What Is It, Causes, Symptoms, and More
Author: Anna Hernández, MD
Editors: Alyssa Haag, Józia McGowan, DO, FACOI, FNAOME, CS
Illustrator: Abbey Richard
Copyeditor: Joy Mapes
What is 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 3 times more common in individuals who were assigned female sex at birth. Felty syndrome occurs in less than 1-3% 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.
Is Felty syndrome fatal?
In general, individuals with Felty syndrome have a poorer prognosis than those without extra-articular manifestations (i.e., symptoms that are not joint-related) of RA. This is in part due to the involvement of neutropenia, which is characterized by an unusually low number of neutrophils, a specific type of white blood cells that play an essential role in defending the body against bacterial infections. Due to the lower white blood cell count, a person with Felty syndrome is more vulnerable to severe and recurrent bacterial infections and subsequent life-threatening complications (e.g., widespread infection and organ failure). Moreover, individuals with Felty syndrome may have an increased risk of developing certain types of cancer, such as non-Hodgkin’s lymphoma and other hematological malignancies.
What causes Felty syndrome?
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, 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.Regardless of the exact source of Felty syndrome, research has confirmed that Felty syndrome occurs in a subset of individuals who have RA, particularly those who have had the condition for more than 10 years and those who present with a more aggressive form of the disorder. 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 (i.e., rheumatoid nodules), inflammation of the blood vessel walls, and disorders of the lung tissue (e.g., interstitial lung disease).
What are the signs and symptoms of 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.Additionally, some individuals may experience non-specific signs of inflammation, such as fever, fatigue, weakness, and loss of appetite. Discoloration of the skin, swollen lymph nodes, and enlargement of the liver (i.e., hepatomegaly) may also present. Additionally, 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, the dry mouth or dry eyes associated with Sjögren’s syndrome.
How is Felty syndrome diagnosed?
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.Finally, a bone marrow biopsy may be performed when needed to distinguish Felty syndrome from other disorders, such as non-Hodgkin’s lymphoma and large granular lymphocyte (LGL) leukemia. LGL leukemia, also known as pseudo-Felty syndrome, is a type of chronic leukemia that affects lymphocytes, a group of white blood cells. Like Felty syndrome, LGL leukemia may also present 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 may require a thorough evaluation by experienced pathologists and hematologists.
How is Felty syndrome treated?
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.
What are the most important facts to know about Felty syndrome?
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.
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Resources for research and reference
National Organization for Rare Disorders (NORD). (2006). Felty syndrome. In Rare Disease Database. Retrieved March 31, 2021, from https://rarediseases.org/rare-diseases/felty-syndrome
Liu, X., & Loughran, T., Jr. (2011). The spectrum of large granular lymphocyte leukemia and Felty's syndrome. Current Opinion in Hematology, 18(4): 254-259. DOI: 10.1097/MOH.0b013e32834760fb
Narváez, J., Domingo-Domenech, E., Gómez-Vaquero, C., López-Vives, L., Estrada, P., Aparicio, M., Martín-Esteve, I., & Nolla, J. M. (2012). Biological agents in the management of Felty’s syndrome: A systematic review. Seminars in Arthritis and Rheumatism, 41(5): 658-668. DOI: 10.1016/j.semarthrit.2011.08.008
Owlia, M. B., Newman, K., & Akhtari, M. (2014). Felty's syndrome, insights and updates. The Open Rheumatology Journal, 8: 129-136. DOI: 10.2174/1874312901408010129Rozin, A., Hoffman, R., Hayek, T., & Balbir-Gurman, A. (2013). Felty’s syndrome without rheumatoid arthritis? Clinical Rheumatology, 32(5): 701-704. DOI: 10.1007/s10067-012-2157-3