Diagnostic Considerations
In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:
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Chronic infection
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Drug reactions
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Other rheumatologic diseases
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Infiltrative diseases
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HIV infection
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Neutropenia with large granular lymphocytosis (LGL), also known as pseudo-Felty syndrome
The last of these is a particular concern. LGL is a chronic leukemia characterized by a clonal expansion of cytotoxic T cells bearing the CD16 and CD57 markers. The large granular lymphocytes may occur in both the periphery and the bone marrow. LGL is an unusual entity that occurs in fewer than 1% of patients with rheumatoid arthritis (RA). It usually develops at the onset of RA, whereas FS occurs later in the disease course. The sex incidence is equal, and the severity of the underlying RA is less marked.
Neutropenia may occur in conjunction with a normal or increased total white blood cell (WBC) count. Thrombocytopenia, anemia, and splenomegaly may occur. In some situations, differentiation from FS may require immunophenotype analysis. Therapy for LGL is rarely necessary.
Somatic STAT3 and STAT5B mutations have been discovered in 30-40% of patients LGL, and a study of 14 patients with Felty syndrome by Savola et al found somatic STAT3 mutations in six of them (43%), but no STAT5B mutations. In addition, plasma cytokine profiling showed that 10 of the 92 assayed cytokines were elevated both in Felty syndrome and LGL. These authors concluded that unified re-classification of Felty syndrome and LGL is warranted. [9]
Differential Diagnoses
