Edit concept Question Editor Create issue ticket

Felty's Syndrome

Felty syndrome

Felty syndrome (FS) is a potentially serious condition characterized by a triad of rheumatoid arthritis, splenomegaly, and granulocytopenia.


Presentation

History

The disease has a slow, insidious and destructive progress. Remission and exacerbations are the rule. Patients commonly report with a long-standing history of severe RA. Infrequently, RA and FS might develop together.

Plain radiography will confirm the presence of a long history of active, severe erosive joint disease in patients with FS. Sometimes, patients might present in a phase of remission with no active symptoms of joint disease but extra-articular manifestations like skin or respiratory infection might be seen.

Rarely, a patient might present with acute, left upper abdominal pain occasioned by a splenic infarct or splenomegaly. Weight loss, loss of appetite, mild fever and fatigue are often experienced by patients. With time, patients learn to recognize an oncoming exacerbation from minor signs.

Signs and symptoms

Involvement of bilateral, symmetrical, peripheral joints like knees, ankles, wrists, metacarpophalangeal (MCP) and proximal interpahalangeal joints (PIP) is common. Axial joint involvement is uncommon. Joint disease is accompanied with pain, swelling, redness and tenderness. Joint deformities typical of long-standing RA, for example, boutonniere deformity, z-shaped deformity, etc might be present.

Extra-articular manifestations

Lymphadenopathy, anemia and splenomegaly or hepato-splenomegaly distinguish FS from RA [4]. Splenomegaly is the reason behind pancytopenia. Pleuritis, pulmonary fibrosis, episcleritis and Sjogren syndrome are often seen accompanying a severe neutropenia.

Rheumatoid nodules might be present on the skin along with signs of vasculitis like shin ulcers, periungual infarcts, mononeuritis multiplex and brownish hyperpigmentation on lower legs.

Complications

Occasionally, a patient might present with a complication of FS like a splenic rupture post-dating a spleen infarct or a life-threatening respiratory or skin infection. Hematemesis or vomiting of blood due to portal hypertension is another potentially fatal complication of FS.

Splenomegaly
  • […] arthritis, splenomegaly and neutropenia Splenomegaly-neutropenia-rheumatoid arthritis syndrome edit English Felty's syndrome syndrome that results in rheumatoid arthritis, splenomegaly and neutropenia Felty syndrome Rheumatoid arthritis with splenoadenomegaly[wikidata.org]
  • […] of RA characterized by neutropenia and splenomegaly.[ncbi.nlm.nih.gov]
  • Splenomegaly is a condition of the spleen causing it to be enlarged. The splenic condition involving Felty syndrome is more specifically noted as inflammatory splenomegaly.[en.wikipedia.org]
  • Felty's syndrome is a triad of rheumatoid arthritis, neutropenia, and splenomegaly.[ncbi.nlm.nih.gov]
  • It is the triad of RA, neutropenia and splenomegaly.[patient.info]
Massive Splenomegaly
  • Splenectomy may be considered in those with massive splenomegaly or recurrent infections.[rheumaknowledgy.com]
  • Ideally liver biopsy should be done but a diagnosis of nodular regenerative hyperplasia was assumed, as our patient had a clinical picture of rheumatoid arthritis with massive splenomegaly, pancytopenia, portal hypertension and with other potential causes[autoimmunediseases.imedpub.com]
  • A spleen weight of 400-500 g indicates splenomegaly, while a weight of more than 1000 g is labelled massive splenomegaly.[emedicine.medscape.com]
Anemia
  • An acronym can be used to make recognizing this disease somewhat easier: S: Splenomegaly A: Anemia N: Neutropenia T: Thrombocytopenia A: Arthritis (rheumatoid) A complete blood count (CBC) can be done to diagnose anemia (normochromic, normocytic), thrombocytopenia[en.wikipedia.org]
  • Felty, American physician, 1895-1963 a group of pathological changes that occurs with adult rheumatoid arthritis, characterized by splenomegaly, leukopenia, frequent infections, and sometimes thrombocytopenia and anemia.[medical-dictionary.thefreedictionary.com]
  • Extra-articular manifestations Lymphadenopathy, anemia and splenomegaly or hepato-splenomegaly distinguish FS from RA. Splenomegaly is the reason behind pancytopenia.[symptoma.com]
  • Another Felty syndrome mnemonic I’ve seen used (see below) includes anemia and thrombocytopenia.[firstaidteam.com]
  • Abstract The syndrome of atrophic polyarthritis occurring in an adult, associated with fever, secondary anemia, leukopenia and splenomegaly, was described by Felty 1 in 1924.[annals.org]
Fatigue
  • Symptoms include: General feeling of discomfort ( malaise ) Fatigue Loss of appetite Unintentional weight loss Pale-looking skin Joint swelling, stiffness, pain, and deformity Recurrent infections Eye burning or discharge A physical exam will show: Swollen[nlm.nih.gov]
  • Other people may display a number of symptoms, including: fatigue serious infections a fever weight loss discolored patches of skin Sometimes, people who have Felty’s syndrome may not have any symptoms.[healthline.com]
  • Effects of Person-Centered Physical Therapy on Fatigue-Related Variables in Persons With Rheumatoid Arthritis: A Randomized Controlled Trial. Archives of Physical Medicine and Rehabilitation. 2016;97(1):26-36.[physio-pedia.com]
  • Anemia Eye burning or discharge Symptoms of Felty syndrome mnemonic Fatigue Anorexia Weight loss Recurrent infections due to neutropenia (lung and skin infections are most common). L eft upper quadrant pain (due to splenomegaly or splenic infarcts).[medical-institution.com]
Weight Loss
  • Symptoms include: General feeling of discomfort ( malaise ) Fatigue Loss of appetite Unintentional weight loss Pale-looking skin Joint swelling, stiffness, pain, and deformity Recurrent infections Eye burning or discharge A physical exam will show: Swollen[nlm.nih.gov]
  • Other people may display a number of symptoms, including: fatigue serious infections a fever weight loss discolored patches of skin Sometimes, people who have Felty’s syndrome may not have any symptoms.[healthline.com]
  • loss, strange skin rashes and mouth ulcers to name but a few.[feltyssyndrome.com]
  • Anemia Eye burning or discharge Symptoms of Felty syndrome mnemonic Fatigue Anorexia Weight loss Recurrent infections due to neutropenia (lung and skin infections are most common). L eft upper quadrant pain (due to splenomegaly or splenic infarcts).[medical-institution.com]
Saddle Nose
  • Necrotizing sinusitis and saddle nose deformity were distinctive clinical features.[ncbi.nlm.nih.gov]
Loss of Appetite
  • Symptoms include: General feeling of discomfort ( malaise ) Fatigue Loss of appetite Unintentional weight loss Pale-looking skin Joint swelling, stiffness, pain, and deformity Recurrent infections Eye burning or discharge A physical exam will show: Swollen[nlm.nih.gov]
  • Other symptoms of Felty syndrome include: Fatigue Loss of appetite Weight loss Pale skin Eye burning or discharge Treating Felty Syndrome “Treatment of Felty syndrome is treating the underlying disease [the rheumatoid arthritis] better,” says Goeckeritz[everydayhealth.com]
  • Signs and Symptoms of felty Syndrome • Swelling in joints • Loss of appetite • Fatigue • Burning in eyes • Pale skin • Stiffness • Some patients with FS may have ulcers on the lower legs, and discoloration or abnormal brown pigmentation of the skin, particularly[drthindhomeopathy.com]
  • Other times, they may have specific symptoms that occur with the syndrome, such as: eye discharge a burning feeling in the eyes fatigue weight loss joint pain, swelling, stiffness, and deformities a loss of appetite general discomfort infections pale[healthline.com]
Arthralgia
  • Side effects included rare cases of thrombocytopenia, arthralgias, and development of cutaneous leukocytoclastic vasculitis. Side effects were dose dependent and resolved when treatment was discontinued.[ncbi.nlm.nih.gov]
  • Case report A 17-year-old female with a 2-year history of erosive nodular seropositive RA followed Chinese herbal treatment for symptoms of repeated arthralgia in 2011.[spandidos-publications.com]
Headache
  • She also complains of a mild intermittent headache. Patient has chronic polyarticular pain, mostly on her left knee and ankles.[omicsonline.org]
  • He denied chest pain, shortness of breath, palpitations, cough, headache, dizziness, nausea, vomiting, abdominal pain, bowel or urinary symptoms, weight or appetite changes.[casesjournal.biomedcentral.com]
Intracranial Hemorrhage
  • The patient deceased of intracranial hemorrhage. It is likely, yet not definite, that high anti-citrullinated fibrinogen titers may contribute to low fibrinogen levels and could have contributed to the fatal hemorrhagic event.[ncbi.nlm.nih.gov]

Workup

A thorough physical examination is mandatory to locate any unreported signs by the patient.

Laboratory studies

A complete blood count will reveal anemia, severe neutropenia and thrombocytopenia with leucopenia. Serum titers of RF, anti-nuclear antibodies (ANA) and anti-histone antibodies (AHA) are high.

Mild elevations are noted in alkaline phosphatase, erythrocyte sedimentation rate (ESR) and serum transaminases due to portal hypertension and nodular hyperplasia of liver. In about 77% of cases, perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are also seen.

The significance of presence of ANA and p-ANCA in patients with FS is still not clear and it is doubtful they contribute to the disease itself either.

Histology

Samples might be obtained from the bone marrow and lymph nodes for histological studies. They will help rule out leukemia and large granular lymphocytosis (LGL). The bone marrow samples reveal normal megakaryocyte counts and myeloid hyperplasia. There is arrested growth of the immature cell lines in patients with FS.

Liver biopsy samples often reveal a nodular regenerative hyperplasia in FS. This is a result of portal hypertension due to splenomegaly. The condition is associated with portal fibrosis and might be complicated by an occluded portal venule due to a regenerative nodule.

Imaging

CT scan, ultrasound and radionuclide studies help to confirm the presence of splenomegaly and define its extent. They aid in assessing response to therapy in patients. Hepatomegaly might be noted on abdominal scans. Pulmonary fibrosis and pleurisy might be visible in chest CT scans and radiography.

HLA-DR3
  • A statistically significant association between the TNFA-308A allele and HLA-DR3, DQB1*0201, DQA1*0501, A1, B8, and the NcoI 5.5-kb RFLP of the TNFB gene was observed.[ncbi.nlm.nih.gov]
Hypercellular Bone Marrow
  • Autopsy showed extensive bronchopneumonia, fibrous pleuritis, congestive splenomegaly, mild atherosclerosis, reactive lymphoid hyperplasia, congested passive liver, severe rheumatoid arthritis, and hypercellular bone marrow.[ncbi.nlm.nih.gov]

Treatment

Controlling the underlying RA is the first and best way of treating FS. Close involvement of a rheumatologist, hematologist and infectious disease specialist are important for successful outcome.

Complete cure isn’t possible yet, thus remission for longer durations is sought after. Remission and palliation of presenting symptoms are the aims of treatment.

There was a time when gold salts were the only treatment available for RA and FS. Now, immunosuppressive agents like methotrexate and cyclophosphamide are the mainstay of palliative therapy. Both are anti-neoplastic agents.

While methotrexate helps reduce inflammation and its signs, cyclophosphamide reduces B and T cell counts thereby increasing infection risk. The exact method of action of methotrexate in reducing inflammation is not known yet in low doses, it acts an anti-inflammatory agent, extensively in RA. It is used as the first line of treatment in RA and even FS along with folic acid to prevent adverse effects. The good effects might take 4-8 weeks to become visible.

Hematopoeitic growth factors or Granulocyte-Colony Stimulating Factors (G-CSF) like filigrastim and sargramostim are used to stimulate neutrophil production, maturation and activation. They increase the migration and cytotoxicity of mature neutrophils, helping antibiotics act better. Sargramostim especially stimulates cell division and maturation of early cell lines of myeloid and macrophage precursors.

A new class of medications called monoclonal antibodies has emerged in the recent years as an outfall of genetic engineering. These are chimeric murine or human immunoglobulins that are directed against the proteins that are involved in initiation of cell cycles.

Rituximab, a genetically manufactured human monoclonal antibody, is used as second line treatment in refractory cases of FS. It acts against the CD20 antigens of the normal and malignant B cells [5] [6]. Etanercept, infliximab and adalimumab are used to treat RA extensively for their anti-TNF-alpha (Tumor Necrosis Factor) properties but their use in FS is limited.

Splenectomy might be opted for in severe cases of neutropenia with no response to medical therapies. Occasionally, recurrent cutaneous ulceration and extrinsic hemolysis might need a splenectomy. Splenectomy hasn’t shown to correct neutropenia in all the cases and high rates of recurrence have been noted in patients. 80% patients noticed improvement in neutropenia post-splenectomy [7].

Prognosis

The prognosis for FS is poor given the low neutrophil counts causing repeated life-threatening infections. Skin and pulmonary infections are most common.

Extensive use of immunosuppressants for treating RA and FS further worsens the morbidity and mortality. A study from England observed that 5 out of 32 patients of FS died due to fulminant bronchopneumonia [8].

Etiology

The exact cause of FS is not known but several risk factors have been implicated:

  1. Long-standing rheumatoid arthritis (RA)
  2. High titers of Rheumatoid Factor (RF positivity)
  3. Extra-articular manifestations
  4. Aggressive synovitis
  5. Human Leucocyte antigen (HLA) – DR4 positivity

Epidemiology

FS affects about 1-3% of RA patients after having arthritis for an average of 10-15 years. RA itself affects 1% of the population, making FS a rare diagnosis.

Men are affected in later years as compared to women. FS is rare in the African American population and in children. It is 3 times more prevalent in females, especially in their fifties [2] [3].

No significant international data is available about its prevalence in other countries. Also, since patients may be asymptomatic, even the data available might be an underreporting.

Sex distribution
Age distribution

Pathophysiology

The exact pathophysiology of FS is unclear but underlying autoimmune mechanisms against neutrophil surface antigens are thought to be responsible.

A high incidence of infections might initiate a neutrophil response leading to histone deimination and chromatin expulsion from the cell.

Bacterial adjuvants and deiminated histones together with Neutrophil Extracellular chromatin Traps (NETs) are the most possible trigger for antibody production against these deiminated histones. These auto-antibodies further stimulate the neutrophils leading to a self-sustaining cycle causing repetitive depletion of neutrophils.

Studies have demonstrated high incidences of auto-antibodies against deiminated histones in FS patients.

Prevention

There are no guidelines for prevention of Felty’s Syndrome

Summary

Felty’s syndrome (FS) was first identified in 1924 and named after its discoverer Augustus Roi Felty [1]. It is a triad of rheumatoid arthritis (RA), splenomegaly and neutropenia

Felty’s syndrome can lead to potentially fatal complications due to high chances of recurrent bacterial infections. It has been nicknamed ‘super rheumatoid’ by some, owing to the extreme joint affections seen in patients.

Patient Information

Felty’s Syndrome is a triad of enlarged spleen, low neutrophil counts and rheumatoid arthritis. It is most commonly seen in middle aged adults, especially in females in their fifth decade of life. It is commonly seen in people with rheumatoid arthritis of long standing.

The exact cause for it is unknown but auto-immune mechanisms have been found to play a strong role in initiating and worsening the condition.

The symptoms of rheumatoid arthritis are seen- joint pains, swelling, deformities of small joints of both hands and feet. Symptoms related to low neutrophil counts are recurrent fevers and infections and ulcers on legs. Vasculitis and splenomegaly related symptoms like skin hyperpigmentation, lymph node enlargements, spleen infarcts, portal hypertension, anemia, neutropenia and low platelet counts might be visible too.

Diagnosis is made with a series of blood tests to look for antibodies. Imaging studies may be done to look for organ enlargements and bone disorders.

Treatment involves medications that suppress the immune system and control inflammation due to it. Steroids and other molecules like methotrexate, haemotopoeitic growth factors are the chief drugs used for controlling Felty Syndrome.

Educating patients about the gravity of the condition, chances of recurrent infections and ensuring access to healthcare are the chief goals. A list of antibiotics for specific infections might be given to patients with instructions of contacting their physician at the first signs of an infection and starting the antibiotics after due confirmation. Patients should be taught how to prevent infections by adequate personal and home hygiene.

References

Article

  1. Felty AR. Chronic arthritis in the adult, associated with splenomegaly and leucopenia. A report of 5 cases of an unusual clinical syndrome. Bulletin of the Johns Hopkins Hospital, Baltimore, 1924, 35: 16.
  2. Goldberg J, Pinals RS. Felty syndrome. Semin Arthritis Rheum 1980; 10:52.
  3. Sibley JT, Haga M, Visram DA, Mitchell DM. The clinical course of Felty's syndrome compared to matched controls. J Rheumatol 1991; 18:1163
  4. Al-Ghamdi A, Attar SM. Extra articular manifestations of rheumatoid arthritis: a hospital based study. Ann Saudi Med. 2009 May-Jun; 29(3):189-93.
  5. Tomi AL, Liote F, et al. One case of Felty’s Syndrome efficiently treated with rituximab. Joint Bone Spine. 2012 Dec;79(6):624-5.
  6. Narvaez J, Domingo Domenech E, et al. Biological agents in the management of Felty’s Syndrome: a systematic review. Semin Arthritis Rheum. 2012 Apr;41(5):658-68.
  7. Balint GP, Balint PV. Felty’s Syndrome. Best Pract Res Clin Rheumatol. 2004 Oct;18(5):631-45.
  8. Campion G, Maddison PJ, Goulding N, James I, Ahern MJ, Watt I, et al. The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations. Medicine (Baltimore). Mar 1990;69(2):69-80.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 21:52