Skip to main content
SpringerLink
Log in

Drug-Induced Rheumatic Disorders

Incidence, Prevention and Management

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

The purpose of this article is to review the causes, the clinical manifestations and the management of the more frequent drug-induced rheumatic disorders. These include: (i) articular and periarticular manifestations induced by fluoroquinolones, nonsteroidal anti-inflammatory drugs, injections of corticosteroids, and retinoids; (ii) multisystemic manifestations such as drug-induced lupus and arthritis induced by vaccination, Bacillus Calmette-Guérin therapy and cytokines; (iii) drug-induced disorders of bone metabolism (corticosteroid-induced osteoporosis, drug-induced osteomalacia and osteonecrosis); and (iv) iatrogenic complex regional pain syndromes. Disorders caused by nonpharmacological and rarely used treatments have been deliberately excluded.

Knowledge of these drug-induced clinical symptoms or syndromes allows an earlier diagnosis and treatment, and earlier drug withdrawal if necessary. With the introduction of new medications such as the recombinant cytokines and antiretroviral treatments, the number of drug-induced rheumatic disorders is likely to increase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II

Similar content being viewed by others

References

  1. Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med 1991; 324: 384–94

    Article  PubMed  CAS  Google Scholar 

  2. Halkin H. Adverse effects of the fluoroquinolones. Rev Infect Dis 1988; 10Suppl. 1: S258–S261

    Article  PubMed  CAS  Google Scholar 

  3. Arcieri G, Griffith E, Gurenwaldt G, et al. Ciprofloxacine: an update on clinical experience. Am J Med 1987; 82: 381–6

    PubMed  CAS  Google Scholar 

  4. Lafon M. Tendinopathies et fluoroquinolones. Concours Med 1993; 115: 819–25

    Google Scholar 

  5. Lanoux P, Legin C, Reksa A, et al. Effets secondaires des fluoroquinolones. Etude rétrospective sur l’année 1992. Sem Hôp Paris 1993; 69: 1273–6

    Google Scholar 

  6. Gough A, Kasali O, Sigler R, et al. Quinolone arthropathy. Acute toxicity to immature articular cartilage. Toxicol Pathol 1992; 20(3): 436–50

    Article  PubMed  CAS  Google Scholar 

  7. Pertuiset E, Lenoir G, Jehanne M, et al. Tolérance articulaire de la péfloxacine et de l’ofloxacine chez les enfants et adolescents atteints de mucoviscidose. Rev Rheum 1989; 56: 735–40

    CAS  Google Scholar 

  8. Stahlmann R, Förster C, Van Sickle D. Quinolones in children. Are concerns over arthropathy justified? Drug Saf 1993; 9(6): 397–403

    Article  PubMed  CAS  Google Scholar 

  9. Chysky V, Kapila K, Hullman R. Safety of ciprofloxacin in children: world wide clinical experience based on compassionate use. Emphasis on joint evaluation. Infection 1991; 19: 329–32

    Article  Google Scholar 

  10. Pradhan K, Arora N, Jena A, et al. Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth. Acta Paediatr 1995; 84: 555–60

    Article  PubMed  CAS  Google Scholar 

  11. Zabraniecki L, Negrier I, Vergne P, et al. Fluoroquinolone induced tendinopathy: report of 6 cases. J Rheumatol 1996; 23: 516–20

    PubMed  CAS  Google Scholar 

  12. Chaslerie A, Bannwarth B, Landreau JM, et al. Ruptures tendineuses et fluoroquinolones: un effet indésirable de classe. Rev Rheum 1992; 59: 297–8

    CAS  Google Scholar 

  13. Koeger AC, Chaibi P, Roger B, et al. Apport de l’IRM dans les complications tendineuses des fluoroquinolones [abstract]. Rev Rheum 1993; 60: 752

    Google Scholar 

  14. Ronningen H, Langeland N. Indomethacin treatment in osteoarthritis of hip joint. Does the treatment interfere with the natural course of the disease. Acta Orthop Scand 1979; 50: 169–74

    Article  PubMed  CAS  Google Scholar 

  15. Rashad S, Revell P, Hemingway A, et al. Effect of non steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989; II: 519–22

    Article  Google Scholar 

  16. Watson M. Femoral-head height loss: a study of the relative significance of some of its determinants in hip degeneration. Rheumatol Rehabil 1976; 15: 264–9

    Article  PubMed  CAS  Google Scholar 

  17. Loyau G. Anti-inflammatoires non stéroïdiens et cartilage. In: Le cartilage articulaire: dégénérescence et possibilités de réparation. Paris: MSD, Sidem, 1984: 145–60

    Google Scholar 

  18. Lequesne M, Ray G. La coxopathie destructrice rapide idiopathique. Etude étiologique prospective de 27 cas. Rev Rhum 1989; 56: 115–9

    PubMed  CAS  Google Scholar 

  19. Brandt KD, Palmoski MJ. Effects of salicylates and other nonsteroidal anti-inflammatory drugs on articular cartilage. Am J Med 1984; 13: 65–9

    Article  Google Scholar 

  20. Palmoski MJ, Brandt KD. Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage. Arthritis Rheum 1980; 23: 1010–20

    Article  PubMed  CAS  Google Scholar 

  21. Palmoski MJ, Brandt KD. Effects of salicylate and indomethacin on glycosaminoglycan and prostaglandin E2 synthesis in intact canine knee cartilage ex vivo. Arthritis Rheum 1984; 27: 398–403

    Article  PubMed  CAS  Google Scholar 

  22. Del Favero A. Dangers of long-term use of NSAIDs in osteoarthritis. In: Aronson JK, Van Boxtel CJ, editors. Side effects of drugs annual. 18th ed. Amsterdam: Elsevier, 1994: 87–8

    Google Scholar 

  23. Ito A, Nose T, Takahashi S, et al. Cyclooxygenase inhibitors augment the production of pro-matrix metalloproteinase 9 (progelatinase B) in rabbit articular chondrocytes. FEBS Lett 1995; 360: 75–9

    Article  PubMed  CAS  Google Scholar 

  24. Jolly W, Whittem T, Jolly A, et al. The dose-related effects of phenylbutazone and a methylprednisolone acetate formulation (Depo-medrol) on cultured explants of equine carpal articular cartilage. J Vet Pharmacol Ther 1995; 18: 429–37

    Article  PubMed  CAS  Google Scholar 

  25. Erill S. Corticotrophins and corticosteroids. In: Aronson JK, Van Boxtel CJ, editors. Side effects of drugs annual. 18th ed. Amsterdam: Elsevier, 1994: 391

    Google Scholar 

  26. Parikh J, Houpt J, Jacobs S, et al. Charcot’s arthropathy of the shoulder following intraarticular corticosteroid injection. J Rheumatol 1993; 20: 885–7

    PubMed  CAS  Google Scholar 

  27. Verschure PJ, Van Der Kraan PM, Vitters EL, et al. Stimulation of proteoglycan synthesis by triamcinolone acetonide and insulin-like growth factor 1 in normal and arthritic murine articular cartilage. J Rheumatol 1994; 21: 920–6

    PubMed  CAS  Google Scholar 

  28. Roberts W, Babcock E, Breitbach S, et al. Corticosteroid injection in rheumatoid arthritis does not increase rate of total joint arthroplasty. J Rheumatol 1996; 23(6): 1001–4

    PubMed  CAS  Google Scholar 

  29. Pelletier JP, DiBattista J, Raynauld J, et al. The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis. Lab Invest 1995; 72(5): 578–88

    PubMed  CAS  Google Scholar 

  30. Caldwell JR. Intra-articular corticosteroids. Drugs 1996; 52(4): 507–14

    Article  PubMed  CAS  Google Scholar 

  31. Owen DS. Aspiration and injection of joints and soft tissues. In: Kelley WN, Harris ED, Ruddy S, et al., editors. Textbook of rheumatology, 4th ed. Philadelphia: Saunders Company, 1993: 545–61

    Google Scholar 

  32. Kaplan G, Haettich B. Rheumatological symptoms due to retinoids. Baillière’s Clin Rheumatol 1991; 5(1): 77–97

    Article  CAS  Google Scholar 

  33. Frame B, Jackson CE, Reynolds WA, et al. Hypercalcemia and skeletal effects in chronic hypervitaminosis A. Ann Intern Med 1974; 80: 44

    PubMed  CAS  Google Scholar 

  34. Freyria A, Ronzière M, Boutillon M, et al. Effects of retinoic acid on protein synthesis by foetal bovine chondrocytes in high-density culture: down-regulation of the glucose-regulated protein, GRP-78, and type II collagen. Biochem J 1995; 305: 391–6

    PubMed  CAS  Google Scholar 

  35. Kelley WN, Schumacher HR. Gout. In: Kelley WN, Harris ED, Ruddy S, et al., editors. Textbook of rheumatology, 4th ed. Philadelphia: Saunders Company, 1993: 1291–336

    Google Scholar 

  36. Bannwarth B. The drug-induced rheumatisms. Rev Rheum 1996; 63(10): 639–47

    CAS  Google Scholar 

  37. Scott JT. Drug-induced gout. Baillieres Clin Rheumatol 1991; 5(1): 39–60

    Article  PubMed  CAS  Google Scholar 

  38. Burack DA, Griffith BP, Thompson ME, et al. Hyperuricemia and gout among heart transplant recipients receiving cyclosporine. Am J Med 1992; 92: 141–6

    Article  PubMed  CAS  Google Scholar 

  39. Le Goff P, Saraux A. Induced lupus. Rev Rheum 1999; 66(1): 40–5

    Google Scholar 

  40. Fritzler MJ. Drugs recently associated with lupus syndromes. Lupus 1994; 3: 455–9

    Article  PubMed  CAS  Google Scholar 

  41. Yung RL, Richardson BC. Drug-induced lupus. Rheum Dis Clin North Am 1994; 20: 61–85

    PubMed  CAS  Google Scholar 

  42. Burlingame RW. The clinical utility of antihistone antibodies. Autoantibodies reactive with chromatin in systemic lupus erythematosus and drug-induced lupus. Clin Lab Med 1997; 17: 367–78

    PubMed  CAS  Google Scholar 

  43. Rubin RL, Bell SA, Burlingame RW. Autoantibodies associated with lupus induced by diverse drugs target a similar epitope in the (H2A-H2B)-DNA complexe. J Clin Invest 1992; 90: 165–73

    Article  PubMed  CAS  Google Scholar 

  44. Drouvalakis KA, Buchanan RBC. Phospholipid specificity of autoimmune and drug-induced lupus anticoagulants; association of phosphatidylethanolamine reactivity with thrombosis in autoimmune disease. J Rheumatol 1998; 25: 290–5

    PubMed  CAS  Google Scholar 

  45. Masson C, Chevailler A, Pascaretti C, et al. Minocycline related lupus. J Rheumatol 1996; 23: 2160–1

    PubMed  CAS  Google Scholar 

  46. Yung RL, Johnson KJ, Richardson BC. New concepts in the pathogenesis of drug-induced lupus. Lab Invest 1995; 73(6): 746–59

    PubMed  CAS  Google Scholar 

  47. Tingle AJ, Allen M, Petty RE, et al. Rubella-associated arthritis. 1. Comparative study of joint manifestations associated with natural rubella infection and RA 27/3 rubella immunisation. Ann Rheum Dis 1986; 45: 606–12

    Article  Google Scholar 

  48. Weibel RE, Benor DE. Chronic arthropathy and musculoskeletal symptoms associated with rubella vaccines. Arthritis Rheum 1996; 39(9): 1529–34

    Article  PubMed  CAS  Google Scholar 

  49. Ray P, Black MD, Shinefield H, et al. Risk of chronic arthropathy among women after rubella vaccination. JAMA 1997; 278(7): 551–6

    Article  PubMed  CAS  Google Scholar 

  50. Tingle AJ, Mitchell LA, Grace M, et al. Randomised double-bind placebo-controlled study on adverse effects of rubella immunisation in seronegative women. Lancet 1997; 349(3): 1277–81

    Article  PubMed  CAS  Google Scholar 

  51. Gross K, Combe C, Kruger K, et al. Arthritis after hepatitis B vaccination: report of three cases. Scand J Rheumatol 1995; 24: 50–2

    Article  PubMed  CAS  Google Scholar 

  52. Vautier G, Carty JE. Acute sero-positive rheumatoid arthritis occurring after hepatitis B vaccination. Br J Rheumatol 1994; 33: 991–8

    Article  PubMed  CAS  Google Scholar 

  53. Vinceneux P, Pouchot J, Lemaitre F, et al. Vaccinations et rhumatismes. In: Kahn MF, Kuntz D, Dryll A, et al, editors. Actualités rhumatologiques. Paris: Expansion Scientifique Française, 1996: 28–44

    Google Scholar 

  54. Maillefert JF, Sibilia J, Toussirot E, et al. Arthropathies après vaccin contre l’hépatite B. Rev Rheum 1998; 65Suppl. 5: S246–S247

    Google Scholar 

  55. Pope JE, Stevens A, Howson W, et al. The development of rheumatoid arthritis after recombinant hepatitis B vaccination. J Rheumatol 1998; 25: 1687–93

    PubMed  CAS  Google Scholar 

  56. Buchs N, Chevrel G, Miossec P. Bacillus Calmette-Guérin induced aseptic arthritis: an experimental model of reactive arthritis. J Rheumatol 1998; 25(9): 1662–4

    PubMed  CAS  Google Scholar 

  57. Pancaldi P, Van Linthoudt D, Alborino D, et al. Reiter’s syndrome after intravesical bacillus Calmette-Guérin treatment for superficial bladder carcinoma. Br J Rheumatol 1993; 32: 1096–8

    Article  PubMed  CAS  Google Scholar 

  58. Torisu M, Miyahara T, Shinohara N, et al. A new side effect of BCG immunotherapy: BCG-induced arthritis in man. Cancer Immunol Immunother 1978; 5: 77–83

    Article  Google Scholar 

  59. Pichert G, Jost LM, Zobeli L, et al. Thyroiditis after treatment with interleukin-2 and interferon alpha-2a. Br J Cancer 1990; 62: 100–4

    Article  PubMed  CAS  Google Scholar 

  60. Rönnblom LE, Alm GV, Öberg KE. Autoimmunity after alpha-interferon therapy for malignant carcinoid tumors. Ann Intern Med 1991; 115: 178–83

    PubMed  Google Scholar 

  61. Jumbou O, Berthelot JM, French N, et al. Polyarthritis during interferon alpha therapy: 3 cases and review of the literature. Eur J Dermatol 1995; 5: 581–4

    Google Scholar 

  62. Chazerain P, Meyer O, Ribard P. Trois cas de polyarthrite survenant au cours d’un traitement par interféron-alpha recombinant. Rev Rheum 1992; 59(5): 303–9

    CAS  Google Scholar 

  63. O’Connell PG, Gerber LH, DiGiovanna JJ, et al. Arthritis in patients with psoriasis treated with gamma-interferon. J Rheumatol 1992; 19: 80–2

    PubMed  Google Scholar 

  64. Massarotti EM, Liu NY, Mier J, et al. Chronic inflammatory arthritis after treatment with high-dose interleukin-2 for malignancy. Am J Med 1992; 92: 693–7

    Article  PubMed  CAS  Google Scholar 

  65. Vidarsson B, Geirsson AJ, Onundarson PT. Reactivation of rheumatoid arthritis and development of leukocytoclastic vasculitis in a patient receiving granulocyte colony-stimulating factor for Felty’s syndrome. Am J Med 1995; 98: 589–91

    Article  PubMed  CAS  Google Scholar 

  66. De Vries EGE, Willemse PHB, Biesma B, et al. Flare-up of rheumatoid arthritis during GM-CSF treatment after chemotherapy. Lancet 1991; 338: 517–8

    Article  PubMed  Google Scholar 

  67. Sambrook PN. Corticosteroid induced osteoporosis. J Rheumatol 1996; 23Suppl. 45: S19–S22

    Google Scholar 

  68. Gronowicz G, McCarthy MB. Glucocorticoids inhibit the attachment of osteoblasts to bone extracellular matrix proteins and decrease β-1 integrin levels. Endocrinology 1995; 136: 598–608

    Article  PubMed  CAS  Google Scholar 

  69. American College of Rheumatology task force on osteoporosis guidelines. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum 1996; 39 (11): 1791–801

    Google Scholar 

  70. Jones G, Sambrook PN. Drug-induced disorders of bone metabolism. Drug Saf 1994; 10(6): 480–9

    Article  PubMed  CAS  Google Scholar 

  71. Cosman F, Nieves J, Herbert J, et al. High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton. J Bone Miner Res 1994; 9: 1097–105

    Article  PubMed  CAS  Google Scholar 

  72. Zaqqa D, Jackson RD. Diagnosis and treatment of glucocorticoid-induced osteoporosis. Cleve Clin J Med 1999; 66(4): 221–30

    PubMed  CAS  Google Scholar 

  73. Saag KG, Emkey RD, Gruber B, et al. Alendronate for the management of glucocorticoid-induced osteoporosis: results of the multicenter U.S. study [abstract]. Arthritis Rheum 1997; 40: S136

    Google Scholar 

  74. Hall GM, Daniels M, Doyle DV, et al. The effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with or without steroids. Arthritis Rheum 1994; 37: 1499–505

    Article  PubMed  CAS  Google Scholar 

  75. Reid IR, Wattie DJ, Evans MC, et al. Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 1996; 156: 1173–7

    Article  PubMed  CAS  Google Scholar 

  76. Lems WF, Jacobs JW, Bijlsma JW, et al. Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid-induced osteoporosis? Ann Rheum Dis 1997; 56: 357–63

    Article  PubMed  CAS  Google Scholar 

  77. Rizzoli R, Chevalley T, Slosman DO, et al. Sodium monofluorophosphate increases vertebral bone mineral density in patients with corticosteroid-induced osteoporosis. Osteoporos Int 1995; 5: 39–46

    Article  PubMed  CAS  Google Scholar 

  78. Adachi JD, Bensen WG, Brown J, et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 1997; 337: 382–7

    Article  PubMed  CAS  Google Scholar 

  79. Cortet B, Hachulla E, Barton I, et al. Evaluation of the efficacy of etidronate therapy in preventing glucocorticoid-induced bone loss in patients with inflammatory rheumatic diseases. Rev Rheum 1999; 66(4): 214–9

    CAS  Google Scholar 

  80. Hahn TJ, Hendin BA, Scharp CR, et al. Serum 25-hydroxycalciferol levels and bone mass in children on chronic anticonvulsant therapy. N Engl J Med 1975; 292: 550–4

    Article  CAS  Google Scholar 

  81. Weinstein RS, Bryce GF, Sappington LJ, et al. Decreased serum ionized calcium and normal vitamin D metabolite levels with anticonvulsant drug treatment. J Clin Endocrinol Metab 1984; 58: 1003–9

    Article  PubMed  CAS  Google Scholar 

  82. Perry W, Erooga MA, Brown J, et al. Calcium metabolism during rifampicine and isoniazid therapy for tuberculosis. J R Soc Med 1982; 75: 533–6

    PubMed  CAS  Google Scholar 

  83. Woodson GC. An interesting case of osteomalacia due to antacid use associated with stainable bone aluminiumin a patient with normal renal function. Bone 1998; 22: 695–8

    Article  PubMed  CAS  Google Scholar 

  84. Jowsey J, Riggs BL, Kelly PJ, et al. The treatment of osteoporosis with disodium ethane-1-hydroxy-1, 1-diphosphonate. J Lab Clin Med 1971; 78: 574–84

    PubMed  CAS  Google Scholar 

  85. Boyce BF, Smith L, Fogelman I, et al. Focal osteomalacia due to low dose diphosphonate therapy in Paget’s disease. Lancet 1984; I: 821–4

    Article  Google Scholar 

  86. Miller P, Watts NB, Licata AA, et al. Cyclic etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven years of treatment. Am J Med 1997; 103: 468–76

    Article  PubMed  CAS  Google Scholar 

  87. Fleisch H. Bisphosphonates: mechanisms of action. Endocrin Rev 1998; 19: 80–100

    Article  CAS  Google Scholar 

  88. Schnitzler CM, Solomon L. Histomorphometric analysis of a calcaneal stress fracture: a possible complication of fluoride therapy for osteoporosis. Bone 1986; 7: 193–8

    Article  PubMed  CAS  Google Scholar 

  89. Steinberg ME, Steinberg DR. Osteonecrosis. In: Kelley WN, Harris ED, Ruddy S, et al., editors. Textbook of rheumatology, 4th ed. Philadelphia: Saunders Company, 1993: 1628–50

    Google Scholar 

  90. Ficat RP, Arlet J. In: Hungerford DS, editor. Ischemia and necrosis of the bone. Baltimore: Williams & Wilkins, 1980: 131–71

  91. Kenzora JE, Glimcher MJ. Accumulative cell stress: the multifactorial etiology of idiopathic osteonecrosis. Orthop Clin North Am 1985; 16: 667–70

    Google Scholar 

  92. Cruess RL. Osteonecrosis of bone: current concepts as to etiology and pathogenesis. Clin Orthop 1978; 130: 151–5

    Google Scholar 

  93. Good AE, Green RA, Zarafonetis CJ. Rheumatic symptoms during tuberculosis therapy. Ann Intern Med 1965; 63: 800–7

    PubMed  CAS  Google Scholar 

  94. Lequesne M, Moghtader R. L’algodystrophie de l’isoniazide et de l’éthionamide. Rev Rheum 1966; 33: 727–34

    CAS  Google Scholar 

  95. Zabraniecki L, Doub A, Mularczyk M, et al. Frozen shoulder: a new delayed complication of protease inhibitors therapy. Rev Rheum 1998; 65: 72–4

    CAS  Google Scholar 

  96. Léone J, Béguinot I, Dehlinger V, et al. Adhesive capsulitis of the shoulder induced by protease inhibitor therapy. Three new cases. Rev Rheum 1998; 65: 800–1

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology, CHU Dupuytren, 2 Avenue Martin Luther King, F-87042, Limoges Cedex, France

    Pascale Vergne, Phillipe Bertin, Christine Bonnet, Claire Scotto & Richard Trèves

Authors
  1. Pascale Vergne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Phillipe Bertin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine Bonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claire Scotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard Trèves
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pascale Vergne.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vergne, P., Bertin, P., Bonnet, C. et al. Drug-Induced Rheumatic Disorders. Drug-Safety 23, 279–293 (2000). https://doi.org/10.2165/00002018-200023040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200023040-00002

Keywords

Search

Navigation