Felty Syndrome

Overview

Felty syndrome is a rare but serious extra-articular manifestation of long-standing, seropositive rheumatoid arthritis (RA), characterized by the classic triad of RA, splenomegaly, and neutropenia. It was first described in 1924 by the US-American physician Augustus Roi Felty. It most commonly occurs after at least 10 years of poorly controlled RA and is associated with severe joint damage and extra-articular features. It predominantly affects middle-aged Caucasian women and may signal more aggressive disease. Occurs in <1% of patients with RA.

Anatomy and Physiology

• Spleen plays a role in immune surveillance and removal of aged/damaged blood cells; in Felty syndrome, it is enlarged due to lymphoid hyperplasia.
• Bone marrow and peripheral blood are critical in leukopoiesis and immune regulation; altered in Felty due to neutropenia and altered immune activity.

Aetiology and Risk Factors

Aetiology
• Autoimmune process driven by chronic RA
• T-cell mediated destruction or peripheral sequestration of neutrophils
• Immune complex deposition in spleen

Risk Factors
• Long-standing RA (>10 years)
• Seropositive RA (RF and anti-CCP positive)
• Caucasian ethnicity
• Female sex (F:M ratio ~3:1)
• Presence of HLA-DR4 allele

Pathophysiology

• Chronic RA leads to systemic inflammation and immune dysregulation
• Development of splenomegaly due to hyperplasia of lymphoid follicles and immune cell accumulation
• Neutropenia arises from splenic sequestration and immune-mediated destruction of neutrophils
• Reduced neutrophil count leads to increased susceptibility to infections, particularly skin and respiratory tract

Clinical Manifestations

• Features of RA: joint pain, swelling, stiffness, especially in small joints
• Splenomegaly: may be asymptomatic or present as fullness in the left upper quadrant
• Neutropenia: leads to recurrent infections — skin ulcers, pneumonia, sepsis
• Extra-articular RA features: anemia, thrombocytopenia, lymphadenopathy, leg ulcers, hepatomegaly
• Possible constitutional symptoms: fatigue, low-grade fever, weight loss

Diagnosis

Diagnostic criteria (clinical diagnosis based on classic triad; no universal criteria established):
• Known seropositive RA
• Absolute neutrophil count <2000/μL
• Splenomegaly on imaging or examination

Investigations
• FBC: neutropenia, anemia, thrombocytopenia
• ESR/CRP: elevated in active RA
• RF and anti-CCP: usually positive
• ANA: may be positive
• LFTs: mild elevation possible
• Bone marrow biopsy: to exclude myelodysplastic syndrome
• Imaging: ultrasound/CT showing splenomegaly
• Synovial fluid analysis (if effusion present)

Differential diagnoses

Treatment

Control RA inflammation:

• Consider lowering methotrexate dose initially (potential cause of neutropenia)
• Control RA with csDMARD and bDMARD: methotrexate, leflunomide
• bDMARDs: Rituximab or anti-TNF agents

Treat neutropenia:

• G-CSF (e.g. filgrastim) 
• Consider splenectomy if persistent symptomatic neutropenia
  

Manage infections promptly

• Prophylactic antibiotics not routinely recommended but early use during infection is critical
• Skin ulcer care

Complications and Prognosis

• Recurrent and severe infections
• Leg ulcers — difficult to treat, chronic
• Hematological malignancy (especially LGL leukemia)
• Bone marrow failure
• Ongoing neutropenia despite splenectomy

Prognosis depends on recurrent infection. Splenectomy may normalise Neutrophil count in 50-80 of refractory cases.

References

1. Owlia MB, Newman K. Felty’s syndrome, insights and updates. Open Rheumatol J. 2011;5:129–36.
   
2. Moosig F, et al. Large granular lymphocyte expansion in Felty’s syndrome and rheumatoid arthritis: a clinical and pathophysiological study. Arthritis Res Ther. 2008;10(3):R71.
   
3. Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233–55.