Felty's Syndrome
The most likely diagnosis is Felty's syndrome, characterized by the classic triad of long-standing rheumatoid arthritis, neutropenia, and splenomegaly in this patient with severe, destructive seropositive RA. 1, 2
Clinical Presentation Confirming the Diagnosis
This patient demonstrates all the pathognomonic features of Felty's syndrome:
- Long-standing, severe RA with destructive joint changes (swan-neck and boutonnière deformities, plantar subluxation of metatarsal heads) despite treatment with prednisone and etanercept 2
- Neutropenia with absolute neutrophil count of 345/mm³ (15% of 2300 WBC/mm³), which is severe and predisposes to bacterial infections like the E. coli bacteremia she developed 2
- Splenomegaly on physical examination 1, 2
- Subcutaneous rheumatoid nodules, indicating severe extra-articular disease manifestations typical of Felty's syndrome 2
Key Diagnostic Features
The bone marrow biopsy showing hypercellularity with lack of mature neutrophils is characteristic of Felty's syndrome, where neutropenia results from both decreased granulopoiesis and increased peripheral destruction of granulocytes 2. This distinguishes it from other causes of neutropenia where the marrow might be hypocellular or infiltrated.
Over 95% of Felty's syndrome patients are rheumatoid factor positive, and the syndrome typically occurs in patients with severe, long-standing RA who have significant extra-articular manifestations 2. The presence of destructive arthritis with nodules in this patient strongly supports this diagnosis.
Clinical Context and Complications
- Recurrent bacterial infections are the hallmark complication of Felty's syndrome due to severe neutropenia, as demonstrated by this patient's E. coli bacteremia from a urinary source 2
- The normocytic anemia (hemoglobin 9.2 mg/dL, MCV 88 fL) and thrombocytopenia (platelet count 132,000/mm³) are consistent with Felty's syndrome, which can present with pancytopenia 3, 4
- Moderate or absent joint inflammation contrasting with severe joint destruction is characteristic of Felty's syndrome, though this patient still has active symptoms 2
Important Pitfalls to Avoid
Do not confuse Felty's syndrome with large granular lymphocyte (LGL) leukemia, which can present similarly with neutropenia, splenomegaly, and RA. Approximately 30% of Felty's syndrome patients have LGL expansion, but the bone marrow biopsy showing hypercellularity with lack of mature neutrophils (rather than lymphocytic infiltration) helps distinguish Felty's syndrome 2. The bone marrow biopsy in this case specifically excluded malignancy by showing granulopoietic arrest rather than lymphocytic infiltration.
Consider that etanercept itself can cause hematologic abnormalities, including rare cases of pancytopenia and aplastic anemia 5. However, the constellation of long-standing severe RA, splenomegaly, subcutaneous nodules, and the specific bone marrow findings of hypercellularity with granulopoietic arrest point definitively to Felty's syndrome rather than drug-induced cytopenia.
Treatment Implications
The persistence of neutropenia and anemia after successful treatment of the infection confirms this is not simply infection-related bone marrow suppression but rather the underlying Felty's syndrome 2. Disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, are the most effective treatment for Felty's syndrome neutropenia, with the widest clinical experience 2. Abatacept has also shown efficacy in recent case reports for treating Felty's syndrome when methotrexate fails 4.