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    Home > Active Ingredient News > Immunology News > Without a history of RA, can RA complications be considered?

    Without a history of RA, can RA complications be considered?

    • Last Update: 2021-05-22
    • Source: Internet
    • Author: User
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    *For medical professionals to read only for reference, neutropenia is a hallmark feature of Felty syndrome! In 1924, Dr.
    Augustus Felty from Johns Hopkins Hospital in the United States described Felty syndrome for the first time [1].
    The main clinical manifestations of the latter are rheumatoid arthritis (RA), neutropenia and splenomegaly.

    Felty syndrome is a rare and serious complication of long-term RA.

    So, what are the epidemiological and clinical features of the fabled Felty syndrome? How to treat? Epidemiological characteristics of Felty syndrome According to reports, the prevalence of Felty syndrome in RA patients is about 1% to 3%, and the prevalence in the population is estimated to be about 10 per 100,000.

    With the widespread use of RA treatment drugs such as methotrexate and biological agents, RA has been better controlled, and the incidence of Felty syndrome seems to have decreased [1-2].

    HLA-DR4 gene is closely related to Felty syndrome.
    HLA-DRB1 subtype is a risk factor for anti-cyclic citrullinated polypeptide (CCP) antibody positive, while RA patients with anti-CCP antibody and rheumatoid factor (RF) positive develop extra-articular The risk of performance increases.

    More than 90% of Felty syndrome patients can see HLA-DR4 positive [2-3].

    The early risk of Felty syndrome in men in RA patients is higher than that in women, but the overall incidence rate in women is three times that of men.

    The average age of onset of Felty syndrome patients is between 50 and 70 years old (21-76 years old).

    Patients with a positive family history of Felty syndrome are at increased risk [1-4].

    Due to the increased risk of serious infections in patients with Felty syndrome, the overall mortality rate is higher, and the prognosis is poor, of which infection is the main cause of death.

    This is consistent with the conclusion that the mortality rate increases when RA is complicated by extra-articular manifestations.

    However, some patients with Felty syndrome have spontaneous remission.

    Clinical features of Felty syndrome Although Felty syndrome usually occurs in long-term, severe, aggressive, and seropositive RA, the serious complications of this RA may not cause symptoms.

    Felty syndrome usually starts about 16 years after RA, and about 75% of patients have synovial effusion [1], but a small number of patients may have an onset time earlier than the diagnosis of RA.

    Most patients with Felty syndrome have no symptoms of arthritis when they are first diagnosed.
    These patients with no symptoms of arthritis may have joint imaging changes.

    Most patients can gradually develop arthritis symptoms of RA during the follow-up period, and the latter may even occur 10 years after the initial diagnosis [5].

    Most patients with Felty syndrome have splenomegaly, which can often be palpable on clinical examinations.
    Splenomegaly is related to the proliferation of lymphoid follicles and germinal centers, and the increase of plasma cells and immunoblasts [2].

    Some patients may also have idiopathic non-cirrhotic portal hypertension, which may be complicated by bleeding from esophageal varices.

    Patients with splenomegaly may have anemia and thrombocytopenia.

    During the development of the disease, many patients with Felty syndrome have systemic symptoms (fever, weight loss) or extra-articular manifestations, the latter including rheumatoid nodules (74%), liver enlargement (68%), and lymphadenopathy (42%) ), Sjogren’s syndrome (48%), pulmonary fibrosis (50%), pleurisy (22%), peripheral neuropathy (14%), leg ulcers (16%) [1].

    The absolute neutrophil count below 2×109/L is a hallmark feature of the diagnosis of Felty syndrome, which indicates an increased risk of bacterial infection.

    There is no correlation between splenomegaly and the degree of neutropenia.

    The initial manifestation of Felty syndrome patients is often a bacterial infection caused by neutropenia, and the most common sites of infection are the skin and respiratory tract.

    Neutropenia associated with Felty syndrome is the result of multiple factors, including isolation of neutrophils in the spleen (due to splenomegaly or hypersplenism), increased destruction of peripheral blood neutrophils, and bone marrow production of neutrophils Reduce (such as drug factors).

    Elevated levels of anti-granulocyte colony stimulating factor (G-CSF) antibodies can also lead to neutropenia.

    Serological examination results of Felty syndrome and RA are similar.
    Most patients with Felty syndrome have positive RF and anti-CCP antibodies, and may also have positive antinuclear antibodies and anti-histone antibodies.

    Therefore, even if there are no symptoms of arthritis, patients with neutropenia and splenomegaly should pay attention to screening for RF and anti-CCP antibodies, especially the possibility of Felty syndrome when excluding other causes.

    Aslam F once reported a 47-year-old woman with a history of asthma, hypothyroidism and herpes zoster in a BMJ subjournal [4].

    In addition to low-grade fever, fatigue and sore throat for 1 week, the patient also had new-onset swelling and pain in the hand, foot and shoulder joints with morning stiffness (up to 60 minutes).

    Preliminary examination revealed a reduction in pan blood cells and an elevated level of C-reactive protein, and the doctor considered pharyngitis.

    After the patient was treated with antibiotics, the patient developed dizziness, joint pain, and threatened syncope.

    Further laboratory examinations showed pancytopenia (neutrophil count 0.
    14×109/L) and strong positive anti-CCP antibody, but RF, anti-nuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibody, anti-Chinese Sexual granulocyte cytoplasmic antibodies (ANCA) were all negative.

    Abdominal ultrasound revealed splenomegaly (19 cm), and X-ray examination of the hands and feet did not reveal invasive arthritis.

    It can be seen that this is a case of Felty syndrome with neutropenia and splenomegaly but without RA arthritis.

    Differential diagnosis of Felty syndrome Felty syndrome needs to be differentiated from various diseases that cause splenomegaly with neutropenia, including pseudo Felty syndrome, Hodgkin's lymphoma, and non-Hodgkin's lymphoma.

    Pseudo Felty's syndrome (Pseudo Felty's syndrome) is the most important differential diagnosis of Felty syndrome, also known as large granular lymphocyte (LGL) leukemia.

    The prevalence of false Felty syndrome is less than 1%.

    Both Felty syndrome and pseudo-Felty syndrome can be found in RA, and both have many common clinical features and manifestations, including splenomegaly and neutropenia.

    The main difference between these two syndromes is that patients with pseudo-Felty syndrome have monoclonal large-granular lymphocyte expansion, which is usually derived from T cells expressing CD3, CD8, CD57 and/or CD16 [6].

    Treatment of Felty syndrome The focus of the treatment of Felty syndrome is to control RA.
    Oral low-dose methotrexate is regarded as the first-line treatment, which is beneficial to increase the neutrophil count and prevent the recurrence of infection.

    Therapeutic drugs also include other disease-improving anti-rheumatic drugs (DMARDs), biological agents, etc.

    On the other hand, patients with neutropenia should undergo a comprehensive examination to look for signs of infection.

    Neutropenia without evidence of infection is not an indication for treatment.

    For patients who develop infections, broad-spectrum antibiotics should be used.

    Patients with chronic neutropenia can be treated with G-CSF.

    The treatment goal is to restore the neutrophil count to more than 2×109/L [1].

    Splenectomy was once an important surgical method for the treatment of Felty syndrome.
    At present, its application indications are relatively limited.
    It is mainly suitable for patients with neutropenia and recurrence of severe infections who have failed to treat DMARDs, biologics, G-CSF and other drugs.
    Or patients who require repeated blood transfusions due to severe anemia or severe bleeding due to thrombocytopenia.

    In summary, Felty syndrome is a serious complication of RA, which is more common in middle-aged and elderly women.

    Felty syndrome usually occurs in long-term (more than 10 years of disease), severe, aggressive, and seropositive RA, but its onset may be earlier than the diagnosis of RA.

    Neutropenia is a hallmark feature of Felty syndrome.
    Patients often have skin and respiratory tract infections.
    The overall mortality rate is high and the prognosis is poor.

    However, the syndrome may not cause symptoms.

    Therefore, for patients with neutropenia and splenomegaly, even if there is no history of RA or symptoms or signs of arthritis, the possibility of Felty syndrome should be considered.

    Reference: [1]Patel R,Akhondi H.
    Felty Syndrome.
    [Updated 2020 Jul 6].
    In:StatPearls[Internet].
    Treasure Island(FL):StatPearls Publishing;2021 Jan-.
    [2]Owlia MB,Newman K ,Akhtari M.
    Felty's Syndrome,Insights and Updates.
    Open Rheumatol J.
    2014 Dec 31;8:129-36.
    doi:10.
    2174/1874312901408010129.
    PMID:25614773;PMCID:PMC4296472.
    [3]Turesson C,Schaid DJ,Weyand CM ,et al.
    The impact of HLA-DRB1 genes on extra-articular disease manifestations in rheumatoid arthritis.
    Arthritis Res Ther.
    2005;7(6):R1386-R1393.
    doi:10.
    1186/ar1837[4]Aslam F,Cheema RS, Feinstein M,Chang-Miller A.
    Neutropaenia and splenomegaly without arthritis:think rheumatoid arthritis.
    BMJ Case Rep.
    2018;2018:bcr2018225359.
    Published 2018 Jul 11.
    doi:10.
    1136/bcr-2018-225359[5]Armstrong RD,Fernandes L , Gibson T, Kauffmann EA.
    Felty's syndrome presenting without arthritis.
    Br Med J(Clin Res Ed).
    1983;287(6405):1620.
    doi:10.
    1136/bmj.
    287.
    6405.
    1620[6]Verhoeven F,Guillot X,Prati C,Wendling D.
    Treatment of pseudo Felty's syndrome:Is there a place for rituximab?.
    Joint Bone Spine.
    2015;82(3):196 -199.
    doi:10.
    1016/j.
    jbspin.
    2014.
    12.
    00
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