Felty's syndrome

Felty's syndrome, also called Felty syndrome, (FS)[1] is rare autoimmune disease characterized by the triad of rheumatoid arthritis, enlargement of the spleen and too few neutrophils in the blood. The condition is more common in those aged 50–70 years, specifically more prevalent in females than males, and more so in Caucasians than those of African descent. It is a deforming disease that causes many complications for the individual.[2][3]

Felty's syndrome
SpecialtyRheumatology 

Signs and symptoms

The symptoms of Felty's syndrome are similar to those of rheumatoid arthritis. Patients suffer from painful, stiff, and swollen joints, most commonly in the joints of the hands, feet, and arms. In some affected individuals, Felty's syndrome may develop during a period when the symptoms and physical findings associated with rheumatoid arthritis have subsided or are not present; in this case, Felty's syndrome may remain undiagnosed. In more rare instances, the development of Felty's syndrome may precede the development of the symptoms and physical findings associated with rheumatoid arthritis.

Felty's syndrome is also characterized by an abnormally enlarged spleen (splenomegaly) and abnormally low levels of certain white blood cells (neutropenia). As a result of neutropenia, affected individuals are increasingly susceptible to certain infections. Keratoconjunctivitis sicca may occur due to secondary Sjögren's syndrome. Individuals with Felty's syndrome may also experience fever, weight loss, and/or fatigue. In some cases, affected individuals may have discoloration (abnormal brown pigmentation) of the skin, particularly of the leg, sores (ulcers) on the lower leg, and/or an abnormally large liver (hepatomegaly). In addition, affected individuals may have abnormally low levels of circulating red blood cells (anemia), a decrease in circulating blood platelets that assist in blood clotting functions (thrombocytopenia), abnormal liver function tests and/or inflammation of the blood vessels (vasculitis).[4]

Complications

Causes

The cause of Felty's syndrome is unknown, but it has been found to be more common in those with chronic rheumatoid arthritis. Some patients share the HLA-DR4 serotype. This syndrome is mostly present in people having extra articular manifestations of rheumatoid arthritis. People with this syndrome are at risk of infection because they have a low white blood cell count.[5]

Mechanism

The underlying pathogenesis of Felty's syndrome is not clear.

Rheumatoid Arthritis
A 65 year old patient with rheumatoid arthritis displaying swan neck deformity.

Rheumatoid arthritis is an autoimmune disease that is characterized by inflammation of the synovial joints due to attack by the body's own immune system. In this condition, the white blood cells travel through the blood stream to the synovial joints and release pro-inflammatory cytokines upon arrival. The result of this chemical release causes the synovial cells to release harmful chemicals in response as well as begin the growth of new blood vessels, forming a pannus. The pannus receives blood supply from the newly formed vessels and grows inward, invading the articular cartilage and bone within the joint. The damage to the once healthy tissue causes inflammation and ultimately fluid build-up in the joint. An accumulation of fluid results and the joints swell, slowly decreasing the space that keeps the bones from touching. If this condition is not treated, the joint space will completely narrow, causing ankylosis. At the advanced stage of ankylosis, joint mobility is completely occluded. Early presentation is commonly seen in the joints of hands and of the feet. As the disease progresses it can be seen in the knees, wrists, hips, and shoulders. This condition can affect and damage several other body systems such as the eyes, heart, lungs, and blood vessels.[6]

Rheumatoid arthritis is a condition that cannot be cured but symptoms can be treated using certain medications alone or in conjunction. Due to the increased inflammatory response of the body's immune system, this condition can cause a reduction in red and white blood cells.[7]

Neutropenia

In Felty's syndrome, chronic activation of neutrophils progresses to neutropenia and unabated infections.[8] Neutropenia is a decreased concentration of neutrophils in the blood. Neutrophils are the most abundant cells among white blood cells and play an important role in the immune system by destroying bacteria via phagocytosis. Inflammatory chemicals draw neutrophils to the area where they congregate and fight infection. A decrease in the number of neutrophils stimulates an autoimmune response which leads to arthritis. The loss and destruction of neutrophils leading to neutropenia is therefore, inflammation-driven due to the body's need for the immune response.[8]

Splenomegaly

Splenomegaly is a condition of the spleen causing it to be enlarged. The splenic condition involving Felty syndrome is more specifically noted as inflammatory splenomegaly. The spleen is an important lymphatic organ that is involved in filtration of the blood by discarding old and damaged red blood cells as well as maintaining platelet levels. The spleen is a lymphatic organ, which means it is largely involved in the immune system and immune responses. When the spleen becomes enlarged, it is a strong sign of infection somewhere in the body, and can be caused by inflammatory conditions such as rheumatoid arthritis. The increased need for production assistance of white blood cells to affected areas causes hyperfunction of the spleen. This increase in defense activities ultimately causes hypertrophy of the spleen, leading to splenomegaly.[9] The spleen is found in the left upper quadrant (LUQ) of the peritoneal cavity and due to its enlargement, can cause stress on neighboring organs.

Diagnosis

This condition affects less than 1% of patients with rheumatoid arthritis.[10] The presence of three conditions: rheumatoid arthritis, an enlarged spleen (splenomegaly), and an abnormally low white blood cell count are indications that Felty's syndrome is possibly occurring. This condition as a whole is difficult to diagnose due to its complexity given a combination of disorders. It is commonly overlooked or misdiagnosed as other conditions (e.g., leukemia, systemic lupus erythrematosus)[3] because of the rarity and lack of good understanding about it. An acronym can be used to make recognizing this disease somewhat easier:

S: Splenomegaly

A: Anemia

N: Neutropenia

T: Thrombocytopenia

A: Arthritis (rheumatoid)

Conditions of the Blood

A complete blood count (CBC) can be done to diagnose anemia (normochromic, normocytic), thrombocytopenia, and neutropenia.[11] Abnormal liver function tests are commonly used to help in diagnosis as the spleen and liver are strongly affected by one another.

Splenomegaly

If rheumatoid arthritis is present and other symptoms occur that are not commonly found within RA itself, such as a palpable spleen, further testing should be done. A palpable spleen is not always a clinical significance, therefore CT scan, MRI, or ultrasound can be administered in order to help diagnose the condition. According to Poulin et al, dimensional guidelines for diagnosing splenomegaly are as follows:[12]

  • Moderate if the largest dimension is 11–20 cm
  • Severe if the largest dimension is greater than 20 cm

Rheumatoid Arthritis

RA in patients with Felty's syndrome is chronic (after 10–15 years), and presents with increased severity along with extra articular manifestations.[8] RA can be mistaken for other conditions such as gout if not clinically diagnosed. Diagnosis can be confirmed by use of X-rays or synovial fluid analysis.[13]

Treatment

There is no real treatment for Felty's syndrome, rather the best method in management of the disease is to control the underlying rheumatoid arthritis. Immunosuppressive therapy for RA often improves granulocytopenia and splenomegaly; this finding reflects the fact that Felty's syndrome is an immune-mediated disease. A major challenge in treating FS is recurring infection caused by neutropenia. Therefore, in order to decide upon and begin treatment, the cause and relationship of neutropenia with the overall condition must be well understood.[8] Most of the traditional medications used to treat RA have been used in the treatment of Felty's syndrome. No well-conducted, randomized, controlled trials support the use of any single agent. Most reports on treatment regimens involve small numbers of patients.[14]

Splenectomy may improve neutropenia in severe disease.

Use of rituximab[15] and leflunomide[16] have been proposed.

Use of gold therapy has also been described.[17][18]

Prognosis

Prognosis is dependent on the severity of symptoms and the patient's overall health.

History

The condition was named after its founder Augustus Roi Felty (1895-1964), after the doctor reportedly saw 5 patients in 1924 with a combination of conditions never before documented. The presence of chronic arthritis, splenomegaly, and leucopenia in all 5 patients prompted him to use his name to define the unknown syndrome.[8]

See also

References
  1. Online Mendelian Inheritance in Man (OMIM): 134750
  2. Balint GP, Balint PV (Oct 2004). "Felty's syndrome". Best Pract Res Clin Rheumatol. 18 (5): 631–645. doi:10.1016/j.berh.2004.05.002. PMID 15454123.
  3. Woolston, W 2017, 'Felty's Syndrome: A Qualitative Case Study', MEDSURG Nursing, vol. 26, no. 2, pp. 105-118.
  4. "CIGNA – Felty's Syndrome". Retrieved 2008-11-07.
  5. "HowStuffWorks "Felty's Syndrome – Medical Dictionary"". Retrieved 2008-11-07.
  6. "Rheumatoid arthritis - Symptoms and causes - Mayo Clinic". www.mayoclinic.org. Retrieved 2017-12-13.
  7. "Rheumatoid Arthritis". Nucleus Medical Media. November 4, 2017.
  8. Dwivedi, N., & Radic, M. (2012). Neutrophil activation and B-cell stimulation in the pathogenesis of Felty's syndrome. Polskie Archiwum Medycyny Wewnetrznej, 122(7-8), 374-379.
  9. Radhakrishnan N, Sacher RA, Besa EC (Nov 12, 2017). "Splenomegaly: Etiology". MedScape.
  10. "Felty's Syndrome Causes, Symptoms, Diagnosis and Treatment by MedicineNet.com". Retrieved 2008-11-07.
  11. "Thrombocytopenia: Diagnosis". NHI; National Heart, Lung, and Blood Institute. Nov 12, 2017.
  12. Neetu Radhakrishnan (2019-10-20). "Splenomegaly". Medscape. Updated Apr. 2012 (referring the classification system to Poulin et al.
  13. Eggebeen AT (2007). "Gout: an update". Am Fam Physician. 76 (6): 801–8. PMID 17910294.
  14. Keating, Richard M. "eMedicine – Felty's Syndrome". Retrieved 2008-11-07.
  15. Chandra PA, Margulis Y, Schiff C (2008). "Rituximab is useful in the treatment of Felty's syndrome". Am J Ther. 15 (4): 321–2. doi:10.1097/MJT.0b013e318164bf32. PMID 18645332. S2CID 29359015.
  16. Talip F, Walker N, Khan W, Zimmermann B (April 2001). "Treatment of Felty's syndrome with leflunomide". J. Rheumatol. 28 (4): 868–70. PMID 11327265.
  17. Michael S. Clement (1 June 2007). Blueprints Q & As for step 2. Lippincott Williams & Wilkins. pp. 71–. ISBN 978-0-7817-7820-6. Retrieved 14 November 2010.
  18. Almoallim H, Klinkhoff A (January 2005). "Longterm outcome of treatment of Felty's syndrome with intramuscular gold: case reports and recommendations for management". J. Rheumatol. 32 (1): 20–6. PMID 15630719.
Classification
External resources
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