Lymphopenia in early arthritis: Impact on diagnosis and 3-year outcomes (ESPOIR cohort)

In patients with early arthritis naive to disease-modifying antirheumatic drugs, we evaluated the prevalence of initial and persistent lymphopenia, underlying diagnoses, and risk of infection or malignancy.

Eight hundred and thirteen patients with early arthritis included in the ESPOIR cohort had a clinical examination, laboratory tests (viral serology, immunological tests, and cytokine profile), and radiographs. We determined the prevalence of lymphopenia at baseline and after 3 years, associated factors, diagnoses, and risk of infection or malignancy.

At baseline, 50/813 (6.2%) patients had lymphopenia. Lymphopenia was associated with positive rheumatoid factor (P=0.02), cytopenia (P≤0.05), hepatitis C (P=0.05), higher C-reactive protein and DAS28 (P≤0.05 for both). Cytokine profile and radiological progression were not significantly different between patients with and without lymphopenia. Suspected diagnoses at inclusion were rheumatoid arthritis (RA, n=27), unclassified arthritis (n=15), systemic lupus erythematosus (SLE, n=3), spondyloarthritis (n=2), Sjögren's syndrome (n=1), hematologic disease (n=1), and fibromyalgia (n=1). Fifteen patients out of 42 (35.7%) with initial lymphopenia had persistent lymphopenia after 3 years, including 5 with documented causes (lupus, hepatitis C, undernutrition, azathioprine, and tamoxifen); none had PVB19, HIV, or HBV infection and none experienced infections, solid or hematologic malignancies during follow-up. Final diagnoses in these 15 patients were RA (n=6), unclassified arthritis (n=6), SLE (n=1), spondyloarthritis (n=1), and fibromyalgia (n=1).

Lymphopenia is rare in early arthritis. The most common rheumatic cause is RA, in which marked inflammation and other cytopenias are common. Lymphopenia in early arthritis is often short-lived, even when methotrexate is prescribed.