What is Felty syndrome?

Felty's Syndrome: Definition and Management

Felty's syndrome is a rare condition characterized by the triad of rheumatoid arthritis (RA), neutropenia, and splenomegaly, which increases susceptibility to infections due to neutropenia and represents a complication of longstanding seropositive RA.

Clinical Features and Diagnosis

• Felty's syndrome is most commonly seen as a complication of longstanding rheumatoid arthritis, typically in patients who are seropositive (RF+, anti-CCP+) 1, 2
• The classic triad consists of:
  • Rheumatoid arthritis (typically longstanding)
  • Neutropenia (absolute neutrophil count <2000/μL)
  • Splenomegaly (which can range from mild to massive) 1, 3
• In rare cases, Felty's syndrome can present without clinical manifestations of arthritis but with laboratory evidence of RA (positive rheumatoid factor and anti-CCP antibodies) - termed "non-articular Felty's syndrome" 4, 5
• The syndrome has a strong association with HLA-DR4, DQ beta 3b, and C4B null allele, suggesting genetic predisposition 2

Differential Diagnosis

• Differential diagnosis is broad and includes:
  • Hematologic malignancies (particularly lymphoma)
  • Other autoimmune disorders
  • Large granular lymphocyte syndrome (pseudo-Felty's syndrome)
  • Infections causing splenomegaly
  • Other causes of neutropenia 3, 1
• Pseudo-Felty's syndrome (proliferation of large granular lymphocytes with neutropenia) can be confused with traditional Felty's syndrome but has distinct clinical and laboratory features 2

Complications

• The major sources of morbidity and mortality in Felty's syndrome are recurrent local and systemic infections due to neutropenia 2
• Skin manifestations are common, including leg ulcers that can be difficult to heal 1
• The hemophagocytic lymphohistiocytic syndrome can be associated with Felty's syndrome 3

Management Approach

• Treatment should target both the underlying rheumatoid arthritis and the neutropenia 6
• First-line therapy typically includes:
  • Systemic corticosteroids (prednisone) to rapidly improve neutropenia 1, 4
  • Methotrexate as a disease-modifying antirheumatic drug (DMARD) to control the underlying RA 1
• For severe neutropenia with recurrent infections:
  • Granulocyte colony-stimulating factor (G-CSF/filgrastim) can effectively increase neutrophil counts and reduce infection risk 1, 7
  • Monitor for potential side effects of G-CSF including mild thrombocytopenia and possible flares of arthritis 7
• In fulminant disease refractory to medical management:
  • Splenectomy may be considered for patients with severe, refractory neutropenia 2
  • Lithium carbonate has been used in some cases 2
• For patients with peristomal pyoderma gangrenosum (a potential complication), closure of the stoma might lead to resolution of the lesions 3

Monitoring and Prognosis

• Regular monitoring of complete blood counts is essential to assess neutropenia 1
• Early recognition and treatment can significantly improve outcomes 1
• The condition may have a high recurrence rate, requiring long-term management 6
• With appropriate treatment, clinical improvement can include reduction in joint symptoms, spleen size, and healing of skin ulcers 1

Special Considerations

• Felty's syndrome should be considered in the differential diagnosis when encountering unexplained splenomegaly and neutropenia, even without a history of chronic RA 1
• The condition can be confused with other hematologic disorders, so thorough diagnostic workup is crucial 1, 2
• In some cases, Felty's syndrome may precede the clinical manifestations of RA, making diagnosis challenging 4, 5