, Volume 40, Issue 5, pp 697–712

The Practical Use of Methotrexate in Psoriasis

  • Joseph P. Tung
  • Howard I. Maibach
Practical Therapeutic


Psoriasis is an inflammatory disease of the skin associated with increased epidermal proliferation. The aetiology of the disease is unknown, but there seems to be a genetic predisposition.

The goal of therapy in the treatment of psoriasis is to decrease the rate of epidermal proliferation and the underlying inflammation. Topical application of steroids and coal tar are the therapies of choice; however, for those patients with severe recalcitrant psoriasis who have failed conventional topical therapy methotrexate is an established alternative.

The use of methotrexate in psoriasis is limited by its toxicity, and proper patient selection and close monitoring are essential in achieving good clinical response. The dosage used should be the lowest that will maintain the patient in comfort, not necessarily that which produces total resolution. Caution should be exercised when other agents are used concurrently with methotrexate, and possible drug interactions should be identified as these may influence the effectiveness and toxicity of methotrexate therapy.

The common side effects associated with the use of methotrexate in psoriasis include bone marrow suppression, gastrointestinal symptoms and hepatotoxicity. Liver damage is a major concern in long term methotrexate therapy and thus liver biopsies are warranted to monitor any pathological changes. The drug is a known teratogen and should be avoided in pregnant patients. Women of childbearing age should use reliable contraception during therapy.

Patients should be made aware of the signs and symptoms of methotrexate toxicity and inform their physicians promptly as most adverse effects can be ameliorated with appropriate dosage adjustment. Methotrexate will continue to play a major role in the treatment of psoriasis and it is thus important that it be used safely.


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  1. Ackland SP, Schilsky RL. High-dose methotrexate: a critical reappraisal. Journal of Clinical Oncology 5: 2017–2031, 1987PubMedGoogle Scholar
  2. Anderson LL, Collins GJ, Ojima Y, Sullivan RD. A study of the distribution of methotrexate in human tissues and tumors. Cancer Research 30: 1344–1348, 1970PubMedGoogle Scholar
  3. Ashton RE, Millward-Sadler GH, White JE. Complications in methotrexate treatment of psoriasis with particular reference to liver fibrosis. Journal of Investigative Dermatology 79: 229–232, 1982PubMedCrossRefGoogle Scholar
  4. Balinska M, Galivan J, Coward JK. Efflux of methotrexate and its polyglutamate derivatives from hepatic cells in vitro. Cancer Research 42: 2751–2756, 1981Google Scholar
  5. Bertino JR. ‘Rescue’ techniques in cancer chemotherapy: use of leucovorin and other rescue agents after methotrexate treatment. Seminars in Oncology 4: 203–216, 1977PubMedGoogle Scholar
  6. Bjerring P, Beck HI, Zachariae H, Sogaard H. Topical treatment of psoriatic skin with methotrexate cream: a clinical, pharmacokinetic, and histological study. Acta Dermato-Venereologica (Stockholm) 66: 515–519, 1986Google Scholar
  7. Bleyer WA. The clinical pharmacology of methotrexate: new application of an old drug. Cancer 41: 36–51, 1978PubMedCrossRefGoogle Scholar
  8. Bleyer WA. New vistas for leucovorin in cancer chemotherapy. Cancer 63: 995–1007, 1989PubMedCrossRefGoogle Scholar
  9. Bos JD. The pathomechanisms of psoriasis; the skin immune system and cyclosporin. British Journal of Dermatology 118: 141–155, 1988PubMedCrossRefGoogle Scholar
  10. Carmichael AJ, Ryatt KS. Pneumocystis carinii pneumonia following methotrexate. Correspondence. British Journal of Dermatology 122: 291, 1990CrossRefGoogle Scholar
  11. Carson CW, Cannon GW, Egger MJ, Ward JR, Clegg DO. Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate. Seminars in Arthritis and Rheumatism 16: 186–195, 1987PubMedCrossRefGoogle Scholar
  12. Coe RO, Bull FE. Cirrhosis associated with methotrexate treatment of psoriasis. Journal of the American Medical Association 206: 1515–1520, 1968PubMedCrossRefGoogle Scholar
  13. Coulson IH, McKenzie J, Neild VS, Joseph AE, Marsden RA. A comparison of liver ultrasound with liver biopsy histology in psoriatics receiving long-term methotrexate therapy. British Journal of Dermatology 116: 491–495, 1987PubMedCrossRefGoogle Scholar
  14. Duhra P, Foulds IS. Methotrexate-induced impairment of taste acuity. Clinical and Experimental Dermatology 13: 126–127, 1988PubMedCrossRefGoogle Scholar
  15. Edelman J, Russell AS, Biggs DF, Rothwell RS, Coates J. Methotrexate levels, a guide to therapy. Clinical and Experimental Rheumatology 1: 153–156, 1983PubMedGoogle Scholar
  16. Evans WE, Christensen ML. Drug interactions with methotrexate. Journal of Rheumatology (Suppl. 12): 15–20, 1985Google Scholar
  17. Geronemus RG, Auerbach R, Tobias H. Liver biopsies v liver scans in methotrexate-treated patients with psoriasis. Archives of Dermatology 118: 649–651, 1982PubMedCrossRefGoogle Scholar
  18. Gottlieb AB. Immunologic mechanisms in psoriasis. Journal of the American Academy of Dermatology 18: 1376–1380, 1988PubMedCrossRefGoogle Scholar
  19. Gubner R. Effect of aminopterin on epithelial tissues. Archives of Dermatology and Syphilology 64: 688–699, 1951PubMedCrossRefGoogle Scholar
  20. Halprin KM, Fukui K, Ohkawara A. Blood levels of methotrexate and the treatment of psoriasis. Archives of Dermatology 103: 243–249, 1971PubMedCrossRefGoogle Scholar
  21. Hanno R, Gruber GG, Owen LG, Callen JP. Methotrexate in psoriasis. Journal of the American Academy of Dermatology 2: 171–174, 1980PubMedGoogle Scholar
  22. Harrison PV. Methotrexate-induced epidermal necrosis. British Journal of Dermatology 116: 867–869, 1987PubMedCrossRefGoogle Scholar
  23. Hatcher RA, Guest F, Stewart F, Stewart GK, Trussell J, et al. Contraceptive technology, 14th ed., pp. 150–162, Irvington Publishers Inc., New York, 1988–1989Google Scholar
  24. Hendel J. Clinical pharmacokinetics of methotrexate in psoriasis therapy. Danish Medical Bulletin 32: 329–337, 1985PubMedGoogle Scholar
  25. Hendel J, Nyfors A. Nonlinear renal elimination kinetics of methotrexate due to saturation of renal tubular reabsorption. European Journal of Clinical Pharmacology 26: 121–124, 1984PubMedCrossRefGoogle Scholar
  26. Hendel L, Hendel J, Johnsen A, Gudmand-Hoyer E. Intestinal function and methotrexate absorption in psoriatic patients. Clinical and Experimental Dermatology 7: 491–498, 1982PubMedCrossRefGoogle Scholar
  27. Hoffmeister RT. Methotrexate therapy in rheumatoid arthritis: 15 years experience. American Journal of Medicine 75: 69–73, 1983PubMedCrossRefGoogle Scholar
  28. Jolivet J, Chabner BA. Intracellular pharmacokinetics of methotrexate polyglutamates in human breast cancer cells. Journal of Clinical Investigation 72: 773–778, 1983PubMedCrossRefGoogle Scholar
  29. Jolivet J, Cowans KH, Curt GA, Clendeninn NJ, Chabner BA. The pharmacology and clinical use of methotrexate. New England Journal of Medicine 309: 1094–1104, 1983PubMedCrossRefGoogle Scholar
  30. Jones SK, Aherne GW, Campbell MJ, White JE. Methotrexate pharmacokinetics in psoriatic patients developing hepatic fibrosis. Archives of Dermatology 122: 666–669, 1986PubMedCrossRefGoogle Scholar
  31. Kremer JM, Lee JK. The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis and Rheumatism 29: 822–831, 1986PubMedCrossRefGoogle Scholar
  32. Kremer JM, Lee JK. Long-term prospective study of the use of methotrexate in rheumatoid arthritis. Arthritis and Rheumatism 31: 577–584, 1988PubMedCrossRefGoogle Scholar
  33. Kristensen LO, Weismann K, H utters L. Renal function and the rate of disappearance of methotrexate from serum. European Journal of Clinical Pharmacology 8: 439–444, 1975PubMedCrossRefGoogle Scholar
  34. Lambert RE, Kaye BR. Methotrexate and the acquired immunodeficiency syndrome. Correspondence. Annals of Internal Medicine 106: 773, 1987Google Scholar
  35. Lanse SB, Arnold GL, Gowans JDC, Kaplan MM. Low incidence of hepatotoxicity associated with long term, low dose oral methotrexate in the treatment of refractory psoriasis, psoriatic arthritis, and rheumatoid arthritis: an acceptable risk/benefit ratio. Digestive Diseases and Sciences 30: 104–109, 1985PubMedCrossRefGoogle Scholar
  36. Lawrence JR, Steele WH, Stuart JFB, McNeill CA, McVie JG, et al. Dose dependent methotrexate elimination following bolus intravenous injection. European Journal of Clinical Pharmacology 17: 371–374, 1980PubMedCrossRefGoogle Scholar
  37. Lewis JH, Schiff E. Methotrexate induced chronic liver injury: guidelines for detection and prevention. American Journal of Gastroenterology 88: 1337–1345, 1988Google Scholar
  38. Mackenzie AH. Hepatotoxicity of prolonged methotrexate therapy for rheumatoid arthritis. Cleveland Clinic Quarterly 52: 129–135, 1985PubMedGoogle Scholar
  39. Menard DB, Gisselbrecht C, Maarty M, Reyes F, Dhumeaux D. Antineoplastic agents and the liver. Gastroenterology 78: 142–164, 1980PubMedGoogle Scholar
  40. Michaelsson G. Increased chemotactic activity of neutrophil leukocytes in psoriasis. British Journal of Dermatology 103: 351–356, 1980PubMedCrossRefGoogle Scholar
  41. Miller JA, Dodd H, Rustin MHA, Lees WR, Levene GM, et al. Ultrasound as a screening procedure for methotrexate-induced hepatic damage in severe psoriasis. British Journal of Dermatology 113: 699–705, 1985PubMedCrossRefGoogle Scholar
  42. Morison WL, Khosrow Momtaz T, Parrish JA, Fitzpatrick TB. Combined methotrexate-PUVA therapy in the treatment of psoriasis. Journal of the American Academy of Dermatology 6: 46–51, 1982PubMedCrossRefGoogle Scholar
  43. Ng HWF, MacFarlane AW, Graham RM, Verbov JL. Near fatal drug interactions with methotrexate given for psoriasis. Correspondence. British Medical Journal 295: 752–753, 1987CrossRefGoogle Scholar
  44. Nirenberg A, Mosende C, Mehta BM, Gisolfi A, Rosen G. High-dose methotrexate with citrovorum factor rescue: predictive value of serum methotrexate concentrations and corrective measures to avert toxicity. Cancer Treatment Reports 61: 779–783, 1977PubMedGoogle Scholar
  45. Nyfors A. Liver biopsies from psoriatics related to methotrexate therapy. Acta Pathologica et Microbiologica Scandinavica (Section A) 85: 511–518, 1977Google Scholar
  46. Nyfors A. Benefits and adverse drug experiences during long-term methotrexate treatment of 248 psoriatics. Danish Medical Bulletin 25: 208–211, 1978PubMedGoogle Scholar
  47. Nyfors A, Poulsen H. Liver biopsies from psoriatics related to methotrexate therapy. Acta Pathologica et Microbiologica Scandinavica (Section A) 84: 262–270, 1976Google Scholar
  48. Paul BS, Khosrow Momtaz T, Stern RS, Arndt KA, Parrish JA. Combined methotrexate-ultraviolet B therapy in the treatment of psoriasis. Journal of the American Academy of Dermatology 7: 758–762, 1982PubMedCrossRefGoogle Scholar
  49. Perry WH. Methotrexate and teratogenesis. Correspondence. Archives of Dermatology 119: 874, 1983CrossRefGoogle Scholar
  50. Phillips TJ, Jones DH, Baker H. Pulmonary complications following methotrexate therapy. Journal of the American Academy of Dermatology 16: 373–375, 1987PubMedCrossRefGoogle Scholar
  51. Phillips TJ, Wallis PJ, Jones DH, Baker H. Pulmonary function in patients on long-term low-dose methotrexate. British Journal of Dermatology 115: 657–662, 1986PubMedCrossRefGoogle Scholar
  52. Pinkerton GR, Glasgow JFT, Welshman SG, Bridges JM. Can food influence the absorption of methotrexate in children with acute lymphoblastic leukemia. Lancet 2: 944–945, 1980PubMedCrossRefGoogle Scholar
  53. Pitman SW, Frei III E. Weekly methotrexate — calcium leucovorin rescue: effect of alkalinization on nephrotoxicity; pharmacokinetics in the CNS; and in the CNS non-Hodgkin’s lymphoma. Cancer Treatment Reports 61: 695–701, 1977PubMedGoogle Scholar
  54. Rall D, Mead JAR, Freireich EJ, Scott EV, Hertz R, et al. Folic acid antagonists: effects on the cell and the patient. Combined clinical staff conference at the National Institute of Health. Annals of Internal Medicine 59: 931–956, 1963Google Scholar
  55. Rees RB, Bennett JH, Bostick WL. Aminopterin for psoriasis. Archives of Dermatology 72: 133–143, 1955PubMedCrossRefGoogle Scholar
  56. Reese LT, Grisham JW, Aach RD, Eisen AZ. Effects of methotrexate on the liver in psoriasis. Journal of Investigative Dermatology 62: 597–602, 1974PubMedCrossRefGoogle Scholar
  57. Reynolds FS, Lee WM. Hepatotoxicity after long term methotrexate therapy. Southern Medical Journal 79: 536–539, 1986PubMedCrossRefGoogle Scholar
  58. Robinson JK, Baughman RD. Auerbach R, Cimis RJ. Methotrexate hepatotoxicity in psoriasis. Archives of Dermatology 116: 413–415, 1980Google Scholar
  59. Roenigk Jr HH, Auerbach R, Bergfeld WF, et al. A cooperative prospective study of the effects of chemotherapy of psoriasis on liver biopsies. In Farber EM & Cox AJ (Eds) Psoriasis: Proceedings of the Second International Symposium, pp. 243–248, Yorke Medical Books, New York, 1977Google Scholar
  60. Roenigk HH, Auerbach R, Maibach HI, Weinstein GD. Methotrexate in psoriasis: revised guidelines. Journal of the American Academy of Dermatology 19: 145–156, 1988PubMedCrossRefGoogle Scholar
  61. Roenigk HH, Fowler-Bergfeld W, Curtis GH. Methotrexate for psoriasis in weekly oral doses. Archives of Dermatology 99: 86–93, 1969PubMedCrossRefGoogle Scholar
  62. Shamberger RC, Rosenberg SA, Seipp CA, Sherins RJ. Effects of high-dose methotrexate and vincristine on ovarian and testicular functions in patients undergoing postoperative adjuvant treatment of osteosarcoma. Cancer Treatment Reports 65: 739–746, 1981PubMedGoogle Scholar
  63. Shupack JL, Webster GF. Pancytopenia following low-dose oral methotrexate therapy for psoriasis. Journal of the American Medical Association 259: 3594–3596, 1988PubMedCrossRefGoogle Scholar
  64. Shuster S. Dermatogenic enteropathy. Lancet 1: 1367–1368, 1965CrossRefGoogle Scholar
  65. St Clair EW, Rice JR, Snyderman R. Pneumonitis complicating low-dose methotrexate therapy in rheumatoid arthritis. Archives of Internal Medicine 145: 2035–2038, 1985PubMedCrossRefGoogle Scholar
  66. Stern RS, Zierler S, Parrish JA. Methotrexate used for psoriasis and the risk of noncutaneous or cutaneous malignancy. Cancer 50: 869–872, 1982PubMedCrossRefGoogle Scholar
  67. Stewart WD, Wallace SM, Runikis JD. Absorption and local action of methotrexate in human and mouse skin. Archives of Dermatology 106: 357–361, 1972PubMedCrossRefGoogle Scholar
  68. Stockley IH. Methotrexate-NSAID interactions. Correspondence. Drug Intelligence and Clinical Pharmacy 21: 546, 1987Google Scholar
  69. Sussman A, Leonard JM. Psoriasis, methotrexate, and oligospermia. Archives of Dermatology 116: 215–217, 1980PubMedCrossRefGoogle Scholar
  70. Ternowitz T, Herlin T. Neutrophil and monocyte chemotaxis in methotrexate-treated psoriasis patients. Acta Dermato-Venereologica (Stockholm) (Suppl. 120): 23–26, 1985Google Scholar
  71. Thomas DR, Dover JS, Camp RDR. Pancytopenia induced by the interaction between methotrexate and trimethoprim-sul-famethoxazole. Correspondence. Journal of the American Academy of Dermatology 17: 1055–1056, 1987CrossRefGoogle Scholar
  72. Tuyp E, MacKie RM. Combination therapy for psoriasis with methotrexate and etretinate. Journal of the American Academy of Dermatology 14: 70–73, 1986PubMedCrossRefGoogle Scholar
  73. Van de Kerkhof PCM, Hoefnagels WHL, Van Haelst UJGM, Mali JWH. Methotrexate maintenance therapy and liver damage in psoriasis. Clinical and Experimental Dermatology 10: 194–200, 1985PubMedCrossRefGoogle Scholar
  74. Van Scott EJ, Ekel TM. Kinetics of hyperplasia in psoriasis. Archives of Dermatology 88: 373–381, 1963CrossRefGoogle Scholar
  75. Voorhees JJ, Janzen MK, Harrell ER, Chakrabarti SG. Cytogenetic evaluation of methotrexate treated psoriatic patients. Archives of Dermatology 100: 269–274, 1969PubMedCrossRefGoogle Scholar
  76. Wahba A, Cohen HA, Bar-Eli M, Gallily R. Enhanced chemotactic and phagocytic activities of leukocytes in psoriasis vulgaris. Journal of Investigative Dermatology 71: 186–188, 1978PubMedCrossRefGoogle Scholar
  77. Waiden PAM, Bagshawe KD. Reproductive performance of women successfully treated for gestational trophoblastic tumors. American Journal of Obstetrics and Gynecology 125: 1108–1114, 1976Google Scholar
  78. Warkany J. Aminopterin and methotrexate: folic acid deficiency. Teratology 17: 353–358, 1978PubMedCrossRefGoogle Scholar
  79. Weinblatt ME, Coblyn JS, Fox DA, Fraser PA, Holdsworth DE, et al. Efficacy of low-dose methotrexate in rheumatoid arthritis. New England Journal of Medicine 312: 818–822, 1985PubMedCrossRefGoogle Scholar
  80. Weinblatt ME, Trentham DE, Fraser PA, Holdsworth DE, Falchuk KR, et al. Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis and Rheumatism 31: 167–175, 1988PubMedCrossRefGoogle Scholar
  81. Weinstein A, Marlowe S, Korn J, Farouhar F. Low dose methotrexate treatment of rheumatoid arthritis: long term observations. American Journal of Medicine 79: 331–337, 1985PubMedCrossRefGoogle Scholar
  82. Weinstein GD. Methotrexate: diagnosis and treatment drugs five years later. Annals of Internal Medicine 86: 199–204, 1977PubMedGoogle Scholar
  83. Weinstein GD. Chemotherapy for psoriasis. Dermatologic Clinics 2: 431–438, 1984Google Scholar
  84. Weinstein GD, Goldfaden G, Frost P. Methotrexate: mechanism of action on DNA synthesis in psoriasis. Archives of Dermatology 104: 236–243, 1971PubMedCrossRefGoogle Scholar
  85. Weinstein GD, McCullough JL. Cell proliferation kinetics. In Roenigk H & Maibach H (Eds) Psoriasis, Vol. 5, pp. 233–247, Mercel Dekker Inc., 1985Google Scholar
  86. Weinstein GD, McCullough JL, Olsen E. Topical methotrexate therapy for psoriasis. Archives of Dermatology 125: 227–230, 1989PubMedCrossRefGoogle Scholar
  87. Weinstein GD, Roenigk H, Maibach HI, Cosmides J, Halprin K, et al. Psoriasis-liver-methotrexate interactions. Archives of Dermatology 108: 36–42, 1973CrossRefGoogle Scholar
  88. Wernick R, Smith DL. Central nervous system toxicity associated with weekly low-dose methotrexate treatment. Arthritis and Rheumatism 32: 770–775, 1989PubMedCrossRefGoogle Scholar
  89. Westwick TJ, Sheretz EF, McCarley D, Flowers FR. Delayed reactivation of sunburn by methotrexate: sparing of chronically sun-exposed skin. Cutis 39: 49–51, 1987PubMedGoogle Scholar
  90. Wright N. Cell population kinetics in human epidermis. International Journal of Dermatology 16: 449–463, 1977PubMedCrossRefGoogle Scholar
  91. Zachariae H, Grunnet E, Sogaard H. Liver biopsy in methotrexate treated psoriatics: a reevaluation. Acta Dermato-Venereologica (Stockholm) 55: 291–296, 1975Google Scholar
  92. Zachariae H, Kragballe K, Sogaard H. Methotrexate induced liver cirrhosis. British Journal of Dermatology 102: 407–412, 1980PubMedCrossRefGoogle Scholar
  93. Zachariae H, Schroder H, Foged E, Sogaard H. Methotrexate hepatotoxicity and concentrations of methotrexate and folate in erythrocytes: relation to liver fibrosis and cirrhosis. Acta Dermato-Venereologica (Stockholm) 67: 336–340, 1987Google Scholar
  94. Zimmerman CL, Franz TJ, Slattery JT. Persistence of antifolate activity in skin of rats following systemic administration of methotrexate. Journal of Investigative Dermatology 82: 57–61, 1983CrossRefGoogle Scholar
  95. Zimmerman CL, Franz TJ, Slattery JT. Pharmacokinetics of the poly-glutamyl metabolites of methotrexate in skin and other tissues of rats and hairless mice. Journal of Pharmacology and Experimental Therapeutics 231: 242–247, 1984PubMedGoogle Scholar

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© Adis International Limited 1990

Authors and Affiliations

  • Joseph P. Tung
    • 1
  • Howard I. Maibach
    • 1
  1. 1.Departments of Pharmaceutical Services and DermatologyUniversity of CaliforniaSan FranciscoUSA

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