Felty Syndrome in Long-standing Rheumatoid Arthritis
Published : Jan 01, 2023

Abstract 

Felty syndrome is a rare autoimmune disorder associated with long-standing rheumatoid arthritis. It affects 1-3% of the population affected by rheumatoid arthritis and is more prevalent in females. The presence of the HLA-D4 gene increases the risk of predisposition to the Felty Syndrome. The patient is affected by neutropenia as a result of an autoimmune response, and it gives rise to recurrent infections. The mixed picture can falsely represent other conditions such as systemic lupus erythematosus, chronic lymphocytic leukemia (CLL), and other hematological disorders, sarcoidosis, amyloidosis, lymphomas, or other malignancies, etc. Early diagnosis is crucial in managing the complex and peculiar disorder, as the condition is managed with multifactorial treatment based on the symptomatology.  In this case report, we have discussed the case of an adult male who presented with a non-healing leg ulcer. He was found to have hepatosplenomegaly on abdominal ultrasound, and vasculitis was detected by skin biopsy. The patient was treated for the underlying causes. 

Keywords

Felty syndrome, Rheumatoid arthritis, Neutropenia, Splenomegaly, Vasculitis, Immunosuppressive 

Introduction 

The American doctor Augustus Roi Felty first identified Felty’s syndrome (FS) in 1924. This syndrome remains challenging to diagnose and treat even after almost a century [1]. It is an uncommon phenomenon associated with Rheumatoid Arthritis. It is manifested with a triad that includes joint involvement, splenomegaly, and neutropenia. Although a patient does not necessarily represent all three conditions, consistent neutropenia (ANC < 1500 mm3) is a definitive indication of Felty Syndrome [1]. Autoantibodies, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are commonly present in rheumatoid arthritis, may contribute to the destruction of neutrophils [1].  

 

Neutropenia in Felty Syndrome is thought to be related to the underlying autoimmune process associated with rheumatoid arthritis (RA), which is a critical component of Felty Syndrome. The exact cause is not fully understood, but several mechanisms may contribute to the development of neutropenia in this context. The same autoimmune process that causes rheumatoid arthritis can affect the bone marrow, where neutrophils are produced. Chronic inflammation in rheumatoid arthritis may lead to bone marrow suppression, affecting the normal production of blood cells, including neutrophils. The inflammatory milieu can disrupt the balance of hematopoiesis in the bone marrow [2]. 

 

Splenomegaly leads to neutropenia by causing neutrophil sequestration and peripheral destruction. It has also been observed that the drop in circulating granulocyte colony-stimulating factor (G-CSF) causes an indirect decrease in neutrophils [2]. 

 

There may be genetic predispositions that influence the development of Felty Syndrome. The presence of the HLA-DR4 gene increases the risk of Felty syndrome. Splenomegaly and immunologic factors are two causes of multifactorial neutropenia in Felty syndrome. Environmental factors such as immunosuppressive drugs and additional genetic factors could contribute to the complex pathophysiology of both rheumatoid arthritis and Felty Syndrome [2]. The spleen produces immune complexes that impair the survival of neutrophils, while leukemic cytotoxic T-cells express Fas that causes a defect in marrow proliferation. These two pathways, involving antibodies and cells, trigger the death of granulocytes through different mechanisms inside the cells. These mechanisms can coexist and happen at the same time in some patients with T-cell large granular lymphocyte leukemia or Felty Syndrome [3].  

 

It’s important to note that the mechanisms underlying neutropenia in Felty syndrome are multifactorial and not fully elucidated. The interplay between autoimmunity, inflammation, and bone marrow dynamics contributes to the hematologic manifestations observed in this condition. 

Case Presentation 

A 58-year-old male patient visited physician’s office with complaints of a nonhealing skin ulcer on the left leg. The patient has a past medical history of rheumatoid arthritis for the last 10 years and is on methotrexate and low-dose prednisone. The patient has a family history of rheumatoid arthritis.  

 

On examination, the shallow, erythematous ulcer is seen on the left leg above the ankle laterally. The ulcer is 4 x 2 cm and has irregular borders (Figure 1). 

 

His vitals include a body temperature of 99.5°F, blood pressure of 130/86 mmHg, pulse rate of 90 bpm, respiratory rate of 20 breaths per minute, and normal heart sounds. He also observed a weight loss from 72 kgs to 68 kgs in the past two months.  

 

Palpation of the abdomen revealed signs of hepatosplenomegaly. Laboratory investigation indicated a neutrophil count of 1800/microliter, hemoglobin at 8 g/dL, blood glucose levels at 95 mg/dL, platelet count at 100,000/microliter, elevated liver enzymes, normal kidney profile, and CRP of 22 mg/L. On further examination, ultrasonography of the abdomen revealed an enlarged liver and spleen. The skin biopsy of the ulcer’s surroundings revealed vasculitis. 

 

Figure 1 

Case Management

To establish a definitive diagnosis and differentiate Felty syndrome from other conditions, a comprehensive medical history, physical examination, laboratory tests (including complete blood count, rheumatoid factor, and autoantibody testing), and imaging studies were performed. The patient was administered G-CSF during the hospital stay. TNF inhibitors were given to the patient; they were withdrawn immediately after the neutropenia worsened, and the patient started with rituximab as a second-line therapy. The general Surgery department was consulted on the case for potential splenectomy.

Discussion

Available data indicates that about 1-3% of rheumatoid arthritis patients experience Felty’s syndrome, with an estimated prevalence of approximately 10 cases per 100,000 individuals [4]. Due to the autoimmune reaction and limited treatment options, the prognosis appears to be unfavorable [2]. A thorough differential diagnosis was crucial for accurate identification and appropriate management. Chronic infections, such as vasculitis, can cause splenomegaly and neutropenia. Other autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) or systemic sclerosis, may present with joint symptoms and hematological abnormalities [2,5]. Chronic lymphocytic leukemia (CLL) and other hematological disorders can cause splenomegaly and abnormalities in blood cell count [2,5]. Sarcoidosis, a multisystem inflammatory disease, may involve the joints, spleen, and hematological system [2]. Systemic amyloidosis can affect multiple organs, leading to joint symptoms, splenomegaly, and abnormalities in blood counts. Lymphomas or other malignancies can present with joint symptoms, splenomegaly, and hematological abnormalities [2]. Chronic granulomatous disease is a rare inherited disorder that affects the immune system and can lead to recurrent infections, granuloma formation, and organ involvement [2, 6]. Certain medications, such as methimazole or clozapine, can cause neutropenia and may need to be considered in the differential diagnosis [7]. 

 

In the above-mentioned case, immunosuppressive therapy might have led to neutropenia. Methotrexate is a disease-modifying antirheumatic drug (DMARD) commonly used to treat rheumatoid arthritis (RA) and other autoimmune conditions. Neutropenia is a known side effect of methotrexate [8]. Regular monitoring of blood counts is typically done in patients taking methotrexate to detect and manage any potential neutropenia. Prednisone is a corticosteroid that is often used to reduce inflammation and suppress the immune system in various medical conditions, including autoimmune diseases. While neutropenia is not a common side effect of prednisone, high doses or prolonged use of corticosteroids may lead to changes in blood cell counts, including a decrease in neutrophil levels. However, prednisone is not the primary cause of neutropenia in the same way as some other medications. 

 

Although the neutrophil count of this patient was a little high (1800/ microliter) to include it as a triad of Felty Syndrome, a long-standing history of RA and splenomegaly were the confirmatory diagnostic criteria.  

 

To manage the symptoms of the patient, different therapies can be adopted based on the patient’s signs and symptoms. First and foremost, rheumatoid arthritis should be treated with disease-modifying anti-rheumatic drugs. Medications such as methotrexate, sulfasalazine, and leflunomide are commonly used to control the inflammation and progression of rheumatoid arthritis. TNF inhibitors (e.g., etanercept, adalimumab) and other biological drugs may be prescribed for individuals with severe RA to target specific pathways involved in the inflammatory process [9]. Neutropenia can be treated by administering G-CSF [10]. Splenectomy can be the last resort in the management [11]. 

 

In one of the case report presentations, a 28-year-old female patient was treated with systemic acyclovir and Abreva ointment for lip ulcers and adalimumab, hydroxychloroquine, and azathioprine for RA. She received additional supplementation of vitamins B1, B6, and B12. While in the hospital, intravenous azithromycin was initiated to address pneumonia and urinary tract infection (UTI). This patient demonstrated the triad; however, this patient has had a history of RA for the last three years. The patient recovered well [12]. 

 

In another case, a 35-year-old female patient was treated with methotrexate and hydroxychloroquine along with folic acid, calcium, and vitamin D supplementation. However, this patient did not have a long-standing history of RA as per the available record [13].

Conclusion

A patient with Felty Syndrome can present with uncommon and variable symptoms. However, a thorough diagnostic evaluation is beneficial to confirm the diagnosis. Different treatment approaches can be adopted once the diagnosis is confirmed. The mainstay treatment is the management of underlying causes, such as all the symptoms related to rheumatoid arthritis, neutropenia, and splenectomy as a last resort.  

References

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Acknowledgment 

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Funding

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Author Information

Hiremath S, BAMS, MBA Clinician, Editor, medtigo 

Sindhoori T, PharmD, Author, medtigo

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Conflict of Interest Statement

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Additional Information

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DOI

10.5281/zenodo.10603083

Cite this Article

Hiremath, S., & Sindhoori T. (2023). Felty Syndrome in long-standing rheumatoid arthritis: A Case Report. medtigo Journal, 1(1). https://doi.org/10.5281/zenodo.10603083

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