Felty syndrome

DEFINITION: Triad of (1) rheumatoid arthritis, (2) splenomegaly, and (3) neutropenia (ANC usually <2000/µL, often <1000/µL). It is a rare extra-articular manifestation of RA (<1% of patients).

EPIDEMIOLOGY/RISK FACTORS: Usually occurs in long-standing (>10 years), severe, erosive, seropositive RA (high-titer RF, often anti-CCP+). Strong association with HLA-DR4 (HLA-DRB1*04). More common in white patients and in those with other extra-articular disease (nodules, vasculitis). Often with female predominance, as with RA.

PATHOPHYSIOLOGY: Neutropenia is multifactorial: (a) autoantibodies and immune complexes bind neutrophils, causing peripheral destruction/margination; (b) impaired granulopoiesis in the marrow (autoantibodies, T-cell mediated suppression); (c) splenic sequestration/destruction (though splenectomy does not always correct neutropenia). Expansion of large granular lymphocytes (LGL, CD8+ T cells) is frequently seen, and Felty syndrome overlaps with T-cell LGL leukemia.

CLINICAL FEATURES: Features of active RA (deforming arthritis, rheumatoid nodules) plus splenomegaly, recurrent bacterial infections (skin, respiratory tract), leg ulcers, lymphadenopathy, weight loss, hepatomegaly, and skin pigmentation. Arthritis may be quiescent when neutropenia develops. Other cytopenias (anemia, thrombocytopenia) can occur. Nodular regenerative hyperplasia of the liver can cause portal hypertension.

LABS: Neutropenia, high RF, anti-CCP+, ANA often positive, antihistone antibodies, hypergammaglobulinemia, and elevated ESR. Bone marrow can show myeloid hyperplasia or maturation arrest.

DIAGNOSIS: Clinical: RA + splenomegaly + neutropenia after excluding other causes (drugs such as methotrexate, SLE, lymphoma, LGL leukemia, infection).

TREATMENT: Treat the underlying RA with DMARDs. Methotrexate is the usual first-line agent. Other options include rituximab, azathioprine, cyclosporine, and G-CSF (for severe neutropenia with infection). Splenectomy is reserved for refractory cases, such as recurrent infections despite therapy. Treat infections promptly with antibiotics.

COMPLICATIONS/PROGNOSIS: Serious bacterial infections are the main cause of morbidity and mortality. Increased risk of lymphoma.

BOARD PEARLS: - RA + splenomegaly + neutropenia = Felty. - Think HLA-DR4 and high-titer RF. - Mnemonic: "Felty = Fever (infections), Enlarged spleen, Low neutrophils, Tender/swollen joints, Young at heart (RA)" - or simply remember the triad. - Differentiate from: SLE (cytopenias, but no deforming erosive arthritis), Sjögren (dry eyes/mouth), Caplan syndrome (RA + pneumoconiosis with pulmonary nodules), and Still disease (systemic juvenile/adult-onset with fever, rash, hyperferritinemia).