Felty Syndrome

Felty syndrome (FS) is a rare but potentially serious disorder characterized by the presence of three conditions: rheumatoid arthritis (RA), enlarged spleen (i.e., splenomegaly), and a low number of neutrophils (i.e., neutropenia). 

Overall, Felty syndrome is generally diagnosed in individuals between 50 to 70 years of age, and it is about three times more common in individuals who were assigned female sex at birth. Felty syndrome occurs in less than 1 to 3% of patients with rheumatoid arthritis, and with the growing use of more effective treatments for RA, the risk of developing Felty syndrome appears to be declining.

The exact cause of Felty syndrome is not completely understood. It likely involves multiple factors, including increased genetic susceptibility and autoimmunity (i.e., when the body’s immune system mistakenly attacks its own healthy cells, often for unknown reasons). Nearly all individuals with Felty syndrome have a specific genetic marker known as human leukocyte antigen DR4, or HLA-DR4, that increases the risk of developing extra-articular manifestations of rheumatoid arthritis. In these individuals, an autoimmune response against neutrophils may trigger the development of the neutropenia associated with Felty syndrome. 

Most individuals with Felty syndrome are asymptomatic, but others may present with signs and symptoms of rheumatoid arthritis, such as pain, swelling, stiffness, and loss of mobility in the affected joints. The most characteristic finding of Felty syndrome is decreased immune response to recurrent bacterial infections, like those caused by Staphylococcus aureus or Pseudomona aeruginosa. These infections typically affect the skin, mouth, and respiratory tract.

Felty syndrome is a clinical diagnosis that is generally suspected in individuals with a history of long-standing RA, splenomegaly, and a low white blood cell count. Although Felty syndrome is traditionally characterized by this classic triad of symptoms, severe joint involvement and splenomegaly are not always present and thus are no longer necessary for establishing the diagnosis. A physical examination may or may not reveal an enlarged spleen, joint deformities in the hands and fingers, swollen lymph nodes, or enlargement of the liver. 

In most cases, diagnosis is confirmed with additional tests, including testing for rheumatoid-arthritis-associated autoantibodies (e.g.,  rheumatoid factor or anti-CCP antibody) and a complete blood count to demonstrate neutropenia. Imaging techniques, such as an abdominal ultrasound or computerized tomography (CT) scan, may be employed to evaluate the size of the spleen. 

Treatment of Felty syndrome focuses on addressing the symptoms of rheumatoid arthritis and reducing the risk of life-threatening infections. Long-term management involves the use of disease-modifying antirheumatic medications (DMARDs), like methotrexate, hydroxychloroquine, and sulfasalazine. DMARDs can help suppress the inflammation associated with RA. Additionally, most of these medications increase white blood cell count and minimize splenomegaly, thereby strengthening the immune system’s ability to fight infections. Other medications, such as rituximab and granulocyte colony-stimulating factor (GCS-F), may be prescribed to manage neutropenia specifically. 

A splenectomy, or surgical removal of the spleen, may improve the course of Felty syndrome, but this is generally reserved for individuals who do not respond well to initial medical treatments. 

Finally, it is important to promptly identify and treat any infections to avoid further complications. Infection management generally involves treatment with broad-spectrum antibiotics, along with supportive measures.

Felty syndrome is a rare, potentially serious extra-articular manifestation of rheumatoid arthritis (RA) that is complicated by the presence of a low white blood cell count and an enlarged spleen (i.e., splenomegaly). The exact cause of Felty syndrome is unknown, but associated risk factors include severe, long-standing RA, increased genetic susceptibility, and autoimmunity. Although some individuals with Felty syndrome are asymptomatic, others can develop severe, life-threatening infections that typically affect the skin and respiratory tract. Treatment of Felty syndrome focuses on addressing the symptoms of rheumatoid arthritis with disease-modifying antirheumatic medications (DMARDs), which may also reduce the risk of developing severe infections. For individuals with severe neutropenia and recurrent infections despite medical treatment, surgical removal of the spleen may be an option.