American Journal of Clinical Dermatology

, Volume 1, Issue 1, pp 27–39 | Cite as

Risk-Benefit Assessment of Methotrexate in the Treatment of Severe Psoriasis

  • Astrid L.A. Kuijpers
  • Peter C.M. van de Kerkhof
Review Article


Methotrexate is an established and highly effective systemic treatment for severe psoriasis, including the pustular and erythrodermic forms. It has been widely used during the last 3 decades. For this reason, the long term adverse effects of methotrexate are well known, in contrast to other relatively new systemic treatments like cyclosporin and retinoids. The most frequent adverse effects occurring during methotrexate therapy are abnormal liver function tests, nausea and gastric complaints.

The most feared adverse effects are myelosuppression and hepatotoxicity. Because hepatotoxicity is related to a high cumulative dose of methotrexate, rotational therapy or an intermittent instead of a continuous treatment schedule are advised. The histological assessment of liver biopsies, according to the international guidelines, remains the gold standard for detection of liver damage until equally reliable noninvasive screening methods for liver damage — tentatively dynamic hepatic scintigraphy (DHS) or measurement of levels of serum amino-terminal propeptide of type III procollagen — are well evaluated.

Low dose methotrexate therapy is relatively well tolerated, provided that there is careful patient selection and regular monitoring for adverse effects and drug interactions during methotrexate therapy is carried out. The long term clinical efficacy and relative safety of methotrexate remain impressive.


Methotrexate Psoriasis Etretinate Severe Psoriasis Methotrexate Therapy 
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  1. 1.
    van de Kerkhof P.C.M. Methotrexate. In: Mier P.D., van de Kerkhof P.C.M., editors. Textbook of psoriasis. Edinburgh: Churchill Livingstone, 1986; 233–251Google Scholar
  2. 2.
    Roenigk Jr H.H., Maibach H.I. Methotrexate. In: Roenigk H.H., Maibach H.I., editors. Psoriasis. 2nd ed. New York: Marcel Dekker, 1991; 563–575Google Scholar
  3. 3.
    Weinstein G.D. Commentary: three decades of folic acid antagonists in dermatology. Arch Dermatol 1983; 119: 525–527PubMedCrossRefGoogle Scholar
  4. 4.
    Gubner R. Effect of aminopterin on epithelial tissues. Arch Dermatol Syphilol 1951; 64: 688–699CrossRefGoogle Scholar
  5. 5.
    Edmundson W.F., Guy W.B. Treatment of psoriasis with folic acid antagonists. Arch Dermatol 1958; 78: 200–203CrossRefGoogle Scholar
  6. 6.
    Weinstein G.D., Frost P. Methotrexate for psoriasis. A new therapeutic schedule. Arch Dermatol 1971; 103: 33–38PubMedCrossRefGoogle Scholar
  7. 7.
    Ashton R.E., Millward Sadler G.H., White J.E. Complications in methotrexate treatment of psoriasis with particular reference to liver fibrosis. J Invest Dermatol 1982; 79: 229–232PubMedCrossRefGoogle Scholar
  8. 8.
    van de Kerkhof P.C., Hoefnagels W.H., van Haelst U.J., et al. Methotrexate maintenance therapy and liver damage in psoriasis. Clin Exp Dermatol 1985; 10: 194–200PubMedCrossRefGoogle Scholar
  9. 9.
    Zachariae H., Kragballe K., Sogaard H. Methotrexate induced liver cirrhosis. Studies including serial liver biopsies during continued treatment. Br J Dermatol 1980; 102: 407–412PubMedCrossRefGoogle Scholar
  10. 10.
    Nyfors A. Liver biopsies from psoriatics related to methotrexate therapy. Findings in post-methotrexate liver biopsies from 160 psoriatics. Acta Pathol Microbiol Scand A 1977; 85: 511–518PubMedGoogle Scholar
  11. 11.
    Jackson R.C. Biological effects of folic acid antagonists with antineoplastic activity. Pharmacol Ther 1984; 25: 61–82PubMedCrossRefGoogle Scholar
  12. 12.
    Burkhart C.G. Treatment of psoriasis with methotrexate and folinic acid [letter]. J Am Acad Dermatol 1980; 3: 207–208PubMedCrossRefGoogle Scholar
  13. 13.
    Ive F.A., De Saram C.F. Methotrexate and the citrovorum factor in the treatment of psoriasis. Trans St Johns Hosp Dermatol Soc 1970; 56: 45–47PubMedGoogle Scholar
  14. 14.
    Kremer J.M. Methotrexate update. Scand J Rheumatol 1996; 25: 341–344PubMedCrossRefGoogle Scholar
  15. 15.
    Rothenberg R.J., Graziano F.M., Grandone J.T., et al. The use of methotrexate in steroidresistant systemic lupus erythematosus. Arthritis Rheum 1988; 31: 612–615PubMedCrossRefGoogle Scholar
  16. 16.
    van den Hoogen F.H., Boerbooms A.M., Swaak A.J., et al. Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 1996; 35: 364–372PubMedCrossRefGoogle Scholar
  17. 17.
    Kozarek R.A., Patterson D.J., Gelfand M.D., et al. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease [see comments]. Ann Intern Med 1989; 110: 353–356PubMedGoogle Scholar
  18. 18.
    Mullarkey M.F. Methotrexate and asthma [see comments]. J Allergy Clin Immunol 1991; 88: 272–274PubMedCrossRefGoogle Scholar
  19. 19.
    Schwartz P.M., Barnett S.K., Atillasoy E.S., et al. Methotrexate induces differentiation of human keratinocytes. Proc Natl Acad Sci U S A 1992; 89: 594–598PubMedCrossRefGoogle Scholar
  20. 20.
    Lammers A.M. van de Kerkhof P.C., Mier P.D. Reduction of leukotriene B4-induced intraepidermal accumulation of polymorphonuclear leukocytes by methotrexate in psoriasis. Br J Dermatol 1987; 116: 667–671PubMedCrossRefGoogle Scholar
  21. 21.
    Ternowitz T., Bjerring P., Andersen P.H., et al. Methotrexate inhibits the human C5ainduced skin response in patients with psoriasis. J Invest Dermatol 1987; 89: 192–196PubMedCrossRefGoogle Scholar
  22. 22.
    Cronstein B.N. Molecular therapeutics. Methotrexate and its mechanism of action. Arthritis Rheum 1996; 39: 1951–1960PubMedCrossRefGoogle Scholar
  23. 23.
    Jeffes E.W., McCullough J.L., Pittelkow M.R., 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: 183–188PubMedCrossRefGoogle Scholar
  24. 24.
    Weinstein G.D., Jeffes E., McCullough J.L. Cytotoxic and immunologic effects of methotrexate in psoriasis. J Invest Dermatol 1990; 95: 49S–52SCrossRefGoogle Scholar
  25. 25.
    Chang D.M., Baptiste P., Schur P.H. The effect of antirheumatic drugs on interleukin 1 (IL-1) activity and IL-1 and IL-1 inhibitor production by human monocytes. J Rheumatol 1990; 17: 1148–1157PubMedGoogle Scholar
  26. 26.
    Segal R., Mozes E., Yaron M., et al. The effects of methotrexate on the production and activity of interleukin-1. Arthritis Rheum 1989; 32: 370–377PubMedCrossRefGoogle Scholar
  27. 27.
    McCullough J.L., Snyder D., Weinstein G.D. Factors affecting human percutaneous penetration of methotrexate and its analogues in vitro. J Invest Dermatol 1976; 67: 26–30PubMedCrossRefGoogle Scholar
  28. 28.
    Bjerring P., Beck H.I., Zachariae H., et al. Topical treatment of psoriatic skin with methotrexate cream: a clinical, pharmacokinetic, and histological study. Acta Derm Venereol 1986; 66: 515–519PubMedGoogle Scholar
  29. 29.
    Said S., Jeffes E.W.B, Weinstein G.D. Systemic treatment; methotrexate. Clin Dermatol 1997; 15: 781–797PubMedCrossRefGoogle Scholar
  30. 30.
    Kamel R.S., al Hakiem M.H., Rademaker M., et al. Pharmacokinetics of small doses of methotrexate in patients with psoriasis. Acta Derm Venereol 1988; 68: 267–270PubMedGoogle Scholar
  31. 31.
    Wan S.H., Huffman D.H., Azarnoff D.L., et al. Pharmacokinetics of 1-beta-Darabinofuranosylcytosine in humans. Cancer Res 1974; 34: 392–397PubMedGoogle Scholar
  32. 32.
    Jones S.K., Aherne G.W., Campbell M.J., et al. Methotrexate pharmacokinetics in psoriatic patients developing hepatic fibrosis. Arch Dermatol 1986; 122: 666–669PubMedCrossRefGoogle Scholar
  33. 33.
    Hendel L., Hendel J., Johnsen A., et al. Intestinal function and methotrexate absorption in psoriatic patients. Clin Exp Dermatol 1982; 7: 491–497PubMedCrossRefGoogle Scholar
  34. 34.
    Pinkerton C.R., Welshman S.G., Glasgow J.F., et al. Can food influence the absorption of methotrexate in children with acute lymphoblastic leukaemia? Lancet 1980; 2: 944–946PubMedCrossRefGoogle Scholar
  35. 35.
    Bleyer W.A. The clinical pharmacology of methotrexate: new applications of an old drug. Cancer 1978; 41: 36–51PubMedCrossRefGoogle Scholar
  36. 36.
    Tung J.P., Maibach H.I. The practical use of methotrexate in psoriasis. Drugs 1990; 40: 697–712PubMedCrossRefGoogle Scholar
  37. 37.
    Taylor J.R., Halprin K.M. Effect of sodium salicylate and indomethacin on methotrexate-serum albumin binding. Arch Dermatol 1977; 113: 588–591PubMedCrossRefGoogle Scholar
  38. 38.
    Hendel J. Clinical pharmacokinetics of methotrexate in psoriasis therapy. Dan Med Bull 1985; 32: 329–337PubMedGoogle Scholar
  39. 39.
    Hendel J., Nyfors A. Nonlinear renal elimination kinetics of methotrexate due to saturation of renal tubular reabsorption. Eur J Clin Pharmacol 1984; 26: 121–124PubMedCrossRefGoogle Scholar
  40. 40.
    Lawrence J.R., Steele W.H., Stuart J.F., et al. Dose dependent methotrexate elimination following bolus intravenous injection. Eur J Clin Pharmacol 1980; 17: 371–374PubMedCrossRefGoogle Scholar
  41. 41.
    Nierenberg D.W., Mamelok R.D. Toxic reaction to methotrexate in a patient receiving penicillin and furosemide: a possible interaction [letter]. Arch Dermatol 1983; 119: 449–450PubMedCrossRefGoogle Scholar
  42. 42.
    Singh R.R., Malaviya A.N., Pandey J.N., et al. Fatal interaction between methotrexate and naproxen [letter]. Lancet 1986; 1: 1390PubMedCrossRefGoogle Scholar
  43. 43.
    Maiche A.G. Acute renal failure due to concomitant action of methotrexate and indomethacin [letter]. Lancet 1986; 1: 1390PubMedCrossRefGoogle Scholar
  44. 44.
    Thomas D.R., Dover J.S., Camp R.D. Pancytopenia induced by the interaction between methotrexate and trimethoprim-sulfamethoxazole [letter]. J Am Acad Dermatol 1987; 17: 1055–1056PubMedCrossRefGoogle Scholar
  45. 45.
    Thomas M.H., Gutterman L.A. Methotrexate toxicity in a patient receiving trimethoprimsulfamethoxazole. J Rheumatol 1986; 13: 440–441PubMedGoogle Scholar
  46. 46.
    Groenendal H., Rampen F.H. Methotrexate and trimethoprim-sulphamethoxazole—a potentially hazardous combination [see comments]. Clin Exp Dermatol 1990; 15: 358–360PubMedCrossRefGoogle Scholar
  47. 47.
    Larsen F.G., Nielsen Kudsk F., Jakobsen P., et al. Interaction of etretinate with methotrexate pharmacokinetics in psoriatic patients. J Clin Pharmacol 1990; 30: 802–807PubMedGoogle Scholar
  48. 48.
    Evans W.E., Christensen M.L. Drug interactions with methotrexate. J Rheumatol 1985; 12: 15–20Google Scholar
  49. 49.
    Steele W.H., Stuart J.F., Lawrence J.R., et al. Enhancement of methotrexate absorption by subdivision of dose. Cancer Chemother Pharmacol 1979; 3: 235–237PubMedCrossRefGoogle Scholar
  50. 50.
    Roenigk Jr H.H., Auerbach R., Maibach H.I., et al. Methotrexate in psoriasis: revised guidelines. J Am Acad Dermatol 1988; 19: 145–156PubMedCrossRefGoogle Scholar
  51. 51.
    Collins P., Rogers S. The efficacy of methotrexate in psoriasis—a review of 40 cases. Clin Exp Dermatol 1992; 17: 257–260PubMedCrossRefGoogle Scholar
  52. 52.
    Kumar B., Dhar S., Handa S., Kaur I. Methotrexate in childhood psoriasis. Pediatr Dermatol 1994; 11: 271–273PubMedCrossRefGoogle Scholar
  53. 53.
    van Dooren Greebe R.J., Kuijpers A.L.A., Mulder J., et al. Methotrexate revisited: effects of long-term treatment in psoriasis. Br J Dermatol 1994; 130: 204–210CrossRefGoogle Scholar
  54. 54.
    Baker H. Methotrexate the conservative treatment for psoriasis. In: Farber E.M., Cox A.J., editors. Psoriasis: Proceedings of the second international symposium. New York: Yorke Medical Books, 1976; 235–242Google Scholar
  55. 55.
    Ellis C.N., Fradin M.S., Hamilton T.A. Duration of remission during maintenance cyclosporin therapy for psoriasis: relationship to maintenance dose and degree of improvement during initial therapy. Arch Dermatol 1995; 131: 791–795PubMedCrossRefGoogle Scholar
  56. 56.
    Fradin M.S., Ellis C.N., Voorhees J.J. Efficacy of cyclospporin a in psoriasis: a summary of the United States’ experience. Br J Dermatol 1990; 122: 21–25PubMedCrossRefGoogle Scholar
  57. 57.
    Nyfors A. Benefits and adverse drug experiences during long-term methotrexate treatment of 248 psoriatics. Dan Med Bull 1978; 25: 208–211PubMedGoogle Scholar
  58. 58.
    Zachariae H., Zachariae E. Methotrexate treatment of psoriatic arthritis. Acta Derm Venereol 1987; 67: 270–273PubMedGoogle Scholar
  59. 59.
    Black R., O’Brien W., Van Scott E., et al. Methotrexate therapy in psoriatic arthritis. JAMA 1964; 189: 743–747PubMedCrossRefGoogle Scholar
  60. 60.
    Weinblatt M.E., Coblyn J.S., Fox D.A., et al. Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 1985; 312: 818–822PubMedCrossRefGoogle Scholar
  61. 61.
    Gollnick H. Acitretin in psoriasis: an update. In: Saurat J., editor. Retinoids 10 years on. Basel: Karger, 1991; 204–213Google Scholar
  62. 62.
    Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993; 28: 466–469PubMedCrossRefGoogle Scholar
  63. 63.
    Zonneveld I.M., Bakker W.K., Dijkstra P.F., et al. Methotrexate osteopathy in longterm, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis. Arch Dermatol 1996; 132: 184–187PubMedCrossRefGoogle Scholar
  64. 64.
    Kettunen R., Huikuri H.V., Oikarinen A., et al. Methotrexate-linked ventricular arrhythmias. Acta Derm Venereol 1995; 75: 391–392PubMedGoogle Scholar
  65. 65.
    Duhra P., Foulds I.S. Methotrexate-induced impairment of taste acuity. Clin Exp Dermatol 1988; 13: 126–127PubMedCrossRefGoogle Scholar
  66. 66.
    Pearce H.P., Wilson B.B. Erosion of psoriatic plaques: an early sign of methotrexate toxicity. J Am Acad Dermatol 1996; 35: 835–838PubMedCrossRefGoogle Scholar
  67. 67.
    Hausknecht R.U. Methotrexate and misoprostol to terminate early pregnancy. N Engl J Med 1995; 333: 537–540PubMedCrossRefGoogle Scholar
  68. 68.
    Roenigk Jr H.H., Auerbach R., Maibach H., et al. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol 1998; 38: 478–485PubMedCrossRefGoogle Scholar
  69. 69.
    Morris L.F., Harrod M.J., Menter M.A., et al. Methotrexate and reproduction in men: case report and recommendations. J Am Acad Dermatol 1993; 29: 913–916PubMedCrossRefGoogle Scholar
  70. 70.
    Zachariae H. Methotrexate side-effects [see comments]. Br J Dermatol 1990; 122 Suppl. 36Google Scholar
  71. 71.
    Hendel J., Nyfors A. Impact of methotrexate therapy on the folate status of psoriatic patients. Clin Exp Dermatol 1985; 10: 30–35PubMedCrossRefGoogle Scholar
  72. 72.
    Weinblatt M.E., Fraser P. Elevated mean corpuscular volume as a predictor of hematologic toxicity due to methotrexate therapy. Arthritis Rheum 1989; 32: 1592–1596PubMedCrossRefGoogle Scholar
  73. 73.
    Morgan S.L., Baggott J.E., Vaughn W.H., et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebocontrolled trial [see comments]. Ann Intern Med 1994; 121: 833–841PubMedGoogle Scholar
  74. 74.
    Stern R.S., Zierler S., Parrish J.A. Methotrexate used for psoriasis and the risk of noncutaneous or cutaneous malignancy. Cancer 1982; 50: 869–872PubMedCrossRefGoogle Scholar
  75. 75.
    Nyfors A., Jensen H. Frequency of malignant neoplasms in 248 long-term methotrexate-treated psoriatics. A preliminary study. Dermatologica 1983; 167: 260–261PubMedCrossRefGoogle Scholar
  76. 76.
    Benedict W.F., Baker M.S., Haroun L., et al. Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test. Cancer Res 1977; 37: 2209–2213PubMedGoogle Scholar
  77. 77.
    Boffa M.J., Chalmers R.J., Haboubi N.Y., et al. Sequential liver biopsies during longterm methotrexate treatment for psoriasis: a reappraisal. Br J Dermatol 1995; 133: 774–778PubMedCrossRefGoogle Scholar
  78. 78.
    Kamen B.A., Nylen P.A., Camitta B.M., et al. Methotrexate accumulation and folate depletion in cells as a possible mechanism of chronic toxicity to the drug. Br J Haematol 1981; 49: 355–360PubMedCrossRefGoogle Scholar
  79. 79.
    Barak A.J., Tuma D.J., Beckenhauer H.C. Methotrexate hepatotoxicity. J Am Coll Nutr 1984; 3: 93–96PubMedGoogle Scholar
  80. 80.
    Nyfors A., Poulsen H. Liver biopsies from psoriatics related to methotrexate therapy. 2. Findings before and after methotexate therapy in 88 patients. A blind study. Acta Pathol Microbiol Scand A 1976; 84: 262–270PubMedGoogle Scholar
  81. 81.
    Roenigk Jr H.H., Auerbach R., Bergfeld W.F. A cooperative prospective study of the effects of chemotherapy of psoriasis on liver biopsies. In: Farber E.M., Cox A.J., editors. Psoriasis: Proceedings of the second international symposium. New York: Yorke Medical Books, 1976; 243–248Google Scholar
  82. 82.
    Mitchell D., Smith A., Rowan B., et al. Serum type III procollagen peptide, dynamic liver function tests and hepatic fibrosis in psoriatic patients receiving methotrexate. Br J Dermatol 1990; 122: 1–7PubMedCrossRefGoogle Scholar
  83. 83.
    Zachariae H., Grunnet E., Sogaard H. Liver biopsy in methotrexate-treated psoriatics-a re-evalution. Acta Derm Venereol 1975; 55: 291–296PubMedGoogle Scholar
  84. 84.
    Robinson J.K., Baughman R.D., Auerbach R., et al. Methotrexate hepatotoxicity in psoriasis. Consideration of liver biopsies at regular intervals. Arch Dermatol 1980; 116: 413–415PubMedCrossRefGoogle Scholar
  85. 85.
    Paul B.S., Momtaz K., Stern R.S., et al. Combined methotrexate—ultraviolet B therapy in the treatment of psoriasis. J Am Acad Dermatol 1982; 7: 758–762PubMedCrossRefGoogle Scholar
  86. 86.
    Newman M., Auerbach R., Feiner H., et al. The role of liver biopsies in psoriatic patients receiving long-term methotrexate treatment. Improvement in liver abnormalities after cessation of treatment. Arch Dermatol 1989; 125: 1218–1224PubMedCrossRefGoogle Scholar
  87. 87.
    Reese L.T., Grisham J.W., Aach R.D., et al. Effects of methotrexate on the liver in psoriasis. J Invest Dermatol 1974; 62: 597–602PubMedCrossRefGoogle Scholar
  88. 88.
    Zachariae H., Sogaard H. Methotrexate-induced liver cirrhosis. A follow-up. Dermatologica 1987; 175: 178–182PubMedCrossRefGoogle Scholar
  89. 89.
    Zachariae H., Sogaard H., Heickendorff L. Methotrexate-induced liver cirrhosis. Clinical, histological and serological studies—a further 10-year follow-up. Dermatology 1996; 192: 343–346PubMedCrossRefGoogle Scholar
  90. 90.
    Gilbert S.C., Klintmalm G., Menter A., et al. Methotrexate-induced cirrhosis requiring liver transplantation in three patients with psoriasis. A word of caution in light of the expanding use of this ‘steroid-sparing’ agent [see comments]. Arch Intern Med 1990; 150: 889–891PubMedCrossRefGoogle Scholar
  91. 91.
    Creswell S.N., Burrows D. Liver biopsies in psoriatics—complications and evaluation. Int J Dermatol 1980; 19: 217–219PubMedCrossRefGoogle Scholar
  92. 92.
    Sherlock S., Dick R., Van Leeuwen D.J. Liver biopsy today. The Royal Free Hospital experience. J Hepatol 1985; 1: 75–85PubMedCrossRefGoogle Scholar
  93. 93.
    McGill D.B., Rakela J., Zinsmeister A.R., et al. A 21-year experience with major hemorrhage after percutaneous liver biopsy [see comments]. Gastroenterology 1990; 99: 1396–1400PubMedGoogle Scholar
  94. 94.
    Rademaker M., Webb J.A., Lowe D.G., et al. Magnetic resonance imaging as a screening procedure for methotrexate induced liver damage. Br J Dermatol 1987; 117: 311–316PubMedCrossRefGoogle Scholar
  95. 95.
    Saverymuttu S.H., Joseph A.E., Maxwell J.D. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J Clin Res Ed 1986; 292: 13–15PubMedCrossRefGoogle Scholar
  96. 96.
    Verschuur A.C., van Everdingen J.J., Cohen E.B., et al. Liver biopsy versus ultrasound in methotrexate-treated psoriasis: a decision analysis. Int J Dermatol 1992; 31: 404–409PubMedCrossRefGoogle Scholar
  97. 97.
    Mitchell D., Johnson R.J., Testa H.J., et al. Ultrasound and radionuclide scans—poor indicators of liver damage in patients treated with methotrexate. Clin Exp Dermatol 1987; 12: 243–245PubMedCrossRefGoogle Scholar
  98. 98.
    Paramsothy J., Strange R., Sharif H., et al. The use of antipyrine clearance to measure liver damage in psoriatic patients receiving methotrexate. Br J Dermatol 1988; 119: 761–765PubMedCrossRefGoogle Scholar
  99. 99.
    Hendel J., Poulsen H., Nyfors B., et al. Changes in liver histology during methotrexate therapy of psoriasis correlated to the concentration of methotrexate and folate in erythrocytes. Acta Pharmacol Toxicol Copenh 1985; 56: 321–326PubMedCrossRefGoogle Scholar
  100. 100.
    McHenry P.M., Bingham E.A., Callender M.E., et al. Dynamic hepatic scintigraphy in the screening of psoriatic patients for methotrexate-induced hepatotoxicity. Br J Dermatol 1992; 127: 122–125PubMedCrossRefGoogle Scholar
  101. 101.
    Ferguson W.R., Laird J.D., Cranly K. Early dynamic studies as an adjunct to liver scintigraphy in the investigation of diffuse liver disease. J Nucl Med 1981; 22: 88Google Scholar
  102. 102.
    van Dooren Greebe R.J., Kuijpers A.L.A., Buijs W.C., et al. The value of dynamic hepatic scintigraphy and serum aminoterminal propeptide of type III procollagen for early detection of methotrexate-induced hepatic damage in psoriasis patients. Br J Dermatol 1996; 134: 481–487CrossRefGoogle Scholar
  103. 103.
    Zachariae H., Sogaard H., Heickendorff L. Serum aminoterminal propeptide of type III procollagen. A non-invasive test for liver fibrogenesis in methotrexate-treated psoriatics. Acta Derm Venereol 1989; 69: 241–244PubMedGoogle Scholar
  104. 104.
    Zachariae H., Aslam H.M., Bjerring P., et al. Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis [see comments]. J Am Acad Dermatol 1991; 25: 50–53PubMedCrossRefGoogle Scholar
  105. 105.
    Risteli J., Sogaard H., Oikarinen A., et al. Aminoterminal propeptide of type III procollagen in methotrexate-induced liver fibrosis and cirrhosis. Br J Dermatol 1988; 119: 321–325PubMedCrossRefGoogle Scholar
  106. 106.
    Prockop D.J., Kivirikko K.I., Tuderman L., et al. The biosynthesis of collagen and its disorders (1st of 2 pts). N Engl J Med 1979; 1301: 13–23CrossRefGoogle Scholar
  107. 107.
    Risteli J., Niemi S., Trivedi P., et al. Rapid equilibrium radioimmunoassay for the amino-terminal propeptide of human type III procollagen. Clin Chem 1988; 34: 715–718PubMedGoogle Scholar
  108. 108.
    Frei A., Zimmermann A., Weigand K. The N-terminal propeptide of collagen type III in serum reflects activity and degree of fibrosis in patients with chronic liver disease. Hepatology 1984; 4: 830–834PubMedCrossRefGoogle Scholar
  109. 109.
    Horslev Petersen K., Saxne T., Haar D., et al. The aminoterminal-type-III procollagen peptide and proteoglycans in serum and synovial fluid of patients with rheumatoid arthritis or reactive arthritis. Rheumatol Int 1988; 8: 1–9CrossRefGoogle Scholar
  110. 110.
    Zachariae H., Halkier Sorensen L., Heickendorff L. Serum aminoterminal propeptide of type III procollagen in progressive systemic sclerosis and localized scleroderma. Acta Derm Venereol 1989; 69: 66–70PubMedGoogle Scholar
  111. 111.
    McLaren M.I., Fleming J.S., Walmsley B.H., et al. Dynamic liver scanning in cirrhosis. Br J Surg 1985; 72: 394–396PubMedCrossRefGoogle Scholar
  112. 112.
    Kanzler M.H., Gorsulowsky D. Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis [letter; comment]. J Am Acad Dermatol 1992; 26: 509PubMedCrossRefGoogle Scholar
  113. 113.
    Boffa M.J., Smith A., Chalmers R.J., et al. Serum type III procollagen aminopeptide for assessing liver damage in methotrexate-treated psoriatic patients. Br J Dermatol 1996; 135: 538–544PubMedCrossRefGoogle Scholar
  114. 114.
    Oogarah P.K., Rowland P.I., Mitchell D.M., et al. Abnormalities of serum type III procollagen aminoterminal peptide in methotrexate-treated psoriatic patients with normal liver histology do not correlate with hepatic ultrastructural changes. Br J Dermatol 1995; 133: 512–518PubMedCrossRefGoogle Scholar
  115. 115.
    Boffa M.J., Chalmers R.J. Methotrexate for psoriasis. Clin Exp Dermatol 1996; 21: 399–408PubMedCrossRefGoogle Scholar
  116. 116.
    Themido R., Loureiro M., Pecegueiro M., et al. Methotrexate hepatotoxicity in psoriatic patients submitted to long-term therapy. Acta Derm Venereol 1992; 72: 361–364PubMedGoogle Scholar
  117. 117.
    Greaves M.W., Weinstein G.D. Treatment of psoriasis [see comments]. N Engl J Med 1995; 332: 581–588PubMedCrossRefGoogle Scholar
  118. 118.
    Adams J.D. Concurrent methotrexate and etretinate therapy for psoriasis [letter]. Arch Dermatol 1983; 119: 793PubMedCrossRefGoogle Scholar
  119. 119.
    Beck H.I., Foged E.K. Toxic hepatitis due to combination therapy with methotrexate and etretinate in psoriasis. Dermatologica 1983; 167: 94–96PubMedCrossRefGoogle Scholar
  120. 120.
    Jeffes E.W., III, Weinstein G.D. Methotrexate and other chemotherapeutic agents used to treat psoriasis. Dermatol Clin 1995; 13: 875–890PubMedGoogle Scholar
  121. 121.
    Weinstein G.D., White G.M. An approach to the treatment of moderate to severe psoriasis with rotational therapy. J Am Acad Dermatol 1993; 28: 454–459PubMedCrossRefGoogle Scholar
  122. 122.
    van Dooren Greebe R.J., Kuijpers A.L.A., Termorshuizen F, et al. Interruption of long-term methotrexate treatment in psoriasis. Evaluation of clinical course and laboratory parameters after discontinuation and reintroduction of weekly oral methotrexate. Acta Derm Venereol 1995; 75: 393–396Google Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Astrid L.A. Kuijpers
    • 1
  • Peter C.M. van de Kerkhof
    • 1
  1. 1.Department of DermatologyUniversity Hospital NijmegenNijmegenThe Netherlands

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