Introduction

Rheumatoid arthritis (RA) is a long-term condition causing joints to become inflamed. As a result of the inflammation, joints in the hands, feet, and wrists become painful, swollen, and increasingly stiff. RA affects around 18 million people, most commonly affecting women over 55 years.

Felty syndrome (FS), first observed by Dr. Augustus Felty in 1924 in patients with chronic RA who had additional shared symptoms, is a rare disorder resulting as a complication of RA. FS is characterised by symptoms of RA, in addition to an enlarged spleen and depletion of first-response immune cells called neutrophils.¹ 

This article aims to explore both RS and FS and their relationship. Understanding the relationship between RA and FS is crucial for early diagnosis and prevention of severe complications like recurrent infections. This knowledge allows accurate treatment of FS, improving patient outcomes. Additionally, it provides insights into autoimmune mechanisms underlying both conditions, aiding in the identification of better treatment targets.

Understanding rheumatoid arthritis

Pathophysiology 

RA is an autoimmune disease caused by the immune system attacking joints. The disease develops due to complex interactions between several genetic, environmental, and immunological factors:

1. Mutations in HLA-DR4 and HLA-DR1 genes, responsible for presenting harmful germs (and self-proteins in autoimmune disease) to immune-response-activating T helper cells, reduce the ability of the immune system to distinguish between self and non-self. Consequently, the immune system becomes more prone to self-attack and causes RA. The likelihood of these mutations is increased with risk factors such as smoking, obesity, and air pollution
2. In RA, autoantibodies are produced. These autoantibodies are proteins that are generated in health to ensure any unhealthy cells are attacked and killed. However, in autoimmune conditions, such as RA, they are produced against healthy cells and attack the lining of the joints called synovium
3. This autoimmune attack leads to an influx of immune cells to the site of attack, called inflammation. Inflammation is responsible for the defining swelling, pain, and stiffness of the joints in RA
4. When inflammation occurs over 3 months or longer, it is considered chronic. Chronic inflammation leads to abnormal growth of synovial cells, causing the lining of the joints to thicken. Over time, the thickening synovial cells form a layer of tissue called a pannus, which can invade and erode cartilage and bone
5. As a result of pannus formation, joints become increasingly weakened, sore, swollen, and less mobile. The ongoing inflammation can also affect other structures within joints, such as tendons and ligaments
6. If RA is left untreated, inflammation can have a wider systemic effect. This includes complications of the heart and lungs and an increased risk of infection across the body

Symptoms and diagnosis

The early symptoms of RA include:

• Pain
• Stiffness
• Tenderness 
• Swelling or redness in one or more joint(s)

Diagnosing RA is a difficult process since there are no specific tests and the symptoms overlap with several other conditions. Typically, GPs carry out a physical assessment to observe swelling and movement of joints and assess symptoms, as well as blood tests and medical scans (including X-rays and MRI scans). If the GP suspects RA as a potential diagnosis, a referral to a rheumatologist (a specialist inflammatory disease doctor) is made.

Quality of life

Patients suffering from RA often have a reduced quality of life due to everyday, basic tasks becoming more painful. This can often lead to exclusion from society since reduced movement makes working, socializing, and relationships more difficult to manage, taking a toll on the mental health of patients.

Understanding felty syndrome

Definition and components of FS

FS is defined as an RA complication made up of three conditions 

1. Rheumatoid arthritis (as described above)
2. Splenomegaly- enlarged spleen
3. Neutropenia- low white blood cell count, specifically neutrophils, which are white blood cells required to initiate the first immune response

Pathophysiology of FS

Although the pathophysiology of FS is not fully understood, it is known underlying RA is required for its development. This alludes to the immune system dysfunction occurring in RA contributing to FS manifestation. 

Neutropenia is a hallmark symptom of FS and is a result of overactive blood filtering by the spleen trying to destroy cells that do not need to be destroyed. The increased immune response can also cause suppression of neutrophil development in the bone marrow, further contributing to neutrophil depletion. 

Additionally, the overactivity of the spleen causes it to enlarge. Although it is unclear why the spleen enlarges in the case of FS, it is thought to be in correlation with chronic inflammation and immune system responses. This, as well as neutropenia, contributes to an increased risk of infection as there are fewer white blood cells to initiate immune responses to pathogens entering the body and reduced control over responses that do occur.

Symptoms and diagnosis

The main symptoms of FS can be broken down by each of the defining manifestations:

1. RA, as previously described
2. Splenomegaly - discomfort or a feeling of fullness in the left upper abdominal region
3. Neutropenia- frequent or unusual infections, usually affecting the skin, lungs and mouth

A diagnosis of FS can be made by assessing a patient's medical history, looking for previous diagnoses of RA, and a physical examination to check RA symptoms. Blood tests can indicate levels of white blood cells and immune system markers to aid FS diagnosis. An ultrasound can also be performed to demonstrate spleen enlargement.

Treatment and management of FS

Treatment of FS is patient-dependent, varying on the symptoms present and the severity of the disease. RA symptoms are treated initially using methods including bed rest, physical activity, heat treatments, non-steroidal anti-inflammatory drugs (NSAIDs), and penicillamine. In extreme cases of FS, the spleen may be surgically removed (splenectomy) to rectify neutropenia and chronic infections associated with FS. However, the long-term consequences are unknown.

Prognosis and outcomes

The prognosis for FS largely depends on the management and treatment of the underlying RA; the more controlled and treated the RA, the better the outcome for FS. This is largely achieved by early detection and accurate treatment. With the appropriate care, FS patients can lead relatively normal lives; however, monitoring and medical attention from medical professionals may be required.

Treatment and medications have largely improved the life expectancy and quality of life for FS patients, allowing them to live normal and long lives. Due to the destruction of joints in FS patients, treatment can be lifelong to ensure deterioration does not progress, and regular physical activity is recommended to build up joint strength and health. Preventative measures, such as keeping on top of vaccinations and good hygiene practices in day-to-day life, mitigate the increased risk of infections seen in FS patients.²

Summary

• Overview of RA and FS: Rheumatoid arthritis (RA) is a chronic condition causing joint inflammation, primarily affecting women over 55. Felty Syndrome (FS) is a rare RA complication, first described in 1924, characterised by RA symptoms, an enlarged spleen, and a low white blood cell count
• Pathophysiology of RA: RA is an autoimmune disease where the immune system attacks joint linings due to genetic and environmental factors, causing chronic inflammation and joint damage and potential systemic effects on the heart and lungs
• Symptoms and Diagnosis of RA: RA symptoms include joint pain, stiffness, and swelling. Diagnosis involves physical exams, blood tests, and imaging, often leading to a rheumatologist referral for specialised care
• Understanding FS: FS includes RA, splenomegaly, and neutropenia, leading to frequent infections due to a low white blood cell count. Diagnosis involves medical history, physical exams, blood tests, and ultrasounds to check spleen size
• Symptoms and Diagnosis of FS: FS symptoms include those of RA, abdominal discomfort from splenomegaly, and frequent infections due to neutropenia. Diagnosis involves medical history, physical exams, blood tests, and ultrasounds to assess spleen size
• Prognosis and Management of FS: The prognosis of FS depends on effective RA management. Treatments include NSAIDs, physical activity, and possibly splenectomy. With proper care, FS patients can lead relatively normal lives, though they need ongoing medical attention to manage symptoms and prevent infections