Felty Syndrome Treatment & Management

The best way of treating Felty syndrome (FS) is to control the underlying rheumatoid arthritis (RA). Immunosuppressive therapy for RA often improves granulocytopenia and splenomegaly; this finding reflects the immune-mediated nature of FS. Most of the traditional medications used to treat RA have been used in the treatment of FS. No well-conducted, randomized, controlled trials support the use of any single agent. Most reports on treatment regimens involve small numbers of patients.

Surgical treatment (ie, splenectomy) may be warranted in certain cases.

Hospital admission is mandatory for patients with serious life-threatening infections; cultures and parenteral antibiotics are indicated in such situations. It is important to acknowledge the possibility of infection with encapsulated organisms because splenomegaly may be a marker for a dysfunctional reticuloendothelial system incapable of clearing these organisms. Staphylococcus aureus, streptococcal species, and gram-negative rods are potential infecting organisms.

Consult the following specialists as needed:

• Rheumatologist
• Hematologist
• Infectious diseases specialist

Methotrexate is the agent preferred by rheumatologists for treating RA. Currently, almost all patients with RA are treated with methotrexate. If urgent correction of neutropenia is unnecessary, most practicing rheumatologists use methotrexate first when treating FS, usually in combination with folic acid to minimize adverse effects. Methotrexate is typically administered orally in low doses for FS. ^[1] The beneficial effects of methotrexate may not be evident until 4-8 weeks after the initiation of therapy.

Because of the potential for leukopenia, cyclophosphamide is of limited utility in this setting, although it may have a role in some cases. A small number of patients with refractory FS have been reported to respond to high-dose cyclophosphamide ^[10] ; however, physicians have had far more experience using cyclophosphamide for rheumatoid vasculitis and other serious RA extra-articular manifestations than for FS. For this reason, this agent is not a preferred initial choice for treatment of FS.

Recombinant granulopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), effectively and quickly raise the granulocyte count, which is important in patients with life-threatening infections. Initial treatment of patients with FS and life-threatening infections should include administration of a growth factor. Long-term use of G-CSF appears to be well tolerated, though hypersensitivity vasculitis and flareups of the underlying RA have been reported.

The tumor necrosis factor alpha (TNF-α) inhibitors etanercept, adalimumab, and infliximab are disease-modifying antirheumatic drugs (DMARDs) that have proved very effective in the treatment and control of RA. Clinical experience with them in FS is comparatively limited, but consensus has built that they do not offer much benefit in FS. ^[11]

Initial reports on using rituximab to treat FS were negative, ^[12] but subsequent reports were more encouraging. ^{[13, 14, 15]} Current data suggest that rituximab should be considered in refractory FS. ^[16]  Rituximab is becoming a preferred biologic treatment choice, with a better response pattern than anti-TNF agents. ^[17]  

Case reports describe successful treatment of FS with other DMARDs approved for use in RA. One report describes relief of clinical symptoms and resolution of splenomegaly with the interleukin-6 receptor antagonist tocilizumab. ^[18] In another patient with FS, whose neutropenia had not responded to G-CSF, the absolute neutrophil count normalized after initiation of abatacept, a chimeric protein that inhibits T-lymphocyte activation. ^[19]

At high doses, corticosteroids can increase the granulocyte count, partly through demargination. This effect does not persist when the dose is tapered to a typical low dose (< 10 mg/day) used for RA articular disease. Empiric administration of high-dose IV methylprednisolone is often prescribed for FS, but the effect is time-limited. Long-term use of high-dose corticosteroids further increases the risk of infection. Corticosteroids should probably be viewed as a second-line treatment modality.

Case reports from the 2000s noted a lack of response to leflunomide ^[20] and a response to salazosulfapyridine. ^[21]  Penicillamine is used infrequently in RA because of its adverse effect profile, and it is never a first-choice therapy for patients with FS. Intravenous immunoglobulin (IVIg) has not been demonstrably successful on a reproducible basis.

At one time, most FS patients were treated with gold salts, on the basis of these agents’ long history of use in RA before the advent of methotrexate; however, FS responds only slowly to gold salts. Older studies report a response rate of 60-80%. Intramuscular aurothioglucose was once the most commonly used agent for FS but is now of only historic note.

Splenectomy is recommended only in patients with severe intractable disease who exhibit no improvement with medical therapy and who are experiencing recurrent or serious infection. Less commonly, extrinsic hemolysis or recurrent cutaneous ulcers may indicate a need for splenectomy. Granulocytopenia recurs in approximately 25% of patients who have undergone splenectomy.

Patients with FS should be scheduled for regular follow-up with a rheumatologist to monitor therapy and to assess progress.

No firm guidelines address immunization practice in FS patients, but ensuring vaccination against encapsulated organisms seems prudent.

Recommended patient activity levels should be dictated by infection risk and spleen size. In general, patients should avoid any activity that could result in blunt trauma to the left upper quadrant.