Volume 3 - Issue 4

Monoarticular large joint arthritic presentation of rheumatoid arthritis - A case report

S. Chockalingam*, C. Arunkumar

Department of Orthopaedic Surgery, Kauvery Hospital, Trichy - Cantonment, India

*Correspondence: smch17@gmail.com

Abstract

Rheumatoid arthritis (RA) is a chronic, symmetrical, inflammatory arthritis that usually involves small joints. Mono articular arthritis involving a single large joint is not part of EULAR 2010 algorithm for the presentation of rheumatoid arthritis. Here we report a late diagnosis of large joint monoarticular rheumatoid arthritis presented to our department after two surgical procedures. Rheumatoid factor is often used as the serology test in RA. Our patient had positive anti-CCP but a negative rheumatoid factor. He responded to Disease Modifying Anti Rheumatic Drugs (DMARDs) with excellent clinical outcomes. This case highlights the importance of considering rheumatoid arthritis in a patient with monoarticular arthritis. It also illustrates the importance of doing anti-CCP tests as it helps to diagnose RA early.

Keywords: Monoarticular rheumatoid arthritis, Rheumatoid factor, Anti-CCP

Background

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that mainly involves articular inflammation. Around 0.5 to 1% of the population worldwide is affected by this disease, which results in joint destruction and disability [1]. Current treatment is based on aggressive anti-rheumatic therapy in the early phase of the disease and therefore, delays the disease progression [2]. Diagnosis is mainly based on serologic testing, in particular testing for rheumatoid factor (RF) and anti-cyclic citrullinated peptide(anti-CCP) antibody assay [3]. Mono articular large joint arthritis presentation is a rare entity, initially affecting large joints such as hips and knees, then progressing to a polyarticular presentation [4]. However, this presentation is not part of the EULAR criteria of rheumatoid arthritis presentations. Here we report a patient with monoarticular RA who presented to our outpatient clinic, for who a prompt diagnosis and treatment resulted in a good outcome.

Case Presentation

A 42-year-old male patient with a one-year history of pain and swelling in the right knee presented to our department with worsening of his symptoms. There was no history of trauma/fever/other joint involvement. Medical history included chronic kidney disease (CKD), on conservative treatment, and not on dialysis. He had undergone two surgeries in the right knee for the same complaints elsewhere before presenting to our department.

The initial surgery was arthroscopic subtotal synovectomy with decompression and the second surgery was open total synovectomy with joint lavage. Physical examination of the right knee showed midline healthy scar, moderate effusion, warmth, and joint line tenderness associated with restriction in flexion up to 100 degrees (Fig. 1). Laboratory work-up from the outside hospital showed elevated levels of ESR and CRP, with normal RF. Our hospital laboratory workup showed elevated ESR, anti-CCP, with normal RF (Table 1). MRI was done from the outside hospital before two surgeries revealed knee effusion with synovial thickening and osteochondritis dissecans medial femoral condyle (Fig. 2). However, the surgical procedures failed to confirm this diagnosis, thus leaving us to diagnose the condition.

We diagnosed his condition as monoarticular RA and started on methotrexate, sulfasalazine, and hydroxychloroquine. He showed marked improvement in his symptoms. He is maintaining his improvement achieved with DMRADs.

Monoarticular large joint arthritic presentation

Fig. 1. Clinical image of patient's knee joint.

Monoarticular large joint arthritic presentation

Fig. 2. MRI sagittal and coronal images of patient's right knee joint.

Table 1. Laboratory reports from outside and our hospital

Outside Hospital

Our Hospital

ESR 120 mm/h CRP 12.9 mg/dL

ESR 129mm/h

RA factor 10 IU/ml

RA factor <10 IU/ml

Anti-CCP 86.2 U/ml

Discussion

The differential diagnosis of chronic inflammatory monoarticular arthritis includes infections, crystal arthropathies, autoimmune diseases such as arthritis due to seronegative spondylarthritis, and to a lesser extent RA. The possible etiologies of non-inflammatory monoarthritis include pigmented villonodular synovitis, single joint osteoarthritis, and neuropathic arthropathy [4].

Rheumatoid arthritis is a common symmetrical chronic inflammatory arthritis with a worldwide prevalence of up to 1% [5]. The 2010 ACR/EULAR criteria for definite RA consists of a point-based system that includes four domains: confirmed synovitis in more than one joint (higher scores are assigned by a higher number of small joints involved) (0-5), presence of RA antibodies [rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP)] (0-3), elevated acute phase reactants [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] (0-1), and symptom duration of 6 weeks or longer (0-1) [6]. A score of ≥ 6 is needed for recognizing the presence of a diagnosis of RA. Though the 2010 ACR/EULAR criteria are helpful in classifying the RA presentation, they do not include monoarticular RA, and patients who do not meet the score of ≥6.

Monoarticular RA is a rare entity, that initially affects large joints and then progresses to polyarticular presentation within 3-5 years [7,8]. Untreated RA can result in both short- and long-term complications with an increase in mortality and morbidity. A study by Allaire S et al., reports that 35% of patients with RA had disability 10 years after diagnosis [9]. Hence it is essential to diagnose rheumatoid arthritis even when a presentation is at the monoarticular stage.

Around 70-80% of patients with RA are positive for autoantibodies such as rheumatoid factors (RFs) and anti-citrullinated protein antibodies (ACPAs) [10]. High levels of serum RF indicate increased disease activity, radiographic progression, and the presence of extra-articular manifestations. However, RF is not very specific, can also be detected in other rheumatic disorders, infections as well as in normal healthy individuals. The sensitivity of RF is 50-90%, and specificity is 50-95% [2,11].

Anti-CCP antibodies are more specific markers than RF. They are present at the very beginning of the disease or even years before the first symptoms. Anti-CCP antibodies are autoantibodies directed against citrullinated proteins in the synovium of RA patients. High levels of serum anti-CCPs indicate poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%. A study by Chang et al., assessed the sensitivity and specificity of RF and anti-CCP in RA patients and found out anti-CCP is more sensitive and specific than RF [12] (Table 2). New immunologic markers include anti- carbamylated protein antibodies (anti-CarP) and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33) [11,13].

Table 2. Sensitivity, specificity, PPV and NPV reported by Chang et al [12].

Autoantibodies

Sensitivity
(%)

Specificity
(%)

Positive Predictive
Value (PPV) (%)

Negative Predictive
Value (NPV) (%)

RF

67

79

37

93

Anti-CCP

79

98

86

96

Early diagnosis, initiation of prompt treatment, and a close follow-up aiming at remission, should be regarded as the standard of care in the management of RA [14]. Disease-modifying anti-rheumatic drugs (DMARDs) are the first-line drugs used in the treatment of RA. They target inflammation and thereby further prevent joint damage. DMARDs greatly improve disease symptoms and prevent disease progression in RA patients.

The available DMARDs are subdivided into

  1. Conventional synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine)
  2. Targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors)
  3. Biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules [15].

It is important to start DMARDs in rheumatoid arthritis patients for maximum benefit. Even though our patient did not fit in with the EULAR 2010 presentations of RA, we were able to start DMRADs with excellent relief of symptoms. Thus, the criteria should be used to classify the presentations of Rheumatoid arthritis and not to diagnose the disease.

Conclusion

Mono articular large joint arthritis does not fit in with EULAR 2010 criteria for presentations of RA. Mono articular arthritis is however very common in clinical practice. It is important to rule out other causes of monoarticular arthritis and still consider Rheumatoid arthritis in the differential diagnosis.

Early diagnosis with appropriate investigations and aggressive treatment decreases the disease progression, improves the function of the joint, and increases the quality of life. This case report highlights the importance of Anti CCP in monoarticular arthritis in the early diagnosis of RA when other causes have been ruled out.

References

  1. Wu CY, Yang HY, Luo SF, et al. From rheumatoid factor to anti-citrullinated protein antibodies and anti-carbamylated protein antibodies for diagnosis and prognosis prediction in patients with rheumatoid arthritis. Int J Mol Sci. 2021;22(2):686.
  2. Vos I, Van Mol C, Trouw LA, et al. Anti-citrullinated protein antibodies in the diagnosis of rheumatoid arthritis (RA): diagnostic performance of automated anti-CCP-2 and anti-CCP-3 antibodies assays. Clin Rheumatol. 2017;36(7):1487-92.
  3. Demoruelle MK, Deane K. Antibodies to Citrullinated Protein Antigens (ACPAs): clinical and pathophysiologic significance. Curr Rheumatol Rep. 2011 Oct;13(5):421-30.
  4. Sarazin J, Schiopu E, Namas R. Case series: Monoarticular rheumatoid arthritis. Eur J Rheumatol. 2017;4(4):264-7.
  5. Firestein GS. KW, eds. Etiology and pathogenesis of rheumatoid arthritis. Philadelphia, Pa.: Saunders. Elsevier; 2009.
  6. Aletaha D, Neogi T, Silman AJ, et al. Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and Rheum. 2010;62(9):2569-81.
  7. Tanaka N, Yamada Y, Sakahashi H, et al. Predictors of rheumatoid arthritis in patients who have monoarthritis in a knee joint. Modern Rheumatol. 2001;11(1):61-4.
  8. Douraiswami BTS, Thanigai S. Monoarticular rheumatoid arthritis of the wrist: a rare entity. OA Case Rep. 2013;10:80.
  9. Allaire S, Wolfe F, Niu J, et al. Current risk factors for work disability associated with rheumatoid arthritis: recent data from a US national cohort. Arthritis Rheum. 2009 Mar 15; 61(3): 321-8.
  10. Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001.
  11. Matuszewska A, Madej M, Wiland P. Immunological markers of rheumatoid arthritis. Postepy Hig Med Dosw. 2016;70:251-7.
  12. Chang PY, Yang CT, Cheng CH, et al. Diagnostic performance of anti-cyclic citrullinated peptide and rheumatoid factor in patients with rheumatoid arthritis. Int J Rheum Dis. 2016;19(9):880-6.
  13. Sulaiman FN, Wong KK, Ahmad WAW, Ghazali WSW. Anti-cyclic citrullinated peptide antibody is highly associated with rheumatoid factor and radiological defects in rheumatoid arthritis patients. Medicine (Baltimore). 2019;98(12):e14945.
  14. Monti S, Montecucco C, Bugatti S, et al. Rheumatoid arthritis treatment: the earlier the better to prevent joint damage. RMD Open. 2015;1(Suppl 1):e000057.
  15. Lin YJ, Anzaghe M, Schülke S. Update on the Pathomechanism, diagnosis, and treatment options for rheumatoid arthritis. Cells. 2020;9(4):880.
Dr. S. Chockalingam

Dr. S. Chockalingam

Senior Consultant


Kauverian - Scientific Journals - Volume 1 - issue 1


Kauverian - Scientific Journals - Volume 1 - issue 2


Kauverian - Scientific Journals - Volume 1 - issue 3


Kauverian - Scientific Journals - Volume 1 - issue 4


Kauverian - Scientific Journals - Volume 1 - issue 5


Kauverian - Scientific Journals - Volume 1 - issue 6


Kauverian - Scientific Journals - Volume 1 - issue 7


Kauverian - Scientific Journals - Volume 1 - issue 8


Kauverian - Scientific Journals - Volume 1 - issue 9


Kauverian - Scientific Journals - Volume 2 - issue 1


Kauverian - Scientific Journals - Volume 2 - issue 2


Kauverian - Scientific Journals - Volume 2 - Issue 3


Kauverian - Scientific Journals - Volume 2 - Issue 4


Kauverian - Scientific Journals - Volume 2 - Issue 5


Kauverian - Scientific Journals - Volume 2 - Issue 6


Kauverian - Scientific Journals - Volume 2 - Issue 7


Kauverian - Scientific Journals - Volume 2 - Issue 8


Kauverian - Scientific Journals - Volume 2 - Issue 9


Kauverian - Scientific Journals - Volume 2 - Issue 10


Kauverian - Scientific Journals - Volume 2 - Issue 11


Kauverian - Scientific Journals - Volume 2 - Issue 12


Kauverian - Scientific Journals - Volume 3 - Issue 1


Kauverian - Scientific Journals - Volume 3 - Issue 2


Kauverian - Scientific Journals - Volume 3 - Issue 3


Kauverian - Scientific Journals - Volume 3 - Issue 4


Kauverian - Scientific Journals - Volume 3 - Issue 5


Kauverian - Scientific Journals - Volume 3 - Issue 6


Kauverian - Scientific Journals - Volume 3 - Issue 7


Kauverian - Scientific Journals - Volume 3 - Issue 8


Kauverian - Scientific Journals - Volume 3 - Issue 9


Kauverian - Scientific Journals - Volume 3 - Issue 10


Kauverian - Scientific Journals - Volume 3 - Issue 11-1


Kauverian - Scientific Journals - Volume 3 - Issue 11-2


Kauverian - Scientific Journals - Volume 3 - Issue 12


Kauverian - Scientific Journals - Volume 4 - Issue 1


Kauverian - Scientific Journals - Volume 4 - Issue 2


Kauverian - Scientific Journals - Volume 4 - Issue 3


Kauverian - Scientific Journals - Volume 4 - Issue 4


Kauverian - Scientific Journals - Volume 4 - Issue 5


Kauverian - Scientific Journals - Volume 4 - Issue 6


Kauverian - Scientific Journals - Volume 4 - Issue 7


Kauverian - Scientific Journals - Volume 4 - Issue 8


Kauverian - Scientific Journals - Volume 4 - Issue 9


Kauverian - Scientific Journals - Volume 5 - Issue 1


Kauverian - Scientific Journals - Volume 5 - Issue 2


Kauverian - Scientific Journals - Volume 5 - Issue 3


Kauverian - Scientific Journals - Volume 5 - Issue 4


Kauverian - Scientific Journals - Volume 5 - Issue 5


Kauverian - Scientific Journals - Volume 5 - Issue 6


Kauverian - Scientific Journals - Volume 5 - Issue 7


Kauverian - Scientific Journals - Volume 5 - Issue 8


Kauverian - Scientific Journals - Volume 5 - Issue 9


Kauverian - Scientific Journals - Volume 5 - Issue 10


Kauverian - Scientific Journals - Volume 5 - Issue 11


Kauverian - Scientific Journals - Volume 5 - Issue 12


Kauverian - Scientific Journals - Volume 5 - Issue 13

LOCATE US

Find a Doctor Teleconsultation Emergency