Working Diagnosis:
Seronegative rheumatoid arthritis

Treatment:
Following initial right knee aspiration and corticosteroid injection, the patient returned with a left knee effusion requiring similar treatment.

Given recurrent bilateral effusions, he was referred to Rheumatology, where initiation of disease-modifying antirheumatic drug (DMARD) therapy was recommended. The patient initially deferred hydroxychloroquine and elected to continue with repeat aspirations as needed. However, due to increasing frequency of recurrent effusions, he ultimately agreed to begin DMARD therapy.

Outcome:
At seven weeks, the patient demonstrated full, pain-free range of motion, a normal gait, and no edema or tenderness to palpation.

He was counseled regarding limiting repeated oral corticosteroid tapers and was advised to use nabumetone as first-line oral therapy for future swelling episodes. He was instructed to continue follow-up with Rheumatology and return as needed for symptomatic flares.

Author's Comments:
In young patients with no significant medical or family history, bilateral knee pain and swelling warrant a broad differential diagnosis. While musculoskeletal conditions are common, it is important to consider systemic and inflammatory etiologies in cases without a known injury mechanism.1

This case highlights the importance of maintaining non-mechanical diagnoses within the differential diagnosis, as this represents a subtle early presentation of seronegative rheumatoid arthritis. The clinical history, physical examination, laboratory testing, and imaging evaluation assisted in excluding alternative diagnoses and facilitated timely Rheumatology referral. Early diagnosis and treatment remain critical to limiting disease progression and preventing irreversible joint damage.

Editor's Comments:
This case highlights the importance of maintaining a broad differential diagnosis when evaluating a common musculoskeletal complaint such as knee pain and effusion. Although serologic testing is frequently used in the evaluation of inflammatory arthritis, negative serologies should not exclude consideration of rheumatoid arthritis when the clinical presentation remains suspicious.

Seronegative rheumatoid arthritis can present a significant diagnostic challenge, even for experienced clinicians. It has been estimated that approximately 20-30% of patients with rheumatoid arthritis are seronegative, and these patients often present at a younger age with less clearly defined disease features.3 Recognition of persistent inflammatory symptoms, recurrent joint effusions, and elevated inflammatory markers can help prompt timely rheumatology referral and initiation of disease-modifying therapy.

Early identification of seronegative rheumatoid arthritis provides an opportunity to begin disease-modifying antirheumatic drug therapy earlier in the disease course, which has been associated with improved long-term outcomes and reduced risk of progressive joint damage.2,3

References:
1. Bunt CW, Jonas CE, Chang JG. Knee Pain in Adults and Adolescents: The Initial Evaluation. Am Fam Physician. 2018 Nov 1;98(9):576-585. PMID: 30325638.
2. van der Linden MP, le Cessie S, Raza K, van der Woude D, Knevel R, Huizinga TW, van der Helm-van Mil AH. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum. 2010 Dec;62(12):3537-46. doi: 10.1002/art.27692. PMID: 20722031.
3. Bugatti S, De Stefano L, Gandolfo S, Ciccia F, Montecucco C. Autoantibody-Negative Rheumatoid Arthritis: Still a Challenge for the Rheumatologist. The Lancet Rheumatology, 2023; 5, e743-e755

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