Felty’s SyndromeFelty’s SyndromeSham A. Cader, Eugeniusz J.

KucharzDepartment Of Internal Medicine and

RheumatologyMedical 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 life-threatening 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 (G-CSF).

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 non-palpable (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

• 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• 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.