Felty Syndrome · What Is It, Causes, Symptoms, and More

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).   

RA is a chronic inflammatory disorder that most often causes progressive destruction of the joints, but can also present with extra-articular manifestations, including fatigue, muscle weakness, firm bumps of tissue on the skin, inflammation of the blood vessel walls, and interstitial lung disease. 

Overall, Felty syndrome typically affects individuals between 50-70 years of age and is about three times more common in those assigned female at birth. Felty syndrome occurs in less than 1-3% of individuals with rheumatoid arthritis, and with the growing use of more effective treatments for RA, its incidence 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, which is 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, 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.  

Although the exact cause remains unclear, research suggests that Felty syndrome occurs in a specific subset of individuals with rheumatoid arthritis, most commonly those who have had RA for more than 10 years and who present with a more aggressive form of the disorder.  

Along with the characteristic joint symptoms of RA, individuals with Felty syndrome also experience decreased immune response to recurrent bacterial infections, like those caused by Staphylococcus aureus or Pseudomonas aeruginosa. These infections typically affect the skin, mouth, and respiratory tract and can become quite severe, potentially leading to widespread infections and sepsis. 

Additionally, some individuals may experience non-specific signs of chronic inflammation, such as fever, fatigue, weakness, and loss of appetite. Discoloration of the skin, swollen lymph nodes, and enlargement of the liver may also be present. Inflammation of the blood vessel walls (i.e., vasculitis) can occur and potentially produce non-healing sores, or ulcers, on the skin of the lower limbs. In rare cases, individuals may develop symptoms associated with other autoimmune diseases; for example, dry mouth or dry eyes associated with Sjögren syndrome. 

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 specific laboratory tests, including 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 used to evaluate the size of the spleen.  

Finally, a bone marrow biopsy may be performed when needed to distinguish Felty syndrome from other disorders, such as non-Hodgkin lymphoma and large granular lymphocyte (LGL) leukemia. LGL leukemia, also known as pseudo-Felty syndrome, is a form of chronic leukemia that affects lymphocytes, a group of white blood cells. Like Felty syndrome, LGL leukemia may also develop in individuals with a history of long-standing RA and it is characterized by persistent neutropenia, recurrent bacterial infections, and splenomegaly. Distinguishing between these two conditions can be very challenging, and it may require a thorough evaluation by experienced pathologists and hematologists. 

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.  

In cases where conventional DMARDs are not effective, biological therapies such as TNF-alpha inhibitors, rituximab, and tocilizumab may be recommended. These medications target specific components of the immune system to better control inflammation associated with RA. Additionally, most of these medications also increase white blood cell count and minimize splenomegaly, thereby strengthening the immune system’s ability to fight infections. Other treatments, such as granulocyte colony-stimulating factor (G-CSF), may be prescribed to manage neutropenia specifically in severe cases.   

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.