Felty’s Syndrome
August 10, 2006 Morning Report
The Felty’s Triad
Long-standing RA
(usually severe)
Splenomegaly
Granulocytopenia
(ANC <2000/mm3)
Who gets FS?
FS: 1-3% of pts with RA RA: 1% of population F:M 3:1 Typically occurs in pts 50-70yo who have had RA for >10y
Risk Factors
RF positivity in high titers Long-standing disease (>10y) Aggressive and erosive synovitis HLA-DR4 positivity and DR4 homozygosity Extra-articular RA manifestations
Elements of a FS History
>10 years of RA with active or burnt-out joint disease Recurrent bacterial infections: skin and respiratory tract 2° to granulocytopenia RUQ pain 2° splenic infarct or capsular distention Fatigue, anorexia, weight loss, eye burning and/or discharge
Physical Findings in FS
Splenomegaly, mild hepatomegaly LAD Rheumatoid nodules Sjögren syndrome Articular findings of long-standing RA
Joint deformities Synovitis (joint swelling and tenderness), may be mild
Physical Findings in FS
Small-vessel inflammation (vasculitis)
Lower extremity ulcers and purpura Periungual infarcts
Signs of systemic vasculitis
Mononeuritis multiplex Extremity ischemia
Pleuritis, peripheral neuropathy, episcleritis, and signs of portal hypertension
Diagnosis
CBC w/ dif:
Persistent granulocytopenia (<2000/μl) Anemia, thrombocytopenia 2° to splenic sequestration Anemia of chronic dz may also be present
ALP and Transaminase (mild elevation) High titers of RF (98%) ANAs (67%), antihistone antibodies, p-ANCA (77%) Elevated ESR and serum immunoglobin levels Cryoglobulins may be present Bone marrow bx or blood smear to R/O Pseudo-Felty’s
FS: nl megakaryocytes, myeloid hyperplasia with immature cell forms
Etiology of Granulocytopenia
Cause unknown, but theories include:
Abnl WBC development 2° to decreased G-CSF Splenic sequestration of WBC Immune destruction of WBC 2° to autoantibody generation against granulocyte surface antigens
Treatment
Control underlying RA w/ immunosuppressive therapy
Gold salts (DMARD) Methotrextate (DMARD) (TOC) + folic acid Cyclophosphamide and penicillamine Etanercept and Infliximab
G-CSF and GM-CSF (when life-threatening infection) High-dose corticosteroids (2nd line treatment) Splenectomy
Severe intractable disease and recurrent or serious infection Extrinsic hemolysis or recurrent cutaneous ulcers (less common) Granulocytopenia can recur after splenectomy (25%)
Complications
Splenic rupture Life-threatening infection Toxicity from immunosuppressive regimens Increased risk of NHL
Pseudo-Felty’s Syndrome
Chronic leukemia w/ clonal expansion of large granular lymphocytes (LGL Syndrome) <1% of patients w/RA, usually at onset of RA Less severe RA with absent RF (30%) Neutropenia w/ nl/ ↑ WBC count Thrombocytopenia, anemia, splenomegaly, arthritis (30%) Therapy rarely necessary