Felty Syndrome is a rare autoimmune disease. It is caused by complications in seropositive rheumatoid arthritis (RA) and occurs extra-articularly (occurs outside a joint).Patients of felty syndrome usually experience symptoms like enlarged spleen (splenomegaly) and an abnormally low levels of neutrophils (type of white blood cell) (neutropenia).¹ Additionally, felty syndrome patients may suffer from serious and repeated infections.² Most felty syndrome patients are asymptomatic.³ However, if patients experience symptoms, living life with Felty syndrome can be very difficult. Patients of Felty syndrome often live in pain and struggle to function on a day to day basis. In this article, we are going to discuss what Felty Syndrome is, its symptoms, cause, effect on quality of life and ways to improve felty syndrome patients’ quality of life. 

Read on: In the following section, we are going to discuss the possible cause, symptoms, diagnosis, and the impact of Felty syndrome on  quality of life. 

Causes and risk factors

There is a lot of debate on the cause of Felty syndrome and there are no confirmed causes of the disease. However, factors like genetic, autoimmunity and existing chronic RA are estimated to play a role in the cause of Felty syndrome.⁴ Genetically, there is strong clinical evidence proving that the HLA-DR4 allele (human leukocyte antigen-DR4) increases the risk of developing anti-CCP antibodies that identifiesRA .⁵ It is known that people with anti-CCP antibodies have a higher chance of developing more severe RA, especially RA that affects other parts of the body besides the joints.⁶

Additionally, there is also evidence proving that having two copies of the DRB1804 genes are linked to a more severe RA. Studies show that there is a strong link between the gene and Felty syndrome.⁷ 

In terms of autoimmunity, Felty syndrome is believed to be an autoimmune disorder. When allergy, blood disorder or unknown immune disturbance occurs, the autoantibodies bind against white blood cells called neutrophils. This causes an abnormally low count of neutrophils.¹ 

Symptoms

The symptoms of felty syndrome are often long and severe. It typically develops around 16 years after the onset of long-term RA. Felty syndrome also typically affects females more than males. It is estimated that felty syndrome affects females three times more than males. Additionally, it is also more likely to affect more Caucasians than African Americans.⁸ The symptoms of felty syndrome can include:^1,9 

• Enlarged livers (hepatomegaly)
• Rheumatoid nodules
• Swollen lymph nodes (lymphadenopathy)
• Inflammation
• Fatigue
• Fever
• Weight loss
• Loss of appetite
• Skin discoloration causing brown pigmentation on the leg
• Anemia (insufficient healthy red blood cells)
• Sjögren’s disease
• Pulmonary fibrosis
• Pleuritis
• Peripheral neuropathy

Diagnosis

There are multiple ways to diagnose felty syndrome. The diagnosis of felty syndrome usually includes: the presence of RA, an enlarged spleen, and an unusually low neutrophil count.⁹ Common ways include complete blood count, serology, imaging, bone marrow biopsy and histology.¹

• Complete blood count: This method measures the count and size of hemoglobin, white blood cells and platelets.¹⁰ It is known that patients with Felty syndrome have an absolute neutrophil count of <2000/µL. This increases their risk of infections
• Serology: The presence of positive rheumatoid factor (RF) and anti-CCP, are indicators of Felty syndrome. Additionally, HLA-DR4 and anti-histone are also possible indicators¹¹ 
• Imaging: Radiographs of small peripheral joints are indicators of Felty Syndrome. Additionally, ultrasound images of the spleen can show if there is any enlargement of the spleen

Treatment 

The treatment of Felty syndrome mainly involves the prevention of infections by treating neutropenia and the treatment of rheumatoid arthritis​​.

Treatment of felty syndrome usually involves steroids, methotrexate, and monoclonal antibody therapy.¹

To increase neutrophil count, low-dose oral methotrexate (MTX) with folic acid is used as the first-line treatment for 4-6 weeks. Leflunomide and biologic agents like rituximab will be used if MTX is ineffective. If the infection persists, granulocyte-colony stimulating factor (G-CSF) is used.¹²

If treated properly, the mortality rate of felty syndrome shows significant decrease. Before treatment, there is a 5-year mortality of 36%.¹ Meanwhile, after diagnosis, there is a mortality rate of 25% in 5 years.¹³ It is therefore important that patients seek medical help if they are experiencing possible symptoms to reduce the risk of death.

Quality of Life Impact of patients suffering from felty syndrome

Impact on physical health

Infections: 

Felty syndrome has a huge impact on the patient's physical health. The most commonly known one is an increased risk of pathogenic infections. Felty syndrome patients often suffer from recurring infections. This is mainly due to neutropenia (low neutrophil count) in their system. Possible severe side effects like increased mortality may occur as a result of this.¹⁴ In an experiment tracking 32 felty syndrome patients, 8 died within the span of 0.3 to 14.8 years of follow up.¹⁴ Infections could also cause severe disability, skin ulcers, immunodeficiency and more.¹⁵ Patients may also experience impaired phagocytosis and intracellular killing¹⁶, which causes an even higher risk of infections recurring, causing massive pain to the patients. The frequency of infections also increases due to this. The common areas that infections affect, include the skin, mouth and respiratory tract. This causes irritation, itchiness, breathing problems and pain.¹⁷ 

Fatigue and weakness:

Fatigue and weakness is also a known symptom in Felty syndrome. This is due to T-LGL lymphocytosis (abnormal increase in a type of white blood cell called  Large granular lymphocytes) found in felty syndrome patients.T-LGL lymphocytosis is associated with low white blood cell counts, anemia, weight loss, night sweats and an enlarged spleen.¹⁸ These symptoms reduce the day to day living quality of patients as they are unable to enjoy highly physical activities and would have a lower sleeping quality. Patients also require more rest than the average person, causing a lower satisfaction in life. 

Joint inflammation is also common in Felty syndrome. Such inflammations can cause mobility issues and severe pain. Due to severe inflammation, patients may have stiff, swollen and painful joints, especially on their hand, feet and arms.¹⁹ Patients may struggle to walk and suffer from mobile issues due to the pain and stiffness. The limitation of physical ability may also prevent patients from employment, a normal social life and ability to engage in day to day activities. 

Felty syndrome may also cause emotional stress and negative psychological impact on the patients. Felty syndrome is considered a chronic illness. This means that the illness is incurable and long-lasting. When facing medical care, it may be defeating to know that there is currently no treatment for the disease. In addition, as felty syndrome could be deadly, there is an emotional stress of the patient's own mortality. These factors may all cause emotional distress. 

Conclusion

The symptoms and experience of felty syndrome may negatively affect one's quality of life massively. It is important for us to support felty syndrome patients as a society. Medical support and education of the syndrome to long-term rheumatoid arthritis (RA) patients is essential as they are at high risk of Felty syndrome. If symptoms of felty syndrome are experienced, patients should seek medical help as soon as possible to reduce symptoms. Additionally, it is also important for family and friends to understand the treatment and symptoms of the illness to assist patients in coping with the disease. With the cooperation of patients and medical professionals like doctors and occupational therapists, Felty syndrome patients can live a relatively normal life.