:681–686
  114. Torok L, Kadar L, Geiger JM. Acitretin treatment of severe psoriasis. Acta Derm Venereol Suppl (Stockh). 1989;146:104–106
  115. Gollnick H, Bauer R, Brindley C, Orfanos CE, Plewig G, Wokalek H, et al. Acitretin versus etretinate in psoriasis: clinical and pharmacokinetic results of a German multicenter study. J Am Acad Dermatol. 1988;19:458–468
  116. Kragballe K, Jansen CT, Geiger JM, Bjerke JR, Falk ES, Gip L, et al. A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis: results of a Nordic multicenter study. Acta Derm Venereol. 1989;69:35–40
  117. van de Kerkhof PC, Cambazard F, Hutchinson PE, Haneke E, Wong E, Souteyrand P, et al. The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis. Br J Dermatol. 1998;138:84–89
  118. Geiger JM. Efficacy of acitretin in severe psoriasis. Skin Therapy Lett. 2003;8:1–37
  119. Ozawa A, Ohkido M, Haruki Y, Kobayashi H, Ohkawara A, Ohno Y, et al. Treatments of generalized pustular psoriasis: a multicenter study in Japan. J Dermatol. 1999;26:141–149
  120. Wolska H, Jablonska S, Bounameaux Y. Etretinate in severe psoriasis: results of double-blind study and maintenance therapy in pustular psoriasis. J Am Acad Dermatol. 1983;9:883–889
  121. Buccheri L, Katchen BR, Karter AJ, Cohen SR. Acitretin therapy is effective for psoriasis associated with human immunodeficiency virus infection. Arch Dermatol. 1997;133:711–715
  122. David M, Hodak E, Lowe NJ. Adverse effects of retinoids. Med Toxicol Adverse Drug Exp. 1988;3:273–288
  123. Koo J, Nguyen Q, Gambla C. Advances in psoriasis therapy. Adv Dermatol. 1997;12:47–73
  124. Yamauchi PS, Rizk D, Kormilli T, Patnaik R, Lowe NJ. Systemic retinoids. In:  Weinstein GD,  Gottlieb AB editor. Therapy of moderate to severe psoriasis. New York: Marcel Dekker Inc; 2003;p. 137–150
  125. Food and Drug Administration (FDA). Acitretin, FDA package insert. Available from: URL:http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm?fuseaction=Search.DrugDetails. Accessed January 19, 2009.
  126. Vahlquist A. Long-term safety of retinoid therapy. J Am Acad Dermatol. 1992;27(Suppl):S29–S33
  127. Malloy MJ, Kane JP. A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Adv Intern Med. 2001;47:111–136
  128. Roenigk HH, Callen JP, Guzzo CA, Katz HI, Lowe N, Madison K, et al. Effects of acitretin on the liver. J Am Acad Dermatol. 1999;41:584–588
  129. van Ditzhuijsen TJ, van Haelst UJ, van Dooren-Greebe RJ, van de Kerkhof PC, Yap SH. Severe hepatotoxic reaction with progression to cirrhosis after use of a novel retinoid (acitretin). J Hepatol. 1990;11:185–188
  130. DiGiovanna JJ, Sollitto RB, Abangan DL, Steinberg SM, Reynolds JC. Osteoporosis is a toxic effect of long-term etretinate therapy. Arch Dermatol. 1995;131:1263–1267
  131. Vincent V, Zabraniecki L, Loustau O, Godfrin B, Latour FB, Railhac JJ, et al. Acitretin-induced enthesitis in a patient with psoriatic arthritis. Joint Bone Spine. 2005;72:326–329
  132. Okada N, Nomura M, Morimoto S, Ogihara T, Yoshikawa K. Bone mineral density of the lumbar spine in psoriatic patients with long term etretinate therapy. J Dermatol. 1994;21:308–311
  133. Van Dooren-Greebe RJ, Lemmens JA, De Boo T, Hangx NM, Kuijpers AL, Van de Kerkhof PC. Prolonged treatment with oral retinoids in adults: no influence on the frequency and severity of spinal abnormalities. Br J Dermatol. 1996;134:71–76
  134. Lebwohl M, Menter A, Koo J, Feldman SR. Combination therapy to treat moderate to severe psoriasis. J Am Acad Dermatol. 2004;50:416–430
  135. Lebwohl M, Drake L, Menter A, Koo J, Gottlieb AB, Zanolli M, et al. Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis. J Am Acad Dermatol. 2001;45:544–553
  136. Iest J, Boer J. Combined treatment of psoriasis with acitretin and UVB phototherapy compared with acitretin alone and UVB alone. Br J Dermatol. 1989;120:665–670
  137. Lebwohl M. Acitretin in combination with UVB or PUVA. J Am Acad Dermatol. 1999;41(Suppl):S22–S24
  138. Lowe NJ, Prystowsky JH, Bourget T, Edelstein J, Nychay S, Armstrong R. Acitretin plus UVB therapy for psoriasis: comparisons with placebo plus UVB and acitretin alone. J Am Acad Dermatol. 1991;24:591–594
  139. Ruzicka T, Sommerburg C, Braun-Falco O, Koster W, Lengen W, Lensing W, et al. Efficiency of acitretin in combination with UV-B in the treatment of severe psoriasis. Arch Dermatol. 1990;126:482–486
  140. Spuls PI, Rozenblit M, Lebwohl M. Retrospective study of the efficacy of narrowband UVB and acitretin. J Dermatolog Treat. 2003;14(Suppl):17–20
  141. Lauharanta J, Geiger JM. A double-blind comparison of acitretin and etretinate in combination with bath PUVA in the treatment of extensive psoriasis. Br J Dermatol. 1989;121:107–112
  142. Saurat JH, Geiger JM, Amblard P, Beani JC, Boulanger A, Claudy A, et al. Randomized double-blind multicenter study comparing acitretin-PUVA, etretinate-PUVA and placebo-PUVA in the treatment of severe psoriasis. Dermatologica. 1988;177:218–224
  143. Tanew A, Guggenbichler A, Honigsmann H, Geiger JM, Fritsch P. Photochemotherapy for severe psoriasis without or in combination with acitretin: a randomized, double-blind comparison study. J Am Acad Dermatol. 1991;25:682–684
  144. Bavinck JN, Tieben LM, Van der Woude FJ, Tegzess AM, Hermans J, ter Schegget J, et al. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol. 1995;13:1933–1938
  145. McKenna DB, Murphy GM. Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin. Br J Dermatol. 1999;140:656–660
  146. McNamara IR, Muir J, Galbraith AJ. Acitretin for prophylaxis of cutaneous malignancies after cardiac transplantation. J Heart Lung Transplant. 2002;21:1201–1205
  147. Yuan ZF, Davis A, Macdonald K, Bailey RR. Use of acitretin for the skin complications in renal transplant recipients. N Z Med J. 1995;108:255–256
  148. Nijsten TE, Stern RS. Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study. J Am Acad Dermatol. 2003;49:644–650
  149. Du Vivier A, Munro DD, Verbov J. Treatment of psoriasis with azathioprine. Br Med J. 1974;1:49–51
  150. Greaves MW, Dawber R. Azathioprine in psoriasis. Br Med J. 1970;2:237–238
  151. Anstey AV, Wakelin S, Reynolds NJ. Guidelines for prescribing azathioprine in dermatology. Br J Dermatol. 2004;151:1123–1132
  152. Altmeyer PJ, Matthes U, Pawlak F, Hoffmann K, Frosch PJ, Ruppert P, et al. Antipsoriatic effect of fumaric acid derivatives: results of a multicenter double-blind study in 100 patients. J Am Acad Dermatol. 1994;30:977–981
  153. Gollnick H, Altmeyer P, Kaufmann R, Ring J, Christophers E, Pavel S, et al. Topical calcipotriol plus oral fumaric acid is more effective and faster acting than oral fumaric acid monotherapy in the treatment of severe chronic plaque psoriasis vulgaris. Dermatology. 2002;205:46–53
  154. Mrowietz U, Christophers E, Altmeyer P. Treatment of psoriasis with fumaric acid esters: results of a prospective multicenter study; German multicenter study. Br J Dermatol. 1998;138:456–460
  155. Peeters AJ, Dijkmans BA, van der Schroeff JG. Fumaric acid therapy for psoriatic arthritis: a randomized, double-blind, placebo-controlled study. Br J Rheumatol. 1992;31:502–504
  156. Mrowietz U, Asadullah K. Dimethylfumarate for psoriasis: more than a dietary curiosity. Trends Mol Med. 2005;11:43–48
  157. Kolbach DN, Nieboer C. Fumaric acid therapy in psoriasis: results and side effects of 2 years of treatment. J Am Acad Dermatol. 1992;27:769–771
  158. Raschka C, Koch HJ. Longterm treatment of psoriasis using fumaric acid preparations can be associated with severe proximal tubular damage. Hum Exp Toxicol. 1999;18:738–739
  159. Layton AM, Sheehan-Dare RA, Goodfield MJ, Cotterill JA. Hydroxyurea in the management of therapy resistant psoriasis. Br J Dermatol. 1989;121:647–653
  160. Kumar B, Saraswat A, Kaur I. Rediscovering hydroxyurea: its role in recalcitrant psoriasis. Int J Dermatol. 2001;40:530–534
  161. Ranjan N, Sharma NL, Shanker V, Mahajan VK, Tegta GR. Methotrexate versus hydroxycarbamide (hydroxyurea) as a weekly dose to treat moderate-to-severe chronic plaque psoriasis: a comparative study. J Dermatolog Treat. 2007;18:295–300
  162. Smith CH. Use of hydroxyurea in psoriasis. Clin Exp Dermatol. 1999;24:2–6
  163. Kaltwasser JP, Nash P, Gladman D, Rosen CF, Behrens F, Jones P, et al. Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum. 2004;50:1939–1950
  164. Prakash A, Jarvis B. Leflunomide: a review of its use in active rheumatoid arthritis. Drugs. 1999;58:1137–1164
  165. Marinari R, Fleischmajer R, Schragger AH, Rosenthal AL. Mycophenolic acid in the treatment of psoriasis: long-term administration. Arch Dermatol. 1977;113:930–932
  166. Zhou Y, Rosenthal D, Dutz J, Ho V. Mycophenolate mofetil (CellCept) for psoriasis: a two-center, prospective, open-label clinical trial. J Cutan Med Surg. 2003;7:193–197
  167. Geilen CC, Arnold M, Orfanos CE. Mycophenolate mofetil as a systemic antipsoriatic agent: positive experience in 11 patients. Br J Dermatol. 2001;144:583–586
  168. Gupta AK, Ellis CN, Siegel MT, Duell EA, Griffiths CE, Hamilton TA, et al. Sulfasalazine improves psoriasis: a double-blind analysis. Arch Dermatol. 1990;126:487–493
  169. Watkinson G. Sulphasalazine: a review of 40 years' experience. Drugs. 1986;32(Suppl):1–11
  170. Lebwohl M, Freeman AK, Chapman MS, Feldman SR, Hartle JE, Henning A. Tacrolimus ointment is effective for facial and intertriginous psoriasis. J Am Acad Dermatol. 2004;51:723–730
  171. Yan J, Chen SL, Wang XL, Zhou W, Wang FS. Meta-analysis of tacrolimus ointment for atopic dermatitis in pediatric patients. Pediatr Dermatol. 2008;25:117–120
  172. Bos JD, Witkamp L, Zonnevald IM, Ruzicka T, Szarmach H, Szczerkowska-Dobosz A. 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;132:419–423
  173. Zackheim HS, Maibach HI. Treatment of psoriasis with 6-thioguanine. Australas J Dermatol. 1988;29:163–167
  174. Zackheim HS, Glogau RG, Fisher DA, Maibach HI. 6-Thioguanine treatment of psoriasis: experience in 81 patients. J Am Acad Dermatol. 1994;30:452–458
  175. Silvis NG, Levine N. Pulse dosing of thioguanine in recalcitrant psoriasis. Arch Dermatol. 1999;135:433–437
  176. Black RL, O'Brien WM, Vanscott EJ, Auerbach R, Eisen AZ, Bunim JJ. Methotrexate therapy in psoriatic arthritis; double-blind study on 21 patients. JAMA. 1964;189:743–747
  177. Willkens RF, Williams HJ, Ward JR, Egger MJ, Reading JC, Clements PJ, et al. Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Arthritis Rheum. 1984;27:376–381
  178. Mahrle G, Schulze HJ, Brautigam M, Mischer P, Schopf R, Jung EG, et al. Anti-inflammatory efficacy of low-dose cyclosporin A in psoriatic arthritis: a prospective multicenter study. Br J Dermatol. 1996;135:752–757
  179. Salvarani C, Macchioni P, Olivieri I, Marchesoni A, Cutolo M, Ferraccioli G, et al. A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis. J Rheumatol. 2001;28:2274–2282
  180. Berbis P, Bun H, Geiger JM, Rognin C, Durand A, Serradimigni A, et al. Acitretin (RO10-1670) and oral contraceptives: interaction study. Arch Dermatol Res. 1988;280:388–389
  181. Snow JL, Gibson LE. The role of genetic variation in thiopurine methyltransferase activity and the efficacy and/or side effects of azathioprine therapy in dermatologic patients. Arch Dermatol. 1995;131:193–197
  182. Lee JC, Gladman DD, Schentag CT, Cook RJ. The long-term use of azathioprine in patients with psoriatic arthritis. J Clin Rheumatol. 2001;7:160–165
  183. Grundmann-Kollmann M, Mooser G, Schraeder P, Zollner T, Kaskel P, Ochsendorf F, et al. Treatment of chronic plaque-stage psoriasis and psoriatic arthritis with mycophenolate mofetil. J Am Acad Dermatol. 2000;42:835–837
  184. Dougados M, vam der Linden S, Leirisalo-Repo M, Huitfeldt B, Juhlin R, Veys E, et al. Sulfasalazine in the treatment of spondylarthropathy: a randomized, multicenter, double-blind, placebo-controlled study. Arthritis Rheum. 1995;38:618–627
  185. Ruzicka T. Psoriatic arthritis: new types, new treatments. Arch Dermatol. 1996;132:215–219

 Funding sources: None.

 The authors' conflict of interest/disclosure statements appear at the end of the article.

PII: S0190-9622(09)00390-9

doi: 10.1016/j.jaad.2009.03.027

Journal of the American Academy of Dermatology
Volume 61, Issue 3 , Pages 451-485 , September 2009

Article Tools