Background
Felty syndrome (FS), which was first described in 1924, is a potentially serious condition that is associated with seropositive (rheumatoid factor [RF]–positive) rheumatoid arthritis (RA).[1] Felty syndrome is characterized by the triad of RA, splenomegaly, and granulocytopenia. Although many patients with Felty syndrome are asymptomatic, some develop serious and life-threatening infections secondary to granulocytopenia.
For additional information on rheumatoid arthritis, see Medscape’s Rheumatoid Arthritis Resource Center.
Pathophysiology
Although the pathophysiology of Felty syndrome is not fully understood, evidence points to splenic sequestration and subsequent granulocyte destruction. Studies performed almost 50 years ago demonstrated lower granulocyte counts in the splenic vein compared with those in the splenic artery. Researchers have shown immune complexes coating granulocytes, diminished granulocyte growth factor levels, and numerous circulating autoantibodies, including those against granulocyte surface antigens. T-cell large granular lymphocyte leukemia (TLGL) and Felty syndrome share overlapping pathophysiologic features.[2]
In 2002, a study in Germany examined 15 patients with neutropenia due to Felty syndrome and matched them to a control group of 16 patients with normocytic RA. In addition, 16 patients with neutropenia and systemic lupus erythematosus (SLE) were matched to a control group of 16 patients with SLE. Antibodies against granulocyte colony-stimulating factor (G-CSF) were measured. Eleven patients with Felty syndrome demonstrated anti–G-CSF immunoglobulin G (IgG); none of the patients in the RA control group demonstrated anti–G-CSF IgG. Six patients with both neutropenia and SLE and 6 patients in the SLE control group also had anti–G-CSF antibodies. These antibodies appeared to have a neutralizing effect on G-CSF.[3]
Epidemiology
Frequency
United States
Felty syndrome affects approximately 1-3% of all patients diagnosed with RA, and RA occurs in about 1% of the general population. The true prevalence of Felty syndrome is difficult to ascertain because many affected patients are asymptomatic. Felty syndrome is rare in children. The prevalence of Felty syndrome may be decreasing with the advent of more potent antirheumatic agents. It seems to be quite rare in the African American population.
International
Few data suggest that the international frequency of Felty syndrome differs from that of the United States.
Mortality/Morbidity
Although many individuals with Felty syndrome are asymptomatic, others progress and develop life-threatening infections. Pulmonary and skin infections are common. The level of debilitation due to the underlying RA, along with the extent of immunosuppression used in treating both RA and Felty syndrome, heavily influence mortality and morbidity. One study from southwest England observed 32 patients with Felty syndrome; 5 patients died of overwhelming bronchopneumonia during a mean follow-up period of 5.2 years. Curiously, in the past 20 years in the United States, the frequency of hospitalization for rheumatoid vasculitis and ultimate splenectomy in patients with Felty syndrome has dropped, possibly because of earlier and more aggressive treatment of RA, controlling the disease before the manifestations of Felty syndrome appear.
Race
Felty syndrome is most common in whites and is uncommon in blacks. The human leukocyte antigen DR4 (HLA-DR4) genotype, which is a marker for more aggressive RA and more frequent extra-articular manifestations in whites, is strongly associated with Felty syndrome.
Sex
Felty syndrome is more common in females, with an approximate female-to-male ratio of 3:1. Underreporting and asymptomatic cases cause difficulty in determining the true sex ratio.
Age
Felty syndrome is most common during the fifth through the seventh decades of life. The condition is usually associated with more than 10 years of preceding RA activity. Men are affected with Felty syndrome earlier in the course of RA than women are.
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