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A. Definition

  1. Rheumatoid factor positive (RF+) rheumatoid arthritis (RA)
  2. Neutropenia, <2,000 neutrophils/µL
  3. Splenomegaly

B. Characteristics

  1. Age 40-60
  2. Female ~65%; Non-Black ~95%
  3. HLA-DRw4 ~95%
  4. Weight Loss 65%
  5. Rheumatoid Nodules ~75%
  6. Sjogren's Syndrome ~55%
  7. Lymphadenopathy ~35%
  8. Infections Common [1]
    1. Usually correlates with level of neutropenia (particularly <500/µL)
    2. Elevated endogenous levels of granulocyte colony stimulating factor (G-CSF) predicts risk for infection
    3. Levels of soluble Fc-gamma receptor III were lower in patients with infections
  9. p-ANCA found in a majority of the patients [2]

C. Pathophysiology

  1. Not well understood
  2. Variant of generally severe RA usually with rheumatoid nodules
  3. Neutropenia [3]
    1. Autoantibodies against G-CSF; neutralizing in some patients
    2. Hyposensitivity of neutrophils to G-CSF found in other patients
    3. Hyposensitivity to G-CSF leads to lack fo feedback inhibition and elevation of G-CSF levels
  4. Generalized immune dysfunction
    1. Splenomegaly
    2. Lymphadenopathy
    3. Rheumatoid nodules

D. Non-Hodgkin's Lymphoma (NHL) Risk [4,5]

  1. Marked (>30X) increased risk for NHL development
  2. Clonality has been demonstrated in large granular lymphocytes in some patients
    1. Other patients have large granular lymphocyte lymphomas often with arthritis
    2. Increased incidence of large granular lymphocyte leukemia as well
    3. These tumors are usually clonal T cell neoplasms, CD3+, CD57+
    4. Other cancers also have mildly increased incidence

E. Treatment

  1. Prednisone short course for induction; treats the arthritis and neutropenia
  2. Methotrexate (MTX) [6,7]
    1. Low dose (7.5-10mg q week) MTX should be initiated with prednisone
    2. Recommended for all Felty's syndrome as disease modifying agent
    3. Improves both arthritis and neutropenia
  3. Cyclosphosphamide (Cytoxan®) [8]
    1. Immunoablative doses of cyclosphosphamide can be used
    2. Efficacy in two patients with severe Felty Syndrome demonstrated clearly
    3. Requires growth factor (G-CSF) and blood product support
    4. Does not require stem cell reinfusion/rescue (avoids autoaggressive lymphocytes)
    5. Alopecia is the major side effect
    6. Neutropenia generally not a major problem with G-CSF and antibiotics
    7. Gonadal failure is very uncommon
  4. Colony Stimulating Factors (CSF's)
    1. Effective in resistant Felty's
    2. G-CSF [9,10] or GM-CSF [11] improves neutropenia in Felty's Syndrome
    3. CSF side effects include increased arthritis [12,13], low platelets [11], vasculitis [13]

Resources

calcAbsolute Neutrophil Count

References

  1. Hellmich B, Csernok E, de Haas M, et al. 2002. Am J Med. 113(2):134 abstract
  2. Kallenberg CGM and Tervaert HWC. 1992. Am J Med. 93(12):675
  3. Hellmich B, Csernok E, Schatz H, et al. 2002. Arthritis Rheum. 46(9):2384 abstract
  4. Gridley G, Klippel JH, Hoover RN, Fraumeni JF Jr. 1994. Ann Intern Med. 120(1):35 abstract
  5. Bowman SJ, et al. 1994. Arthritis Rheum. 37(9):1326 abstract
  6. Hamidou MA, Sadr FB, Lamy T, et al. 2000. Am J Med. 108(9):730 abstract
  7. Wassenberg S, Herborn G, Rau R. 1998. Brit J Rheumatol. 37(8):908 abstract
  8. Brodsky RA, Petri M, Smith BD, et al. 1998. Ann Intern Med. 129(12):1031 abstract
  9. Yasuda M, et al. 1994. Arthritis Rheum. 37(1):145 abstract
  10. Wun T. 1993. Ann Intern Med. 118:318 abstract
  11. Moore DF Jr and Vadhan-Raj S. 1995. Am J Med. 98(6):591 abstract
  12. DeVries EGE, Willemse PHB, Biesma B, et al. 1991. Lancet. 338:517 abstract
  13. Vidarsson B, Geirsson AJ, Onundarson PT. 1995. Am J Med. 98(5):589