Felty Syndrome - Symptoms, Diagnosis, Treatment and Complications

Introduction:

The immune system protects the body against foreign invaders like bacteria, viruses, fungi, and parasites. The reaction that happens within the body, which activates the immune cells to defend against the pathogen, is called the immune response. Sometimes the immune system mistakenly attacks the body cells. This condition is called an autoimmune disease. There are various autoimmune diseases, most of which occur with an unknown cause.

What Is Felty Syndrome?

Felty syndrome is an autoimmune disease that exhibits symptoms without a definitive cause. The condition was first discovered in 1924 by an American physician, Augustus Roi Felty, at Johns Hopkins Hospital, and later in 1932, Hanrahan and Miller described the condition and termed it Felty syndrome. The condition is otherwise known as Chauffard-Still-Felty-Syndrome since it was analogous to the disease described by Still and Chauffard.

What Is the Pathophysiology of Felty Syndrome?

The exact pathophysiology of Felty syndrome is unclear and likely multifactorial, involving humoral and cellular immune mechanisms affecting neutrophil survival and proliferation. Neutropenia may result from inadequate production due to bone marrow infiltration by cytotoxic lymphocytes and increased sequestration from splenomegaly. A case-control study found that 73 percent of Felty syndrome patients had IgG Anti-G-CSF, suggesting G-CSF hyposensitivity and high levels of G-CSF might cause neutropenia. Autoantibodies binding to deaminated histones and NETs also contribute to neutrophil sequestration. Similarities between Felty syndrome and chronic large granular lymphocyte (LGL) leukemia suggest a common pathologic link, with both conditions featuring RA and elevated Fas ligand levels.

What Are the Signs and Symptoms of Felty Syndrome?

Felty syndrome is characterized by a triad of:

• Rheumatoid arthritis.

• Enlargement of the spleen.

• Low neutrophil count (a type of white blood cell important for immune response).

Patients often complain,

• Pain, stiffness, and swelling in the joints mostly affect the upper and lower limbs.

• Pain and diffuse expansion in the abdomen (stomach region).

• Recurrent infection.

• Fever.

• Swollen lymph nodes.

• Leg ulcers.

• Skin pigmentation.

• Loss of appetite and weight loss.

• Weakness and fatigue.

Clinical findings are:

• Damage to the nerves, usually in the hands and legs.

• Inflammation in the layers of the eyeball.

• Anemia.

• Inflammation of the blood vessels.

• A decreased platelet count affects the clotting mechanism.

How Does Felty Syndrome Develop and Progress?

• Felty syndrome involves immune mechanisms that produce defective neutrophils, resulting in a decreased concentration of mature neutrophils in the blood. The loss and destruction of neutrophils increase the risk of developing chronic infections.

• In rheumatoid arthritis, the immune system attacks the body’s tissues in the joints. The damage to the healthy tissues induces inflammation and fluid collection in the joints and causes swelling. Slowly, there is a decrease in the joint space, and as the disease progresses, the bones in the joints get fused, and the mobility is completely occluded.

• The increased need for the production of white blood cells causes hyperactivity in the spleen and ultimately leads to spleen enlargement. It is more of an inflammatory condition.

How to Diagnose Felty Syndrome?

The following clinical evaluation and detailed investigations are used to diagnose Felty syndrome:

• Medical History and Physical Examination: Physicians may evaluate the presence of rheumatoid arthritis and its severity, ulcers, lymph node enlargement, and nodules in the skin.

• Blood Test: Complete blood count shows an absolute decrease in the neutrophil, which is a hallmark sign of Felty syndrome. Also, there is a low number of red blood cells and platelets in the bloodstream. Laboratory findings also exhibit the characteristic presence of certain antibodies and proteins associated with rheumatoid arthritis.

• Imaging Techniques: X-rays are used to visualize severe joint destruction. Ultrasound and MRI (magnetic resonance imaging) scans can show an enlarged spleen and help measure the dimensions.

The normal dimension of the spleen in adults is about 4.33 inches. Poulin et al. described splenomegaly (spleen enlargement) based on the size of the spleen.

• Moderate: If the dimension is between 4.33 and 7.87 inches.

• Massive: If the dimensions are more than 7.87 inches.

Splenomegaly can also be defined by weight as follows,

• Normal: Averagely around 6.07 ounces.

• Mild: If the spleen weighs between 14.29 and 17.86 ounces.

• Moderate: If the spleen weighs between 17.86 to 35.71 ounces.

• Massive: If the spleen weighs more than 35.71 ounces.

Biopsy: Bone marrow aspiration and biopsy can show immature blood cells. Also, it is used to rule out other diseases associated with blood.

How to Treat Felty Syndrome?

The main aim of treatment for Felty syndrome is to control underlying arthritis and manage neutropenia (less neutrophil count) to prevent infections.

• Painkillers - NSAIDs (non-steroidal anti-inflammatory drugs), steroids, physiotherapy, occupational therapy, DMARD (disease-modifying antirheumatic drugs), and immunosuppressive drugs are suggested to improve arthritic conditions.

• Granulocyte Colony-Stimulating Factor (G-CSF) Therapy - Synthetic growth hormones to bring a significant increase in the absolute neutrophil count.

• Splenectomy (Removal of the Spleen) - It gave a marked improvement in neutrophil count. This surgical procedure was first suggested and tried by Hanrahan and Miller in 1932, who found a marked improvement in the clinical findings of Felty syndrome.

• Multiple Blood Transfusions - This may be required to combat fewer red blood cells and platelets.

• Monoclonal Antibody Therapy - This is a form of immunotherapy to attack the specific cells in the body.

• Gold Therapy - This was used in the olden days but discontinued owing to its extensive side effects.

What Are the Complications of Felty Syndrome?

• One of the most important complications of Felty syndrome is life-threatening recurrent infections, especially of the respiratory tract.

• Splenic rupture and internal bleeding.

• Increased risk of blood cancer (particularly non-Hodgkin’s lymphoma).

• Acute exacerbation of the underlying autoimmune disorder.

• Elevates the pressure in the veins of the liver and may result in bleeding along the lining of the gastrointestinal tract.

Can Felty Syndrome Be Fatal?

Individuals with Felty syndrome generally have a poorer prognosis than those without extra-articular RA symptoms. Neutropenia, marked by low neutrophil counts, increases vulnerability to severe bacterial infections and life-threatening complications. Additionally, there is an elevated risk of developing cancers like non-Hodgkin’s lymphoma and other hematological malignancies in those with Felty syndrome.

What Is the Prognosis of Felty Syndrome?

Since the introduction of MTX and biological treatments, the severity and extra-articular manifestations of RA have decreased. G-CSF has reduced the need for splenectomy in chronic neutropenia. A pre-MTX study showed a 36 percent 5-year mortality in Felty syndrome, mainly due to infections. Advanced treatments have since significantly improved the Felty syndrome prognosis.

Conclusion:

Felty syndrome is a rare disease and requires an interdisciplinary team of doctors to manage the condition effectively. Early diagnosis and treatment can avoid potential complications since the consequence of treatment delay in Felty syndrome can be fatal. Patients with rheumatoid arthritis must be frequently screened for recurrent infections, internal bleeding, and abdominal pain, especially in the spleen region. The treatment outcome for Felty syndrome depends on the severity of the symptoms and the patient's overall health. However, the collaborative approach of the physicians and patient compliance will give better treatment results.