What is Felty Syndrome?
Felty syndrome, also known as Chauffard-Still-Felty disease, is a rare condition related to rheumatoid arthritis (RA). Rheumatoid arthritis is a disorder that causes joint inflammation and pain. People with Felty syndrome also have two other conditions: neutropenia and splenomegaly. Neutropenia means you have too few neutrophils, a type of white blood cell that helps fight infection. Splenomegaly means the spleen (an organ that helps filter your blood and fight infection) is larger than normal. More than 90% of people with Felty syndrome have a genetic marker called HLA-DR4.
An American doctor named Augustus Felty first described this syndrome in 1924. He wrote about five patients who had long-term joint inflammation, enlarged spleens, and very few neutrophils. An official name for this condition wasn’t given until 1932, when another pair of doctors noted the benefits of spleen removal in a patient with these symptoms.
You can still be diagnosed with Felty syndrome if you don’t have all three conditions. However, neutropenia is a key feature of this syndrome and must be present for the diagnosis. Felty syndrome can be hard to identify because it’s rare, and the symptoms can vary. The condition requires meticulous clinical observation and diagnostic skills. It also calls for cooperation among various healthcare professionals—including doctors, nurse practitioners, nurses, pharmacists, and others—for comprehensive management.
What Causes Felty Syndrome?
There is significant evidence suggesting that a specific genetic component, known as the HLA-DRB1 allele shared epitope, may raise the risk for the development of anticyclic citrullinated peptide (CCP) antibodies. Simply put, these antibodies are a sign of Rheumatoid Arthritis (RA), a chronic inflammatory disorder that primarily affects the joints. In fact, they are very specific to RA, found with a 96% accuracy in patients with this disease.
The presence of both rheumatoid factor (a protein produced by the immune system that can cause joint inflammation) and anti-CCP antibodies can increase the risk of developing extra-articular RA, a more severe form of the disease that can affect organs other than joints.
The HLA-DRB1 gene includes different versions like DRB1*01 and DRB1*04. Having two copies of the DRB1*04 version is associated with a more severe form of RA that leads to significant joint damage. A large study involving various centres observed a strong link between the DRB1*0401 version of the gene and Felty syndrome, a rare complication of RA that involves joint destruction and an enlarged spleen. But the study found no link between extra-articular RA and other genetic components like HLA-DQB1 alleles and combined DRB1-DQB1 traits, highlighting the specific importance of the HLA-DRB1 gene.
Risk Factors and Frequency for Felty Syndrome
Felty syndrome is a condition that is found in about 1% to 3% of people with rheumatoid arthritis (RA). However, the likelihood of developing Felty syndrome has been decreasing due to advances in arthritis medication, like methotrexate and biologics. As a result, the actual number of cases is quite low.
This syndrome typically presents about 16.1 years after a person is diagnosed with RA. Those with a family history of RA have a greater risk of developing Felty syndrome. Also, it has been found that there is a strong link between RA and a genetic marker known as HLA DR4 in patients with Felty syndrome.
The distribution of Felty syndrome is similar to that of RA. It is more common in:
- Females, with women being three times more likely to be affected than men
- People in their middle years
- People of White descent as compared to non-White populations
Signs and Symptoms of Felty Syndrome
Felty syndrome is a severe type of rheumatoid arthritis (RA). It usually affects patients with longstanding, aggressive RA. However, it might sometimes be detected before the arthritis symptoms show up. Even if there are no clear signs of Felty syndrome at the beginning, most patients’ x-ray scans will show signs of this disease. Up to 75% of the time, fluid build-up in the joints known as synovial effusions might also be seen.
Felty syndrome is usually identified when a patient gets an infection because it often doesn’t show any other symptoms. The most common infections people with Felty syndrome get are skin and respiratory infections. It’s also possible for patients to experience other issues beyond arthritis. These could include:
- Rheumatoid nodules (74% of patients)
- Enlarged liver (68% of patients)
- Swollen lymph nodes (42% of patients)
- Sjogren syndrome, a condition that affects the glands that make tears and saliva (48% of patients)
- Pulmonary fibrosis, a lung disease that makes it hard to breathe (50% of patients)
- Pleuritis, inflammation of the tissues that line the lungs and chest cavity (22% of patients)
- Peripheral neuropathy, a condition that causes weakness, numbness and pain from nerve damage in the hands and feet (14% of patients)
- Leg ulcers (16% of patients)
System-wide symptoms, such as fever and weight loss, might also occur. While most patients have an enlarged spleen (splenomegaly), it’s not required for a diagnosis. Some patients might also experience idiopathic non-cirrhotic portal hypertension, which could lead to bleeding from enlarged veins in your esophagus or stomach.
Testing for Felty Syndrome
If your doctor suspects that you might have Felty syndrome, they may order a complete blood count. This test involves counting the different types of cells in your blood. They will particularly look for a low absolute neutrophil count, a type of white blood cell. If this count is less than 2000/µL, it’s a key indicator of Felty syndrome and suggests an increased risk of bacterial infections. Sometimes, a doctor can diagnose Felty syndrome sooner if they’re already monitoring your blood counts for another reason, like tracking the side effects of a medication.
When it comes to Felty syndrome, the correlation between spleen enlargement and degree of neutropenia is not established. Anemia and a low platelet count may be observed if your spleen is enlarged. Anemia of chronic inflammation is found in almost all patients with Felty syndrome. This disease condition is also more commonly linked with autoimmune hemolytic anemia (where our body destroys its red blood cells) compared to rheumatoid arthritis.
In addition to this, your doctor may also conduct certain serological tests. These tests detect the presence of certain antibodies in your bloodstream. In Felty syndrome, these antibodies can be rheumatoid factors or anti-CCP. The presence of antinuclear antibodies, anti-histone antibodies, and HLA-DR4 can also be detected. The detection of anti-histone antibodies in someone with rheumatoid arthritis implies they may have Felty syndrome.
Imaging techniques can also be used to assist in the diagnosis. Basic X-rays of your smaller joints may reveal significant joint damage. Ultrasounds or radionuclide scans of your spleen may be used to detect an enlarged spleen.
In some cases, a bone marrow biopsy may be performed. This is a process where a small sample of bone marrow is extracted for examination. Most individuals with Felty syndrome would show increased production of certain cell types in the bone marrow, also described as “maturation arrest”. This test helps rule out the possibility of other diseases like LGL leukemia. The sample obtained can be further studied for the identification of specific cells that could help in diagnosing LGL leukemia.
Apart from this, examination of the spleen tissue, typically during an autopsy or after its removal, would show nonspecific results such as congestion in venous sinusoids, increased activity of reticular cells, and germinal cell hyperplasia.
Treatment Options for Felty Syndrome
Felty syndrome treatment primarily focuses on controlling the root cause, which is Rheumatoid Arthritis (RA), and addressing the low white blood cell count (neutropenia) to prevent infections. The goal of the treatment is to increase the white blood cell count (specifically, granulocytes) to over 2000 per microliter of blood. While a low white blood cell count isn’t a problem in itself without the presence of infections, it can help doctors adjust the RA drug treatment accordingly. If treating RA improves the white blood cell count, it suggests that Felty syndrome is involved. Patients with a low white blood cell count should get thoroughly checked for signs of infection. Symptoms affecting the entire body should be treated promptly.
It’s important for patients with a low white blood cell count to maintain good dental and oral hygiene, receive timely age-specific vaccines, and prevent infections, which involve treatment with wide-spectrum antibiotics. Consulting an infectious disease specialist can be helpful in this case.
There aren’t any randomized control studies available to direct Felty syndrome treatment, so most guidance is from observational studies. One recommended treatment method involves low-dose oral methotrexate (MTX) alongside folic acid, which aids in countering any potential negative effects of MTX, particularly in the liver, bone marrow, and gastrointestinal tract. This treatment has proven helpful in increasing white blood cell count and preventing repeat infections.
Occasionally, other RA medications are reported to help. One case study described successful use of leflunomide in a patient who developed an allergic reaction to etanercept, another RA drug, while on MTX therapy. Back in the day, gold therapy was administered to patients with Felty syndrome, but due to many negative side effects, it’s no longer in use. Cyclosporine has shown some effectiveness but isn’t usually an option because safer alternatives are available.
Biological drugs, specifically rituximab – a monoclonal antibody against CD20 antigen – have demonstrated improvement in patients who failed to respond to an adequate trial of nonbiologic RA medications.
Corticosteroids, another class of medication, can be used to quickly increase the white blood cell count in patients with Felty syndrome, but due to its immunosuppressive effect, long-term use is generally not advised. For patients with absolute neutrophil count (ANC) of less than 1000 per microliter of blood, who suffer severe and recurring infections, Granulocyte-colony stimulating factor (G-CSF), a protein that stimulates the bone marrow to produce more white blood cells, is typically used. If these patients still don’t respond to RA drugs and rituximab, G-CSF might be administered until the patient’s white blood cell count increases.
In extreme cases where medical treatment doesn’t work and when serious infections keep recurring due to a low white blood cell count, removing the spleen (splenectomy) might be considered. Other rare reasons for undergoing splenectomy are severe anemia requiring multiple transfusions and severe bleeding due to low platelet count unresponsive to usual treatment. The low white blood cell count might recur after the operation in one-fourth of the cases. However, with the advancement of drug and biological therapies, the surgical approach is now limited in its application.
What else can Felty Syndrome be?
: It’s important for doctors to consider certain other conditions that may appear in patients with Rhematoid Arthritis (RA) who are also experiencing neutropenia (a decrease in a type of white blood cell). One of these is LGL leukemia, sometimes referred to as “pseudo-Felty syndrome”. This can look a lot like another condition known as Felty syndrome. The two conditions can be told apart using specific tests, such as cell marker detection and bone marrow biopsies, which will show an increase in specific cell types if the patient has LGL leukemia. Many medical professionals believe these two conditions are different points on a spectrum of the same disease.
Doctors should rule out other potential causes of neutropenia and splenomegaly (an enlargement of the spleen). These could include viruses, like Epstein-Barr virus and HIV, other autoimmune disorders, like lupus, and medications that the patient may be taking. Certain drugs can cause a decrease in white blood cells, and in these cases, a temporary pause in the medication can sometimes reveal whether that is the cause of the neutropenia.
The most potentially significant causes to contemplate in patients with RA experiencing neutropenia, are:
- LGL leukemia
- Certain medications
- Viral infections such as Epstein-Barr virus and HIV
- Other autoimmune conditions, such as lupus
These could present with similar symptoms, so careful consideration and testing are essential for an accurate diagnosis.
What to expect with Felty Syndrome
The severity and additional symptoms related to Rheumatoid Arthritis (RA), a chronic disorder affecting the joints, have been slowly decreasing. This is thanks to the availability of treatments like Methotrexate (MTX) and biological treatments.
Granulocyte colony-stimulating factor (G-CSF) is another treatment used for chronic neutropenia – a disease causing a low number of white blood cells. With the use of G-CSF, there’s less need for splenectomy, a surgical procedure to remove the spleen.
A study conducted before MTX was available reported a 5-year mortality rate of 36% in patients with Felty syndrome. Felty syndrome is a disorder that involves RA, neutropenia, and an enlarged spleen. The most common cause of death was infection.
Currently, there isn’t much recent data about the prognosis (or the likely course or outcome of a disease) of Felty syndrome. However, the development of advanced treatment options has considerably improved the outcome for patients with this condition.
Possible Complications When Diagnosed with Felty Syndrome
Felty syndrome’s main complication is intense or repeated infections, especially in the respiratory tract and skin, due to a decrease in a type of white blood cell called neutrophils. Other complications may include anemia, which is a low red blood cell count due to accumulation of blood cells in the spleen, and severe bleeding due to extreme drops in platelet count. There is also the possibility of severe bleeding caused by high blood pressure in the portal vein system (the veins that carry blood to the liver). Procedures like spleen removal, which is done to treat persistent neutropenia, can increase the chance of post-surgical infections, which have even led to death in some instances. G-CSF, a treatment used to stimulate the growth of white blood cells, carries a minor risk of worsening existing autoimmune disorders.
Common Complications:
- Severe or recurrent infections
- Anemia due to blood cells collection in the spleen
- Bleeding caused by severe drop in platelet count
- Severe bleeding caused by high blood pressure in the portal vein system
- Increased risk of infections after spleen removal surgery
- Possible worsening of autoimmune disorders due to G-CSF treatment
Preventing Felty Syndrome
Felty syndrome is a rare disease, but it is important to consider as a possible cause in anyone who shows up with symptoms of rheumatoid arthritis (RA) and a low white blood cell count, called neutropenia. This consideration is vital because any delay in addressing it could have serious, even deadly, consequences. It’s also important to note that if a patient has an active infection, the low white blood cell count which is a symptom of the syndrome might not be apparent.
Currently, there isn’t a specific treatment for Felty syndrome. Since the disease is rare, there haven’t been enough patients to conduct thorough studies on different treatment options. Therefore, doctors base their recommendations on a handful of observational studies. This lack of solid data makes it challenging to decide on the best course of action, especially during emergencies or in settings where medical resources are limited. Also, it’s a real challenge for patients whose low white blood cell count doesn’t improve with treatment.
For those not in a critical condition, anyone with a low white blood cell count is advised to maintain good oral and dental hygiene and to regularly monitor their medication meant to control rheumatoid arthritis. A key aim is to improve the white blood cell count to prevent future infections.