FELTY'S SYNDROME
DEFINITION:
A rheumatoid disorder characterized by the classic triad of
neutropenia, splenomegaly, and rheumatoid arthritis.
EPIDEMIOLOGY:
- incidence: less than 1% of patients with rheumatoid arthritis
- age of onset:
- peaks in the 4th-7th decades; range 18-70 years
- risk factors:
- rheumatoid arthritis
- F > M (2:1)
- HLA DRw4 in 95% of patients
- rare in blacks
PATHOGENESIS:
- first described by A. R. Felty in 1924 in 5 patients with
common findings: chronic arthritis, splenomegaly, leukopenia,
marked weight loss with undernourishment, yellowish-brown
pigmentation of the skin, middle age (John Hopkins Hospital
Bulletin No. 395: p.16-20 [1924])
- thought of as a distinct clinical entity superimposed upon
an established rheumatoid arthritis which has been symptomatic
for over 3 years, i.e., a severe variant of seropositive
rheumatoid arthritis
- on average, Felty's Syndrome develops 15 years after the
onset of rheumatoid arthritis
2. Pathogenesis
- unknown etiology but probably a combination of increased
removal of and impaired production of granulocytes:
- adherence of antibodies to the cell surface of
granulocytes (IgG, immune complexes, complement, and/or
granulocyte-specific ANA) may increase the destruction of
granulocytes and/or increase margination and sequestration
of the granulocytes
2. Impaired Production
- specific T-cells may act as a suppressor of
granulocyte colony formation in the bone marrow
CLINICAL FEATURES:
- active rheumatoid disease is present in about 60%
- ranges from mild involvement to severe with deformity and
erosion of the joints
2. Splenomegaly
- firm, non-tender spleen
- ranges from non-palpable (5-10% of cases) to massive
- median weight is about 4x normal
- there is no correlation between spleen size and the degree
of leukopenia
- rare complications: splenic rupture, portal hypertension
with esophageal varices
- mild hepatomegaly is common
3. Leukopenia
- recurrent serious infections in about 60% of patients
- most common are skin infections (abscesses, cellulitis,
furunculosis) followed by respiratory tract infections and
urinary tract infections
- rarely get oral ulcers, sinusitis, otitis media,
osteomyelitis, and septic arthritis
- the degree of leukopenia does not correlate well with the
number and severity of infections
- most infections are caused by common bacteria, i.e., staph.,
strep., gram negative bacilli
- granulocytopenia may develop in just weeks and spontaneous
remissions are uncommon; the granulocytes may return to the
normal range during a infection (but are not elevated)
2. Extra-Articular Manifestations
- rheumatoid nodules (76%)
- weight loss (68%)
- Sjogren's Syndrome (56%)
- lymphadenopathy (34%)
- leg ulcers (25%)
- pleuritis (19%)
- skin pigmentation (17%)
- neuropathy (peripheral) -17%
- episcleritis (8%)
- others: pericarditis
- is usually between 10-15% of body weight
- may be striking and occur for several months before the
diagnosis is made
2. Skin Pigmentation
- yellowish brown pigmentation over the exposed surfaces
of the extremities, i.e., tibia
- may be related to stasis and extravasation of RBC's due
to small vessel disease
3. Leg Ulcerations
- mostly occur over the tibias and ankles
- indolent without a marked inflammatory reaction
- biopsy of ulcer may suggest a vasculitis
- may also be ulcerations of the mouth and corneas
INVESTIGATIONS:
- neutrophils usually between 1,000-2,500/uL but can be
<500/uL
- lymphopenia in 33%
- eosinophilia may be present in some
- usually a lack of left shift and immature cells with a
normal number of bands
2. Anemia
- mild-moderate normocytic normochromic anemia (of chronic
disease) with an elevated reticulocyte count
3. Thrombocytopenia
- in 38% but seldom causes purpura
2. Serum
- high Rf titre in 98%
- ANA in 67%
- elevated ESR, immunoglobulins, circulating immune complexes
- positive LE cell test in 33%
- decreased complement levels
- elevated transaminases and alkaline phosphatase in 25-50%
3. Bone Marrow
- variable findings
- normal in some
- myeloid hyperplasia with a relative excess of immature
forms (? maturational arrest)
- may also show depressed myeloid activity or increased
lymphocyte infiltration
4. Liver Biopsy
- perhaps due to recurrent embolization of the portal veins
by platelet aggregation
- may account for the mild abnormalities in liver function
tests
- not specific for Felty's Syndrome
- may also see portal expansion and fibrosis +/- portal
hypertension
MANAGEMENT:
- recurrent or serious infections
- severe ulcers
- severe and persistent granulocytopenia (<500 mm3)
- severe anemia due to hypersplenism
- thrombocytopenic haemorrhage due to hypersplenism
2. Results
- results in a prompt hematologic response within minutes to
hours of splenectomy (but may not persist)
- may also improve thrombocytopenia, anemia, and leg ulcers
- recurrence of granulocytopenia in 25% despite splenomegaly
- patients may show the same susceptibility to infection
before and after splenectomy
- may be a transient improvement in the synovitis
- the benefits must be weighed against the potenital
compli-cations (increased susceptibility to overwhelming
sepsis, postoperative complications)
2. Medical
- treat the underlying rheumatoid arthritis
- monitor for and treat infections with appropriate anti-biotics
- administer pneumococcal vaccine
2. Lithium Carbonate
- may enhance granulocyte colony-stimulating activity and
increase the granulocyte count
- response ranges from dramatic to cyclic to none
- appears to be safe and effective in selected patients
3. Immunosuppression
- use is controversial
- may improve granulocytopenia by decreasing the pool of
marginated cells
- may predispose to infection
- may be used if the patient is severly anemic due to
splenic destruction of RBC's
2. Others
- gold, penicillamine, azathioprine, cyclophosphamide
3. Prognosis
- the arthritis can range from a benign course with episodes
of remission to severe
- majority of patients, though, have severe deforming
arthritis
- infection is the major cause of death
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