Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Rheumatoid nodules

INTRODUCTION

The rheumatoid nodule is the most common cutaneous manifestation of rheumatoid arthritis (RA) [1,2]. Although nodules commonly are found on pressure points (such as the olecranon process), they may occur at other sites including ones within internal organs of the body. Thus, bedridden patients can develop nodules on the occiput and ischial areas, and nodules occasionally form on the Achilles tendon, and vocal cords [3]. Rheumatoid "nodulosis" is characterized by multiple nodules on the hands and multiple subchondral bone cysts known as "geodes" [4].

The clinical and histopathologic features, diagnosis, and treatment of rheumatoid nodules will be reviewed here. The articular features and an overview of the systemic and nonarticular manifestations of RA are presented separately. (See "Clinical features of rheumatoid arthritis" and "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis".)

PREVALENCE AND CLINICAL SIGNIFICANCE

Subcutaneous nodules — Palpable nodules in the subcutaneous tissues are present in 20 to 35 percent of patients with RA, and almost all nodule formers have positive tests for rheumatoid factor [1]; early data suggest that many patients with rheumatoid nodules have a positive test for antibodies to citrulline containing peptides (eg, anti-CCP) [5].

In many cases the nodules are neither symptomatic nor a cosmetic concern. However, rheumatoid nodules can be painful, disfiguring, interfere with function, or cause compressive neuropathies. Some patients find the nodules more distressing than the arthritis. The nodules may also ulcerate and thus serve as a site for local infection, or other distant infectious complications by hematogenous spread of bacteria.

A poorly understood phenomenon is that some patients treated for RA with methotrexate have a noticeable increase in the size and number of rheumatoid nodules. This is referred to as accelerated nodulosis and is discussed in more detail elsewhere. (See "Major side effects of low-dose methotrexate", section on 'Nodulosis'.)
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2009 UpToDate, Inc.
References Top
  1. Sayah, A, English JC, 3rd. Rheumatoid arthritis: a review of the cutaneous manifestations. J Am Acad Dermatol 2005; 53:191.
  2. Highton, J, Hessian, PA, Stamp, L. The Rheumatoid nodule: peripheral or central to rheumatoid arthritis?. Rheumatology (Oxford) 2007; 46:1385.
  3. Ylitalo, R, Heimburger, M, Lindestad, PA. Vocal fold deposits in autoimmune disease--an unusual cause of hoarseness. Clin Otolaryngol Allied Sci 2003; 28:446.
  4. Ginsberg, MH, Genant, HK, Yu, TF, et al. Rheumatoid nodulosis: An unusual variant of rheumatoid disease. Arthritis Rheum 1975; 18:49.
  5. Kim, SK, Park, SH, Shin, IH, Choe, JY. Anti-cyclic citrullinated peptide antibody, smoking, alcohol consumption, and disease duration as risk factors for extraarticular manifestations in Korean patients with rheumatoid arthritis. J Rheumatol 2008; 35:995.
  6. Walker, WC, Wright, V. Pulmonary lesions and rheumatoid arthritis. Medicine (Baltimore) 1968; 47:501.
  7. Yousem, SA, Colby, TV, Carrington, CB. Lung biopsy in rheumatoid arthritis. Am Rev Respir Dis 1985; 131:770.
  8. Watson, P, Simler, N, Screaton, N, Lillicrap, M. Management of accelerated pulmonary nodulosis following etanercept therapy in a patient with rheumatoid arthritis. Rheumatology (Oxford) 2008; 47:928.
  9. Horvath, IF, Szanto, A, Csiki, Z, et al. Intrapulmonary rheumatoid nodules in a patient with long-standing rheumatoid arthritis treated with leflunomide. Pathol Oncol Res 2008; 14:101.
  10. Rozin, A, Yigla, M, Guralnik, L, et al. Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy. Clin Rheumatol 2006; 25:384.
  11. Walters, MN, Ojeda, VJ. Pleuropulmonary necrobiotic rheumatoid nodules. A review and clinicopathological study of six patients. Med J Aust 1986; 144:648.
  12. Highton, J, Hung, N, Hessian, P, Wilsher, M. Pulmonary rheumatoid nodules demonstrating features usually associated with rheumatoid synovial membrane. Rheumatology (Oxford) 2007; 46:811.
  13. Kitas, G, Banks, MJ, Bacon, PA. Cardiac involvement in rheumatoid disease. Clin Med 2001; 1:18.
  14. Wislowska, M, Sypula, S, Kowalik, I. Echocardiographic findings and 24-h electrocardiographic Holter monitoring in patients with nodular and non-nodular rheumatoid arthritis. Rheumatol Int 1999; 18:163.
  15. Ahern, M, Lever, JV, Cosh, J. Complete heart block in rheumatoid arthritis. Ann Rheum Dis 1983; 42:389.
  16. Chatzis, A, Giannopoulos, N, Baharakakis, S, et al. Unusual cause of a stroke in a patient with seronegative rheumatoid arthritis. Cardiovasc Surg 1999; 7:659.
  17. Mounet, FS, Soula, P, Concina, P, Cerene, A. A rare case of embolizing cardiac tumor: rheumatoid nodule of the mitral valve. J Heart Valve Dis 1997; 6:77.
  18. Kang, H, Baron, M. Embolic complications of a mitral valve rheumatoid nodule. J Rheumatol 2004; 31:1001.
  19. Palmer, DG, Hogg, N, Highton, J, et al. Macrophage migration and maturation within rheumatoid nodules. Arthritis Rheum 1987; 30:728.
  20. Athanasou, NA, Quinn, J, Woods, CG, Mcgee, JO. Immunohistology of rheumatoid nodules and rheumatoid synovium. Ann Rheum Dis 1988; 47:398.
  21. Miyasaka, N, Sato, K, Yamamoto, K, et al. Immunological and immunohistochemical analysis of rheumatoid nodules. Ann Rheum Dis 1989; 48:220.
  22. Wikaningrum, R, Highton, J, Parker, A, et al. Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient. Arthritis Rheum 1998; 41:1783.
  23. Harris, ED Jr. A collagenolytic system produced by primary cultures of rheumatoid nodule tissue. J Clin Invest 1972; 51:2973.
  24. Stamp, LK, Easson, A, Lehnigk, U, et al. Different T cell subsets in the nodule and synovial membrane: absence of interleukin-17A in rheumatoid nodules. Arthritis Rheum 2008; 58:1601.
  25. Hessian, PA, Highton, J, Kean, A, et al. Cytokine Profile of the rheumatoid nodule suggests that it is a Th1 granuloma. Arthritis Rheum 2003; 48:334.
  26. Edwards, JC, Wilkinson, LS, Pitsillides, AA. Palisading cells of rheumatoid nodules: comparison with synovial intimal cells. Ann Rheum Dis 1993; 52:801.
  27. Elewaut, D, De Keyser, F, De Wever, N, et al. A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers. Ann Rheum Dis 1998; 57:480.
  28. Kato, H, Yamakawa, M, Ogino, T. Complement mediated vascular endothelial injury in rheumatoid nodules: a histopathological and immunohistochemical study. J Rheumatol 2000; 27:1839.
  29. Gorman, JD, David-Vaudey, E, Pai, M, et al. Lack of association of the HLA-DRB1 shared epitope with rheumatoid nodules: an individual patient data meta-analysis of 3,272 Caucasian patients with rheumatoid arthritis. Arthritis Rheum 2004; 50:753.
  30. Cronstein, BN, Eberle, MA, Gruber, HE, Levin, RI. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci U S A 1991; 88:2441.
  31. Merrill, JT, Shen, C, Schriebman, D, et al. Adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes. Arthritis Rheum 1997; 40:1308.
  32. Nyhall-Wahlin, BM, Jacobsson, LT, Petersson, IF, Turesson, C. Smoking is a strong risk factor for rheumatoid nodules in early rheumatoid arthritis. Ann Rheum Dis 2006; 65:601.
  33. Schofield, JK, Cerio, R, Grice, K. Systemic lupus erythematosus presenting with 'rheumatoid nodules'. Clin Exp Dermatol 1992; 17:53.
  34. Hassikou, H, Le Guilchard, F, Lespessailles, E, et al. Rheumatoid nodules in systemic lupus erythematosus: a case report. Joint Bone Spine 2003; 70:234.
  35. Simons, FE, Schaller, JG. Benign rheumatoid nodules. Pediatrics 1975; 56:29.
  36. Mastboom, WJ, van der, Staak FH, Festen, C, Postma, MH. Subcutaneous rheumatoid nodules. Arch Dis Child 1988; 63:662.
  37. McGrath, MH, Fleischer, A. The subcutaneous rheumatoid nodule. Hand Clin 1989; 5:127.
  38. Patatanian, E, Thompson, DF. A review of methotrexate-induced accelerated nodulosis. Pharmacotherapy 2002; 22:1157.
  39. Ching, DW, Petrie, JP, Klemp, P, et al. Injection therapy of superficial rheumatoid nodules. Br J Rheumatol 1992; 31:775.
white circle LOG IN
white circle DEMO