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Clinicopathologic features of rheumatoid nodules: a retrospective analysis

  • Seongsik Bang
  • Yeseul Kim
  • Kiseok Jang
  • Seung Sam Paik
  • Su-Jin ShinEmail author
Original Article
  • 38 Downloads

Abstract

Objectives

The clinical and histopathologic features of patients that have been diagnosed with rheumatoid nodules were investigated.

Methods

This study included patients with rheumatoid nodules, confirmed by histologic assessment, between 2005 and 2018 at the Hanyang University Hospital. Each patient had a total score of 6 or more according to the American College of Rheumatology criteria.

Results

A total of 57 cases were included in this study. The median age of the patients at the time of diagnosis was 57 years (range, 39–70 years). The average duration between the onset of treatment and occurrence of rheumatoid nodule was 11.6 years. Bone erosion was observed in 44 patients (77.2%). Among 57 patients, 56 (98.2%) were treated with disease-modifying anti-rheumatic drugs; most of the patients (87.7%) showed high-positive rheumatoid factor or high-positive anti-citrullinated protein antibodies. The foot, hand, and wrist, in order of decreasing frequencies, were the anatomical sites with the highest occurrence of rheumatoid nodules, whereas, the soft tissue adjacent to the joint, subcutis, dermis, lung parenchyma, and submucosal layer of the supraglottic area, also in an order of highest frequency, were the histological sites with the highest occurrence. Microscopically, central necrobiosis was present in all cases. Stromal fibrosis (96.5%), palisading of histiocytes (82.5%), perivascular lymphocytic infiltration (68.4%), and cleft or cystic degeneration (63.2%) were also observed.

Conclusions

A clinicopathological review of cases diagnosed with rheumatoid nodules histologically was performed to confirm characteristics that can help clinicians understand the pathophysiology of the condition and make accurate diagnoses of rheumatoid nodules.

Key Points

• We reviewed the clinical, imaging, and histologic features of rheumatoid nodule.

• The average duration between the onset of treatment and occurrence of rheumatoid nodule was 11.6 years.

• Among 57 rheumatoid nodule patients, 98.2% were treated with disease-modifying anti-rheumatic drugs.

Keywords

Rheumatoid nodule Rheumatoid nodules Rheumatoid noduloses Rheumatoid nodulosis 

Notes

Author contributions

Seong Sik Bang: assessment of the special staining slides; review of histological material; data analysis; drafting of the manuscript; preparation of the illustrations; preparation of the final text

Yeseul Kim: assessment of the immunohistochemical slides; review of histological material; preparation of the final text

Kiseok Jang: provided clinical data; preparation of the final text

Seung Sam Paik: provided clinical data; preparation of the final text

Su-Jin Shin: elaboration of the research concept; review of histological material; choice of cases for the study; general supervision of the study; drafting of the manuscript and preparation of the final text

Funding

This work was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2017R1C1B5017930).

Compliance with ethical standards

The Institutional Review Board of the Hanyang University Hospital (HYUH 2018-10-006) approved the study and waived the requirement for informed consent.

Disclosures

None.

Supplementary material

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References

  1. 1.
    Tilstra JS, Lienesch DW (2015) Rheumatoid nodules. Dermatol Clin 33(3):361–371.  https://doi.org/10.1016/j.det.2015.03.004 CrossRefGoogle Scholar
  2. 2.
    Ziff M (1990) The rheumatoid nodule. Arthritis Rheum 33(6):761–767CrossRefGoogle Scholar
  3. 3.
    Patterson JW (1988) Rheumatoid nodule and subcutaneous granuloma annulare. A comparative histologic study. Am J Dermatopathol 10(1):1–8CrossRefGoogle Scholar
  4. 4.
    Stamp LK, Easson A, Lehnigk U, Highton J, Hessian PA (2008) Different T cell subsets in the nodule and synovial membrane: absence of interleukin-17A in rheumatoid nodules. Arthritis Rheum 58(6):1601–1608.  https://doi.org/10.1002/art.23455 CrossRefGoogle Scholar
  5. 5.
    Miyasaka N, Sato K, Yamamoto K, Goto M, Nishioka K (1989) Immunological and immunohistochemical analysis of rheumatoid nodules. Ann Rheum Dis 48(3):220–226.  https://doi.org/10.1136/ard.48.3.220 CrossRefGoogle Scholar
  6. 6.
    Knoess M, Krukemeyer MG, Kriegsmann J, Thabe H, Otto M, Krenn V (2008) Colocalization of C4d deposits/CD68+ macrophages in rheumatoid nodule and granuloma annulare: immunohistochemical evidence of a complement-mediated mechanism in fibrinoid necrosis. Pathol Res Pract 204(6):373–378.  https://doi.org/10.1016/j.prp.2008.01.009 CrossRefGoogle Scholar
  7. 7.
    Nyhall-Wahlin BM, Turesson C, Jacobsson LT, Nilsson JA, Forslind K, Albertsson K, Ronnelid J, Petersson IF (2011) The presence of rheumatoid nodules at early rheumatoid arthritis diagnosis is a sign of extra-articular disease and predicts radiographic progression of joint destruction over 5 years. Scand J Rheumatol 40(2):81–87.  https://doi.org/10.3109/03009742.2010.509103 CrossRefGoogle Scholar
  8. 8.
    Matsushita I, Uzuki M, Matsuno H, Sugiyama E, Kimura T (2006) Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis. Mod Rheumatol 16(6):401–403.  https://doi.org/10.1007/s10165-006-0522-2 CrossRefGoogle Scholar
  9. 9.
    Horvath IF, Szanto A, Csiki Z, Szodoray P, Zeher M (2008) Intrapulmonary rheumatoid nodules in a patient with long-standing rheumatoid arthritis treated with leflunomide. Pathol Oncol Res 14(1):101–104.  https://doi.org/10.1007/s12253-008-9003-6 CrossRefGoogle Scholar
  10. 10.
    Braun MG, Van Rhee R, Becker-Capeller D (2004) Development and/or increase of rheumatoid nodules in RA patients following leflunomide therapy. Z Rheumatol 63(1):84–87.  https://doi.org/10.1007/s00393-004-0537-z CrossRefGoogle Scholar
  11. 11.
    Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69(9):1580–1588.  https://doi.org/10.1136/ard.2010.138461 CrossRefGoogle Scholar
  12. 12.
    Traistaru MR, Kamal D, Trasca DM, Foarfa MC, Gruia CL, Rogoveanu OC (2016) Rheumatoid nodules and quality of life in rheumatoid arthritis females - complex assessment. Romanian J Morphol Embryol 57(1):215–225Google Scholar
  13. 13.
    Ziemer M, Muller AK, Hein G, Oelzner P, Elsner P (2016) Incidence and classification of cutaneous manifestations in rheumatoid arthritis. J Dtsch Dermatol Ges 14(12):1237–1246.  https://doi.org/10.1111/ddg.12680 Google Scholar
  14. 14.
    Houlder EL, Millier MJ, Highton J, Gwynne-Jones D, Stamp LK, Hessian PA (2017) Expression of the genes facilitating methotrexate action within subcutaneous rheumatoid nodules. Clin Exp Rheumatol 35(6):943–947Google Scholar
  15. 15.
    Soukup T, Dosedel M, Nekvindova J, Antonin Kubena A, Tacheci I, Duintjer Tebbens J, Vlcek J, Bradna P, Barvik I, Pavek P (2017) The plausible association of MTHFR and ADORA2A polymorphisms with nodules in rheumatoid arthritis patients treated with methotrexate. Pharmacogenet Genomics 27(2):43–50.  https://doi.org/10.1097/FPC.0000000000000256 CrossRefGoogle Scholar
  16. 16.
    Wikaningrum R, Highton J, Parker A, Coleman M, Hessian PA, Roberts-Thompson PJ, Ahern MJ, Smith MD (1998) 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 41(10):1783–1797.  https://doi.org/10.1002/1529-0131(199810)41:10<1783::AID-ART10>3.0.CO;2-W CrossRefGoogle Scholar
  17. 17.
    Koslow M, Young JR, Yi ES, Baqir M, Decker PA, Johnson GB, Ryu JH (2019) Rheumatoid pulmonary nodules: clinical and imaging features compared with malignancy. Eur Radiol 29(4):1684–1692.  https://doi.org/10.1007/s00330-018-5755-x CrossRefGoogle Scholar
  18. 18.
    Chaganti S, Joshy S, Hariharan K, Rashid M (2013) Rheumatoid nodule presenting as Morton’s neuroma. J Orthop Traumatol 14(3):219–222.  https://doi.org/10.1007/s10195-012-0215-x CrossRefGoogle Scholar
  19. 19.
    Jagpal A, Navarro-Millan I (2018) Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment and treatment. BMC Rheumatol 2:10.  https://doi.org/10.1186/s41927-018-0014-y CrossRefGoogle Scholar
  20. 20.
    Gualtierotti R, Ughi N, Marfia G, Ingegnoli F (2017) Practical management of cardiovascular comorbidities in rheumatoid arthritis. Rheumatol Ther 4(2):293–308.  https://doi.org/10.1007/s40744-017-0068-0 CrossRefGoogle Scholar
  21. 21.
    Urman A, Taklalsingh N, Sorrento C, McFarlane IM (2018) Inflammation beyond the joints: rheumatoid arthritis and cardiovascular disease. Scifed J Cardiol 2(3)Google Scholar
  22. 22.
    Turesson C, McClelland RL, Christianson TJ, Matteson EL (2007) Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 66(1):70–75.  https://doi.org/10.1136/ard.2006.052506 CrossRefGoogle Scholar
  23. 23.
    Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE (2005) Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum 52(3):722–732.  https://doi.org/10.1002/art.20878 CrossRefGoogle Scholar
  24. 24.
    Mastboom WJ, van der Staak FH, Festen C, Postma MH (1988) Subcutaneous rheumatoid nodules. Arch Dis Child 63(6):662–664.  https://doi.org/10.1136/adc.63.6.662 CrossRefGoogle Scholar
  25. 25.
    Gurer G, Faruk Sendur O, Tasci Bozbas G (2006) Benign rheumatoid nodules in childhood. Pediatr Int 48(1):94–96.  https://doi.org/10.1111/j.1442-200X.2006.02166.x CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Departments of Pathology, College of MedicineHanyang UniversitySeoulRepublic of Korea

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