Overview

Felty's Syndrome (FS) is a rare complication of rheumatoid arthritis (RA) that was first described by Dr. Augustus Felty in 1924. This condition is characterised by three typical symptoms: seropositive RA with severe joint involvement, low level of white blood cells (neutropenia), and an enlarged spleen (splenomegaly). 

However, at least three of this triad are not relevant for the diagnosis. Furthermore, some subjects with FS do not present with an enlarged spleen and prominent joint involvement, while some are asymptomatic. Neutropenia is the hallmark symptom of FS -It is key for diagnosis. FS can be a potentially life-threatening and serious systemic condition due to an increased risk of infection during an immunosuppressed state of RA.

The usual time of onset of Felty syndrome is between the ages of 50-70 years. Typically, patients with progressive rheumatoid arthritis have had symptoms a decade or more before Felty syndrome begins.¹

Prevalence

Around two per cent of people living with RA will go on to develop Felty syndrome. Just like RA, Felty syndrome is also three times more likely to affect females than it does males. Those affected by this version of RA are almost always going to be seropositive, testing positive for the rheumatoid factor antibody; FS seldom develops in seronegative individuals.²

Causes

Not much regarding the exact cause of Felty syndrome is understood. It is rather understood to likely involve several factors, including increased genetic susceptibility and autoimmunity, for unknown reasons. Most people who have FS have a certain genetic marker, human leukocyte antigen DR4 (HLA-DR4), which increases a person's susceptibility to an unusual presentation or extra-articular presentation of rheumatoid arthritis.

In such patients, an autoimmune response to neutrophils may lead to the development of drug-related neutropenia associated with FS. Regardless of the exact cause of FS, research has identified that the syndrome occurs in a small percentage of patients with leaky gut syndrome, especially in patients who have been affected by the disease for more than 10 years and specifically for those who have a more severe version of the syndrome.³

Clinical presentation

The first symptoms in most cases are the RA-related ones.^2,4 These include:

• Joint pain
• Joint Swelling
• Joint rigidness

The extra-articular manifestations of RA in some patients, at some time in their lives, are as follows:

• Rheumatoid nodules: firm bumps under your skin close to your joints
• Swelling in your lymph nodes in your neck or armpits
• Enlarged liver, painful or tender to the touch
• Dry eyes and mouth
• Episcleritis: Redness and inflammation of the eyes
• Skin ulcers or sores on your legs
• Signs of bleeding under the skin
• Swelling in your lungs, hence making you short of breath
• Swelling in tissues and blood vessels surrounding your heart, leads to chest pains
• Fever
• Tiredness and general illness
• Loss of appetite or unexplained weight loss

Felty syndrome presents with other symptoms—indeed, sometimes before the symptoms of RA—and is composed of these three features:

• Chronic infections: cold, shock to the stomach, various pustules on the skin
• Swollen spleen that is tender to touch or palpated
• Abnormal skin discolourations

It is possible to diagnose FS without manifested signs and symptoms. Blood tests and imaging tests may reveal evidence of RA, neutropenia, and splenomegaly even before you are symptomatic.

Associated Co-morbidities

There are chronic infections: colds, shocks to the stomach, different pustules on the skin, and. Despite the associated signs and symptoms accompanying FS, other associated comorbidities can ensue as well. Infections are quite common, especially due to neutropenia, and these infections tend to occur in the skin and pulmonary tracts. Notably, neutropenia in FS can cause an increased risk for cancers, especially non-Hodgkin's Lymphoma. More importantly, hepatomegaly, lymphadenopathy, episcleritis, sicca syndrome, eyelid necrosis, pleuritic neuropathy, portal hypertension, liver involvement such as portal fibrosis or cirrhosis, and anaemia also results for those with FS.¹

Furthermore, FS symptoms such as splenomegaly are indicative of other complications: hepatic cirrhosis, brucellosis, visceral leishmaniasis, bacterial endocarditis, histoplasmosis, amyloidosis.

Diagnosis

FS in most cases is pointed out based on the patient's evaluation, history, presence of RA, neutropenia, and splenomegaly. Severe RA joint or spleen involvement appears not to be invariably present in FS; indeed, such features are not necessary for diagnosis. However, those symptoms are common characteristics of FS. Neutropenia with absolute neutrophil count <1500/mm3 is required for diagnosis^,.³ Other diagnostic tools are as follows:

Physical examination

• Palpate for splenomegaly
• Examine joints affected by RA
• Look for swelling lymph nodes
• Palpate for hepatomegaly

Investigations

• Full blood count
• Serological test
• Histologic examination
• Radiography
• Ultrasound
• CT scan
• Bone Marrow biopsy

Differential diagnosis

• RA
• Amyloidosis
• T-cell large granular lymphocyte leukemia (TLGL)
• Systemic Lupus Erythematosus (SLE)
• Cirrhosis
• Myeloproliferative Disease
• Non-Hodgkin's LymphomaSarcoidosis
• Sjogren Syndrome
• Tuberculosis (TB)⁵

Treatment 

Treatment of FS is directed toward relieving rheumatoid arthritis and reducing the risk of fatal infections. Long-term management includes the use of advisably disease-modifying anti-rheumatic agents such as methotrexate, hydroxychloroquine, and sulfasalazine. DMARDs can suppress the inflammation caused by RA. Most of these drugs boost the number of white blood cells and reduce splenomegaly for the optimal functioning of the immune system in fighting infections.³

Neutropenia may be treated with growth injections for granulocytes and possibly other medications, including rituximab and granulocyte colony-stimulating factor. Surgical removal of the spleen, or splenectomy, can so thrive the skirmish of FS; it's generally performed only in individuals whose initial therapies with medications are barely responsive. Finally, it is extremely necessary to identify the infections developed in the early stages and treat them rapidly in an attempt to avoid multiple complications developed afterwards. Treatment for infections mainly involves some form of antibiotics with the inclusion of other precautionary and supportive treatments. 

Prognosis

Both severity and extra-articular manifestations of RA have decreased with time after the advent of MTX and biological treatments for the control of disease activity in RA. The availability of G-CSF for the management of chronic neutropenia has increased the number of patients who do not require splenectomy. In one retrospective study conducted before the advent of MTX, Felty syndrome affected 5-year mortality and occurred at a rate of 36%, with infections being the most common cause of death. No information is available on the current prognosis of Felty syndrome. However, advanced treatment options have very much improved the prognosis for FS.⁶

Complications

The most important complication of Felty's syndrome is severe or recurrent infections, particularly of the respiratory tract and skin, due to neutropenia. Other complications include haemorrhage from severe thrombocytopenia and anaemia from splenic sequestration. Variceal bleeding can be a complication of portal hypertension. Treatment modalities like splenectomy for refractory neutropenia may enhance the risk of infections post-surgery and have seldom been fatal. G-CSF harbours the potential for causing an exacerbation of the underlying autoimmune disorder.⁶

Summary

FS is a rare complication of RA characterised by seropositive RA with severe joint involvement, a low white blood cell count (neutropenia) and an enlarged spleen (splenomegaly). FS develops with the highest frequency in women at ages 50 to 70 years, affects 2% of those with RA, and may be more frequent in women and AFAB individuals. In most cases, the aetiology of FS remains unknown but doubtless includes genetic susceptibility and autoimmunity. The diagnosis is based on RA, neutropenia, and some sort of splenomegaly combined; other symptoms include frequent infections, swollen spleen, and abnormal skin discolourations.

Treatment is directed at RA management as well as the reduction in risk for infection; treatment includes DMARDs, rituximab, GCS-F, and splenectomy. The outlook has drastically improved due to better treatment, and complications of severe infections, anaemia, haemorrhage, and variceal bleeding are reported to set in. Early detection and treatment of infections are of paramount importance to avert further complications.