Corticosteroids in Rheumatoid Arthritis
Summary
Glucocorticosteroids are widely used in the treatment of patients with rheumatoid arthritis. Initially there was much enthusiasm for their use, arising from the striking relief of symptoms seen in patients with rheumatoid arthritis treated with corticosteroids. When the wide array of potentially serious adverse effects became apparent, the use of corticosteroids decreased. More recently, however, the careful use of corticosteroids in patients with rheumatoid arthritis has been generally accepted. New insights into the mechanisms of action of corticosteroids, especially their effects on the immune system and the hypothalamic-pituitary-adrenal axis, have provided more insight into, and rationale for, the use of corticosteroids in rheumatoid arthritis.
Clinical data on the effectiveness of low dosage oral corticosteroids, high dosage systemic corticosteroids and intra-articular injections of corticosteroids are scarce. In contrast, data on the adverse effects of oral low dosage corticosteroids are abundant. In the last few years, strategies have been developed to at least partially prevent 2 of the main adverse effects: peptic ulcer disease and osteoporosis. Some practical guidelines on the use of corticosteroids in the management of rheumatoid arthritis conclude this review.
Keywords
Rheumatoid Arthritis Corticosteroid Adis International Limited Rheumatol Peptic Ulcer DiseasePreview
Unable to display preview. Download preview PDF.
References
- 1.Hench PS, Kendall EC, Slocumb CH, et al. Effects of cortisone acetate and pituitary ACTH on rheumatoid arthritis, rheumatic fever and certain other conditions: a study in clinical physiology. Arch Intern Med 1950; 85: 546–666CrossRefGoogle Scholar
- 2.Weiss MM. Corticosteroids in rheumatoid arthritis. Semin Arthritis Rheum 1989; 19: 9–21PubMedCrossRefGoogle Scholar
- 3.Kimberly RP. Glucocorticoids. Curr Opin Rheumatol 1994; 6: 273–80PubMedCrossRefGoogle Scholar
- 4.Boumpas DT, Chrousos GP, Wilder RL, et al. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993; 119: 1198–208PubMedGoogle Scholar
- 5.Hollenberg SM, Weinberger C, Ong ES, et al. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 1985; 318: 635–41PubMedCrossRefGoogle Scholar
- 6.Boumpas DT, Paliogianni F, Anastassiou ED, et al. Glucocorticosteroid action on the immune system: molecular and cellular aspects. Clin Exp Rheumatol 1991; 9: 413–23PubMedGoogle Scholar
- 7.Luisi BF, Xu WX, Otwinowski Z, et al. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 1991; 352: 497–505PubMedCrossRefGoogle Scholar
- 8.Drouin J, Sun YL, Tremblay S, et al. Homodimer formation is rate-limiting for high affinity DNA binding by glucocorticoid receptor. Mol Endocrinol 1992; 6: 1299–309PubMedCrossRefGoogle Scholar
- 9.Diamond MI, Miner JN, Yoshinaga SK, et al. Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science 1990; 249: 1266–72PubMedCrossRefGoogle Scholar
- 10.Akerblom TW, Slater ER, Beato M, et al. Negative regulation by glucocorticoid through interference with a cAMP responsive enhancer. Science 1988; 241: 530–3CrossRefGoogle Scholar
- 11.Fauci AS, Dale DC, Balow JE. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 1976; 84: 304–15PubMedGoogle Scholar
- 12.Pitzalis C, Panayi GS. Inhibition of leucocyte-endothelial interaction, homotypic and heterotypic adhesion by corticosteroids: a possible mechanism for their anti-inflammatory action. Arthritis Rheum 1993; 36: S246Google Scholar
- 13.Rook GAW, Hernandez-Pando R, Lightman SL. Hormones, peripherally activated prohormones and the regulation of the TH1/TH2 balance. Immunol Today 1994; 15: 301–3PubMedCrossRefGoogle Scholar
- 14.Paliogianni F, Ahuja SS, Balow JE, et al. Novel mechanism for inhibition of T cells by glucocorticoids: GC modulate signal transduction through IL-2 receptor. J Immunol 1993; 151: 4081–9PubMedGoogle Scholar
- 15.Butler WT, Rossen RD. Effects of corticosteroids on immunity in man: decreased serum IgG concentration caused by 3 to 5 days of high doses of methylprednisolon. J Clin Invest 1973; 52: 2629–40PubMedCrossRefGoogle Scholar
- 16.Sternberg EM, Wilder RL. Corticosteroids. In: McCarty DJ, Koopman WJ, editors. Arthritis and allied conditions. Philadelphia: Lea and Febiger, 1993: 665–82Google Scholar
- 17.O’Banion MK, Winn VD, Young DA. cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc Natl Acad Sci USA 1992; 89: 4888–92PubMedCrossRefGoogle Scholar
- 18.DeWitt DL, Meade EA, Smith WL. PGH synthase isoenzyme selectivity: the potential for safer nonsteroidal anti-inflammatory drugs. Am J Med 1993; 95(2A): 40–4CrossRefGoogle Scholar
- 19.Sternberg EM, Chrousos GP, Wilder RL, et al. The stress response and the regulation of inflammatory disease. Ann Intern Med 1992; 117: 854–66PubMedGoogle Scholar
- 20.Sutton RE, Koos GF, Le Moal M, et al. Corticotrophin releasing factor produces behavioral activation in rats. Nature 1982; 29: 331–3CrossRefGoogle Scholar
- 21.Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 1984; 5: 25–44PubMedCrossRefGoogle Scholar
- 22.West HF. Corticosteroid metabolism and rheumatoid arthritis. Ann Rheum Dis 1957; 16: 173–81PubMedCrossRefGoogle Scholar
- 23.Neeck G, Federlin K, Graef V, et al. Adrenal secretion of cortisol in patients with rheumatoid arthritis. J Rheumatol 1990; 17: 24–9PubMedGoogle Scholar
- 24.Vanden Brink HR, Blankenstein MA, Koppeschaar HPF, et al. Influence of disease activity on steroid hormone levels in peripheral blood of patients with rheumatoid arthritis. Clin Exp Rheumatol 1993; 11: 649–52PubMedGoogle Scholar
- 25.Vanden Brink HR, Van Wijk MJG, Bijlsma JWJ. Influence of steroid hormones on proliferation of peripheral blood mononuclear cells in patients with rheumatoid arthritis. Br J Rheumatol 1992; 31: 663–7PubMedCrossRefGoogle Scholar
- 26.Blowers CE, Jayson MI, Jasani MK. Dexamethasone modulated protein synthesis in polymorphonuclear leukocytes: response in rheumatoid arthritis. J Rheumatol 1988; 15: 785–90PubMedGoogle Scholar
- 27.Schlaghecke R, Kornely E, Wollenhaupt J, et al. Glucocorticoid receptors in rheumatoid arthritis. Arthritis Rheum 1992; 35: 740–4PubMedCrossRefGoogle Scholar
- 28.Chikanza IC, Petrou P, Kingsley G, et al. Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis. Arthritis Rheum 1992; 35: 1281–8PubMedGoogle Scholar
- 29.Sheehan HL, Summers VK. The syndrome of hypopituitarism. Q J Med 1949; 18: 319–78PubMedGoogle Scholar
- 30.George E, Kirwan JR. Corticosteroid therapy in rheumatoid arthritis. Baillieres Clin Rheumatol 1990; 4: 621–47PubMedCrossRefGoogle Scholar
- 31.Medical Research Council and Nuffield Foundation. A comparison of cortisone and aspirin in the treatment of early cases of rheumatoid arthritis. BMJ 1954; 29: 1223–7Google Scholar
- 32.Medical Research Council and Nuffield Foundation. A comparison of prednisolone with aspirin or other analgesics in the treatment of RA. Ann Rheum Dis 1959; 18; 173–87CrossRefGoogle Scholar
- 33.West HF. Rheumatoid arthritis. The relevance of clinical knowledge to research activities. Abstr World Med 1967; 41: 401–17Google Scholar
- 34.Empire Rheumatism Council. Multicentre controlled trial comparing cortisone acetate and acetylsalicylic acid in the long term treatment of rheumatoid arthritis. Ann Rheum Dis 1957; 16: 277–89CrossRefGoogle Scholar
- 35.Harris ED, Emkey RD, Nicholas JE, et al. Low dose prednisolone therapy in RA: a double blind study. J Rheumatol 1983; 10: 713–21PubMedGoogle Scholar
- 36.Ritchie DM, Boyle JA, McInnes JM, et al. Clinical studies with an articular index for the assessment of joint tenderness in patients with RA. Q J Med 1968; 37: 393–406PubMedGoogle Scholar
- 37.Buchanan WW, Stephen LJ, Buchanan HM. Are ‘homeopathic’ doses of oral corticosteroids effective in RA?. Clin Exp Rheumatol 1988; 6: 281–4PubMedGoogle Scholar
- 38.Docken WP. Low-dose prednisone therapy. Rheum Dis Clin North Am 1989; 15: 569–76PubMedGoogle Scholar
- 39.Caldwell JR, Furst DE. The efficacy and safety of low-dose corticosteroids for rheumatoid arthritis. Semin Arthritis Rheum 1991; 21: 1–11PubMedCrossRefGoogle Scholar
- 40.Byron MA, Mowat AG. Corticosteroid prescribing in RA: the fiction and the fact. Br J Rheumatol 1985; 24: 164–8PubMedCrossRefGoogle Scholar
- 41.Kimberly RP. Pulse methyl prednisolone in SLE. Clin Rheum Dis 1982; 8: 261–78PubMedGoogle Scholar
- 42.Liebling MR, Leib E, McLaughin K, et al. Pulse methylprednisolone in rheumatoid arthritis: a double-blind cross-over trial. Ann Intern Med 1981; 94: 21–6PubMedGoogle Scholar
- 43.Kimberly RP. Glucocorticoid therapy for rheumatic diseases. Curr Opin Rheumatol 1992; 4: 325–31PubMedCrossRefGoogle Scholar
- 44.Vanden Brink HR, Van Wijk MJG, Geurtsen RGM, et al. Influence of corticosteroid pulse therapy on the serum levels of soluble interleukin 2 receptor, interleukin 6 and interleukin 8 in patients with rheumatoid arthritis. J Rheumatol 1994; 21: 430–4PubMedGoogle Scholar
- 45.Williams IA, Baylis EM, Shipley ME. A double-blind placebocontrolled trial of methylprednisolone pulse therapy in active rheumatoid disease. Lancet 1982; 1: 237–40CrossRefGoogle Scholar
- 46.Pentikaïnen PT. Pharmacological aspects of corticosteroid pulse therapy. Scand J Rheumatol 1984; 54S: 6–9CrossRefGoogle Scholar
- 47.Neumann V, Hopkins R, Dixon J, et al. Combination therapy with pulsed methylprednisolone in rheumatoid arthritis. Ann Rheum Dis 1985; 44: 747–51PubMedCrossRefGoogle Scholar
- 48.Bijlsma JWJ, Schenk Y, Ramselaar AC, et al. Methylprednisolone pulse therapy in conjunction with azathioprine in rheumatoid arthritis. Clin Rheumatol 1986; 5: 499–504PubMedGoogle Scholar
- 49.Hansen TM, Dickmeiss E, Jans H, et al. Combination of methylprednisolone pulse therapy and remission inducing drugs in rheumatoid arthritis. Ann Rheum Dis 1987; 46: 290–5PubMedCrossRefGoogle Scholar
- 50.Hansen TM, Krijger P, Elling H, et al. Double blind placebo controlled trial of pulse treatment with methylprednisolone combined with disease modifying drugs in rheumatoid arthritis. BMJ 1990; 301: 268–70PubMedCrossRefGoogle Scholar
- 51.Vander Veen MJ, Bijlsma JWJ. The effect of methylprednisolone pulse therapy in methotrexate treatment of rheumatoid arthritis. Clin Rheumatol 1993; 12: 500–5PubMedCrossRefGoogle Scholar
- 52.Choy EHS, Kingsley GH, Corkill MM, et al. Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the induction phase of chrysotherapy. Br J Rheumatol 1993; 32: 734–9PubMedCrossRefGoogle Scholar
- 53.Schumacher HR, editor. Primer on the rheumatic diseases. Atlanta: Arthritis Foundation, 1993: 302–4Google Scholar
- 54.Weusten BCAM, Jacobs JWG, Bijlsma JWJ. Corticosteroid pulse therapy in active rheumatoid arthritis. Semin Arthritis Rheum 1993; 23: 183–92PubMedCrossRefGoogle Scholar
- 55.Bijlsma JWJ, Duursma SA, Huber-Bruning O. Bone metabolism during methylprednisolone pulse therapy in rheumatoid arthritis. Ann Rheum Dis 1986; 45: 757–60PubMedCrossRefGoogle Scholar
- 56.Bijlsma JWJ, Duursma SA, Bosch R, et al. Acute changes in calcium and bone metabolism during methylprednisolone pulse therapy in rheumatoid arthritis. Br J Rheumatol 1988; 27: 215–9PubMedCrossRefGoogle Scholar
- 57.Lems WF, Jacobs JWG, Van den Brink HR, et al. Transient decrease in osteocalcin and markers of type I collagen turnover during high-dose corticosteroid pulse therapy in rheumatoid arthritis. Br J Rheumatol 1993; 32: 787–9PubMedCrossRefGoogle Scholar
- 58.Gray RG, Tenenbaum J, Gottlieb NL. Local corticosteroid injection treatment in rheumatic disorders. Semin Arthritis Rheum 1981; 10: 231–54PubMedCrossRefGoogle Scholar
- 59.Hollander J. Intra-synovial corticosteroid therapy in arthritis. Md Med J 1969; 19: 62–6Google Scholar
- 60.Chatham W, William G, Moreland L, et al. Intraarticular corticosteroid injections: should we rest the joints? Arthritis Care Res 1989; 2: 70–4PubMedCrossRefGoogle Scholar
- 61.Cooper C, Kirwan JR. The risk of local and systemic corticosteroid administration. Baillière’s Clin Rheumatol 1990; 4: 305–32CrossRefGoogle Scholar
- 62.Alarcon-Segovia D, Ward LE. Marked destructive changes occurring in osteo-arthritic finger joints after intra-articular injection of corticosteroids. Arthritis Rheum 1966; 9: 443–9PubMedCrossRefGoogle Scholar
- 63.McCarthy DJ, Hogan JM. Inflammatory reaction after intrasynovial injection of microcrystalline adrenocorticosteroids esters. Arthritis Rheum 1964; 7: 359–67CrossRefGoogle Scholar
- 64.Markin HJ, Conger KA. The acute effects of intra-articular hydrocortisone on articular cartilage in rabbits. J Bone Joint Surg 1966; 48A: 1383–8Google Scholar
- 65.Malfait AM, Verbruggen G, Almquist KF, et al. Corticosteroids protect proteoglycan synthesis in the co-culture of mono-nuclear cells and human articular chondrocytes. Arthritis Rheum 1993; 36: 9C 24Google Scholar
- 66.Saag KG, Koehnke R, Caldwell JR, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 1994; 96: 115–23PubMedCrossRefGoogle Scholar
- 67.Piper JM, Ray WA, Daugherty JR, et al. Corticosteroid use and peptic ulcer disease: role of non-steroidal anti-inflammatory drugs. Ann Intern Med 1991; 114: 735–40PubMedGoogle Scholar
- 68.Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991; 115: 787–96PubMedGoogle Scholar
- 69.Schlaghecke R, Konzaly E, Santen RT, et al. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. N Engl J Med 1992; 326: 226–30PubMedCrossRefGoogle Scholar
- 70.La Rochelle GE, La Rochelle AG, Ratner RE, et al. Recovery of the hypothalamic pituitary-adrenal axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med 1993; 95: 258–64CrossRefGoogle Scholar
- 71.Kass EM, Finland M. Corticosteroids and infectious diseases. Adv Intern Med 1958; 9: 45–80PubMedGoogle Scholar
- 72.Streck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis 1989; 11: 954–63CrossRefGoogle Scholar
- 73.Kalbak K. Incidence of arteriosclerosis in patients with rheumatoid arthritis receiving long-term corticosteroid therapy. Ann Rheum Dis 1972; 31: 196–200PubMedCrossRefGoogle Scholar
- 74.Nashel DJ. Is atherosclerosis a complication of long-term corticosteroid treatment? Am J Med 1986; 80: 925–9PubMedCrossRefGoogle Scholar
- 75.Ettinger WH, Hazzard WR. Prednisone increases very low density lipoprotein and high density lipoprotein in healthy men. Metabolism 1988; 37: 1055–8PubMedCrossRefGoogle Scholar
- 76.Gough AKS, Lilley J, Eyre S, et al. Generalised bone loss in patients with early rheumatoid arthritis. Lancet 1994; 344: 23–7PubMedCrossRefGoogle Scholar
- 77.Sambrook PN, Eisman JA, Champion GD, et al. Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis. Arthritis Rheum 1988; 31: 973–8PubMedCrossRefGoogle Scholar
- 78.Chavossieux P, Pastoureau P, Chapuy MC, et al. Glucocorticoid induced inhibition of osteoblastic bone formation in ewes: a biochemical and histomorphometric study. Osteoporos Int 1993; 3: 97–102CrossRefGoogle Scholar
- 79.Lems WF, Jacobs JWG, Van Rijn HJM, et al. Oral calcium supplementation prevents the changes in osteocalcin during low dose prednisone therapy. Calcif Tissue Int 1993; 52 Suppl. 78: 312Google Scholar
- 80.Meunier PJ, Dempster DW, Edouard C, et al. Bone histomorphometry in corticosteroid-induced osteoporosis in Cushing’s Syndrome. Adv Exp Med Biol 1984; 171: 191–200PubMedGoogle Scholar
- 81.Hahn TJ, Hulstead LR, Baran DT. Effects of short term glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab 1981; 52: 111–5PubMedCrossRefGoogle Scholar
- 82.Suzuki Y, Ichikawa Y, Saito E, et al. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism 1983; 32: 151–6PubMedCrossRefGoogle Scholar
- 83.Spector TD, Sambrook PN. Steroid osteoporosis. BMJ 1993; 307: 519–20PubMedCrossRefGoogle Scholar
- 84.Spector TD, Hale GM, McCluskey EV, et al. Risk of vertebral fracture in women with RA. BMJ 1993; 306: 558PubMedCrossRefGoogle Scholar
- 85.Lukert BP, Raisz LG. Glucocorticoid induced osteoporosis: pathogenesis and management. Ann Int Med 1990; 112: 352–64PubMedGoogle Scholar
- 86.Pocock NA, Eisman JA, Dumstan CR, et al. Recovery from steroid induced osteoporosis. Ann Intern Med 1987; 107: 319–23PubMedGoogle Scholar
- 87.Sambrook PN, Eisman JA, Champion GD, et al. Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids. Ann Rheum Dis 1986; 45: 950–3PubMedCrossRefGoogle Scholar
- 88.Laan RFJM, Van Riel PLCM, Van Erming LJT, et al. Vertebral osteoporosis in rheumatoid arthritis patients: effect of low dose prednisone therapy. Br J Rheumatol 1992; 31: 91–6PubMedCrossRefGoogle Scholar
- 89.Dykman TR, Gluck OS, Murphy WA, et al. Evaluation of factors associated with glucocorticoid induced osteopenia in patients with rheumatic diseases. Arthritis Rheum 1985; 28: 361–8PubMedCrossRefGoogle Scholar
- 90.Reid IR, Evans MC, Wattie DH, et al. Bone mineral density of the proximal femur and lumbar spine in glucocorticoid treated patients. Osteoporos Int 1992; 2: 103–5PubMedCrossRefGoogle Scholar
- 91.Gluck DS, Murphy WA, Hahn TJ, et al. Bone loss in adults receiving alternate day glucocorticoid therapy: a comparison with daily therapy. Arthritis Rheum 1981; 24: 892–8PubMedCrossRefGoogle Scholar
- 92.Conference Report. Consensus development conference: diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 1993; 94: 646–50CrossRefGoogle Scholar
- 93.Greenwald M, Brandhi D, Spector T, et al. Corticosteroid-induced osteoporosis: effects of a treatment with slow-release sodium fluoride. Osteoporos Int 1992; 2: 303–4PubMedCrossRefGoogle Scholar
- 94.Bijlsma JWJ, Raymakers JA, Mosch C, et al. Effect of oral calcium and vitamin D on glucocorticoid-induced osteopenia. Clin Exp Rheumatol 1988; 6: 113–9PubMedGoogle Scholar
- 95.Reid IR, Ibbertson HK. Calcium supplements in the prevention of steroid induced osteoporosis. Am J Clin Nutr 1986; 44: 287–90PubMedGoogle Scholar
- 96.Sambrook P, Birmingham J, Kelly P, et al. Prevention of corticosteroid osteoporosis. A comparison of calcium, calcitriol and calcitonin. N Engl J Med 1993; 328: 1747–52PubMedCrossRefGoogle Scholar
- 97.Meunier PJ. Is steroid-induced osteoporosis preventable? N Engl J Med 1993; 328: 1781–2PubMedCrossRefGoogle Scholar
- 98.Ringe JD, Welzel D. Salmon calcitonin in the therapy of corticoid-induced osteoporosis. Eur J Clin Pharmacol 1987; 33: 35–9PubMedCrossRefGoogle Scholar
- 99.Studd J, Savvas M, Johnson M. Correction of corticosteroid-induced osteoporosis by percutaneous hormone implants. Lancet 1990; 2: 850–1Google Scholar
- 100.Reid IR, King AR, Alexander CJ, et al. Prevention of steroid-induced osteoporosis with bisphosphonate APD. Lancet 1988; 1: 143–6PubMedCrossRefGoogle Scholar
- 101.Skingle SJ, Crisp AJ. Increased bone density in patients on steroids with etidronate. Lancet 1994; 344: 543–4PubMedCrossRefGoogle Scholar
- 102.Adachi JD, Cranney A, Goldsmith CH, et al. Intermittent cyclic therapy with etidronate in the prevention of corticosteroid induced bone loss. J Rheumatol 1994; 21: 1922–6PubMedGoogle Scholar
- 103.Montecucco C, Caporali R, Caprotti P, et al. Sex hormones and bone metabolism in postmenopausal rheumatoid arthritis treated with two different glucocorticoids. J Rheumatol 1992; 19: 1895–900PubMedGoogle Scholar
- 104.Messina OD, Barreia JC, Zanchetta JR, et al. Effect of low doses of deflazacort vs prednisone on bone mineral content in premenopausal rheumatoid arthritis. J Rheumatol 1992; 19: 1520–6PubMedGoogle Scholar