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Felty’s Syndrome
Sham A. Cader, Eugeniusz J. Kucharz
Department Of Internal Medicine and Rheumatology
Medical University Of Silesia
Katowice - Poland
Felty’s syndrome represents one of many
systemic complications of seropositive
rheumatoid arthritis.
• In 1924 by A.R Felty described the triad of
chronic arthritis, splenomegali and
ganulocytopenia
Prevalence
• The true prevalence of Felty’s syndrome
is unknown, but it may be as high as 3
percent in seropositive rheumatoid
arthritis patients.
• In the US Felty’s syndrome affects
approximately 1-3% of all patients
diagnosed with RA and RA occurs in
about 1% of the general population.
Mortality and Morbidity
• Although many patients are asymptomatic
but others progress and develop lifethreatening infections.
• Pulmonary and skin infections are common.
• One study from the southwest of England
observed 32 patients with Felty’s syndrome; 5
died from bronchopneumonia during a mean
follow-up period of 5.2 years.
( Bath Institute for Rheumatic Diseases, UK)
Race
•
Felty’s syndrome most often occurs in whites and
infrequently occurs in blacks.
• The human leukocyte antigen DR4
(HLA-DR4) genotype, which is a marker for more
aggressive RA and more frequent extraarticular
manifestations in whites, is strongly associated
with Felty’s syndrome.
• Also appear to be a DQ-linked susceptibility gene
and a C4B-null allele that increase the risk of
Felty’s syndrome.
• Incidence in women exceeds incidence in men by
a ratio of 3:1.
Pathogenesis
• Mechanism for the development of
granulocytopenia include accelerated
removal of granulocytes from the circulating
pool and suppression of granulopoiesis.
• Adherence of specific antibodies directed
against granulocyte cell surface antigens,
ingestion and surface-coating of immune
complexes leads to impaired granucyte
function and facilitates their removal by the
reticularendothelial system.
• Sequestration and margination of
granulocytes in the spleen and venules in the
lungs and elsewhere results in a diminished
circulating pool.
• Impaired production is caused by humoral or
T cell suppression of myelopoiesis or
inhibition of granulocyte growth factor
production by cytokines.
• A study performed in „Medizinische Universitat zu Lubeck”
Germany, patients with Felty’s syndrome have auto
antibodies against granulocyte colony-stimulating factor (GCSF).
Clinical Features
• Classic triad
Chronic arthritis
Active rheumatoid arthritis is present in
about 60% patients. ranges from mild
involvement to severe deformity and
erosion of the joints.
Splenomegaly
Firm non tender spleen, ranges from nonpalpable (5-10% of cases) to massive.
There is no correlation between spleen
size and the degree of leukopenia also
mild hepatomegaly is common.
Rare complications: splenic rupture, potal hypertension with
esophageal verices.
Leukopenia
• Recurrent serious infections in about
60% of patients; most common are skin
infections (abscesses, cellulitis, furunculosis)
• The degree of leukopenia does not correlate
well with number and severity of infections
• Granulocytopenia may develop in just weeks
and spontaneous remmisions are uncommon
Extra-Articular Manifestations
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Rheumatoid nodules (76%)
Weight loss (68%)
Sjögren’s Syndrome (56%)
Lymphoadenopathy (34%)
Leg ulcers (25%)
Pleuritis (19%)
Skin pigmentation (17%) – pulpable pupura and
brownish pigmentary changes of the lower
extremities.
• Peripheral neuropathy (17%)
• Episcleritis (8%)
Hematologic and Serologic
features
CBC
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Granulocutopenia
neutrophils usually between 1000- 2500/µL but can be
<500/µL
Lymphopenia in 33%
Eosinophilia may be present in some
Usually a lack of left shift and immature cells with a normal
number of bands
Anemia – mild-moderate normocytic normochromic anemia
with an elevated reticulocyte count
Thrombocytopenia – in 38% but seldom causes purpura
Composite of lymphocytes: 1 large granular lymphocyte (LGL) in top
left frame, 1 large lymphocyte in center frame, 3 medium
lymphocytes in lower left and right frames. Normal blood - 100X
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%
Bone Marrow
• Myeloid hyperplasia with a relative
excess of immature forms (maturational
arrest)
• Depressed myeloid activity or increased
lymphocyte infiltration
• This low-oil magnification view is of a bone marrow aspirate
in a patient with Felty's syndrome. Maturation arrest is at the
metamyelocyte stage. There is significant reactive
plasmocytosis (30%). A "Mott Cell" with grape-like inclusions
is seen in the top center of the field
Liver Biopsy- Nodular Regenerative
Hyperplasia
The pale tan discrete nodules of nodular regenerative
hyperplasia have been mistaken for cirrhosis or even
metastatic carcinoma.
Nodular sinusoidal lymphocytes in
Felty’s syndrome
• Image donated by: Professor Ian Lauder
Donor organization: Leicester University, Department of Pathology
Management
• The best treatment for Felty’s syndrome is to
control underlying rheumatoid arthritis.
Immunosuppresive therapy ( high doses of corticosteroids,
Methotrexate, gold salts )
• The potential for leukopenia limits the use of
cyclophosphamids
• Penicillamine is bieng used less frequenty for RA because of
its side effect profile.
• Etanercept and infliximab are 2 newer agents prescribed for
RA. These agents effects of tumor necrosis factor-alfa
(TNF-  ).These drugs are very effective in the treatement and
control of RA
• Intravenous immunoglobulin does not show
reproducibly success.
• Recombinant granulopoietic growth factors , such
as granulocyte colony-stimulating factor (G-CSF)
and granulocyte-monocyte colony- stimulating
factor (GM-CSF, effectively and quickly raise the
granulocyte count, which is important for the
patients with life threatening infections
• Splenectomy is only recommended for patients
with severe ,intractable disease who exhibit no
improvement with medical therapy and suffering
fro recurrent or serious infection
• Though Felty’s syndrome appears to be rare
in rheumatoid arthritis patients, a proper
complete diagnosis should be done in all
RA patients and proper control of the RA.