Chemistry, toxicology & urinalysis
Serology
Rheumatoid arthritis
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PubMed Search: Rheumatoid arthritis
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Diagrams / tables | Pathophysiology | Clinical features | Test indications | Laboratory | Interpretation | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Chen L, Shi J, Li JS. Rheumatoid arthritis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/chemistryrheumatoidarthritis.html. Accessed December 24th, 2024.
Definition / general
- Rheumatoid arthritis (RA), classified as an autoimmune disease, is a chronic inflammatory condition characterized by joint swelling and tenderness, along with the progressive erosion of synovial joints; these symptoms often lead to significant disability and an increased risk of premature mortality (Ann Rheum Dis 2010;69:1580)
Essential features
- Classic presentation of RA includes symmetrical joint pain and swelling, specifically in the small joints of the hands and feet
- Rheumatoid factor (RF) and anticitrullinated protein / peptide antibodies (ACPA / anti-CCP) are key serological markers used in diagnosis, which are highly specific to RA (Ann Rheum Dis 2010;69:1580)
- Pathogenesis of RA involves a complex network of various cytokines, including tumor necrosis factor (TNF), IL1, IL6 and other inflammatory factors
- Early radiographic features include soft tissue swelling and osteopenia near the joints (periarticular osteopenia), while advanced disease is characterized by joint space narrowing, erosions and deformities (Radiology 2008;248:378)
Terminology
- Rheumatoid arthritis
ICD coding
Diagrams / tables
Pathophysiology
- RA is an autoimmune disease where the immune system attacks the synovial tissues in joints, causing inflammation; in this response, T cells, B cells, macrophages and dendritic cells work together to stimulate the production of a variety of cytokines (Biomed J 2021;44:172)
- Cytokines such as tumor necrosis factor (TNF), IL1, IL6, IL17 and granulocyte macrophage colony stimulating factor (GM CSF) recruit and activate inflammatory cells into the joint space
- Autoantibodies form immune complexes that are deposited in synovium and contribute to chronic inflammation (Arthritis Rheum 2000;43:155, Semin Immunopathol 2017;39:437, Autoimmun Rev 2010;9:140)
- Rheumatoid factor is an antibody against the Fc region of immunoglobulin G
- Anticitrullinated protein / peptide antibodies (ACPA), which include anti-cyclic citrullinated peptide (anti-CCP), are antibodies against citrullinated protein or peptides (protein in which arginine amino acid is converted into citrulline amino acid)
- Synovial membrane becomes hyperplastic, known as pannus, which aggressively erodes adjacent cartilage and bone, causing the characteristic erosions seen in radiographic images (Radiology 2008;248:378)
- Some genetic markers, such as the human leukocyte antigen (HLA) DR4, are associated with a higher risk of RA; smoking, obesity and hormonal changes may also induce or exacerbate the disease (Front Med (Lausanne) 2021;8:689698)
Clinical features
- As of 2020, an estimated 17.6 million individuals worldwide were affected, with a higher prevalence observed among women; projections suggest that the global population living with RA will increase to 31.7 million by the year 2050, indicating a rising trend in prevalence (Lancet Rheumatol 2023;5:e594)
- Main symptoms are joint pain and swelling, including the metacarpophalangeal, metatarsophalangeal and proximal interphalangeal joints (JAMA 2018;320:1360)
- Primary clinical feature compared to other types of arthritis is morning stiffness around the joints lasting more than an hour and persistent for at least 6 weeks (J Rheumatol 1999;26:1052)
- Fusiform swelling may occur around the finger joints, which is almost soft because of synovitis and effusion
- Usually, symmetrical joint involvement includes both small and large joints, while the distal interphalangeal joints are rarely affected (Clin Anat 2018;31:216)
- Poorly managed RA can lead to complications beyond the joints, including rheumatoid nodules and rheumatoid vasculitis; it can affect the whole body and involve organs such as the heart and lungs (see Diagrams / tables) (Autoimmun Rev 2021;20:102735, Medicine 2018;46:211)
- Although the etiology has not been identified, genetic factors play an important role, making family members of RA patients at higher risk (Semin Immunopathol 2017;39:395)
Test indications
- In general, assessment of RA is indicated for clinical symptoms with
- Symmetrical joint pain and swelling, particularly in the small joints of the hands, wrists, feet and ankles
- Morning stiffness that lasts longer than 1 hour
- Unexplained joint symptoms persisting for more than 6 weeks
- Family history of RA or other autoimmune disorders
- 2010 RA classification criteria may help physicians establish a diagnosis (see Diagrams / tables) (Ann Rheum Dis 2010;69:1580)
- After an initial evaluation, imaging tests are recommended to evaluate the progression of joint damage, including Xrays, magnetic resonance imaging (MRI) or ultrasound
- In cases with atypical presentation or differentiating from other types of arthritis, HLA typing is recommended for patients (Arthritis Rheum 1997;40:341)
Laboratory
- While testing for RF is primarily employed for the diagnosis and prognosis of RA, it is not exclusive to RA and may also occur in other systemic autoimmune rheumatic diseases and nonrheumatic conditions, including infectious diseases (Arch Intern Med 1992;152:2417)
- Anti-CCP testing is another biomarker included in the 2010 RA classification criteria; a systematic review and meta analysis reported that anti-CCP antibodies have a high specificity (around 96%), which is superior to RF (Can Fam Physician 2016;62:234, Arthritis Res 2002;4:87)
- Patients treated effectively, especially when treated early with antirheumatic drugs, may exhibit a decrease in anti-CCP concentrations (J Rheumatol 2008;35:1903)
- Anti-CCP can be detected in early disease and several years before onset (Front Immunol 2021;12:685312)
- Positive anti-CCP and negative RF may reflect early RA or increased risk of RA development in the near future
- Anti-CCPs have also been reported in other diseases, such as systemic lupus erythematosus (SLE) and tuberculosis (Lupus 2009;18:713, Arthritis Rheum 2008;58:1576)
- Antimutated citrullinated vimentin (anti-MCV) recognizes a naturally occurring isoform of citrullinated vimentin in RA patients (Ann Rheum Dis 2010;69:337, Autoimmun Rev 2010;9:140)
- It has shown that anti-MCV antibody testing yields results similar to those of anti-CCP antibody testing (Ann Rheum Dis 2010;69:337)
- However, anti-MCV is not part of the 2010 RA classification criteria
- It is important to note that inflammatory markers like C reactive protein have been observed to be elevated in pre-RA; however, their utility in enhancing prediction models has not been consistently demonstrated (Arthritis Rheum 2010;62:3161, Ann Rheum Dis 2015;74:1659)
- Although abnormalities in cytokines and chemokines have shown promise in prediction when considered alongside autoantibodies, extensive validation of this approach is still lacking (Arthritis Rheum 2010;62:3161)
Interpretation
Board review style question #1
Which is the primary clinical feature of rheumatoid arthritis (RA) compared to other types of arthritis?
- Asymmetric joint involvement
- Dactylitis (or sausage digits)
- Morning stiffness lasting more than 1 hour
- Pain in the proximal joints of the extremities
- Presence of serum uric acid
Board review style answer #1
C. Morning stiffness lasting more than 1 hour. Morning stiffness that lasts more than 1 hour is a primary clinical feature of RA and helps differentiate it from other types of arthritis, such as ankylosing spondylitis, gout and osteoarthritis. Answer A is incorrect because asymmetric joint involvement is more typical in spondyloarthritis (Best Pract Res Clin Rheumatol 2006;20:401). Answer D is incorrect because pain in the proximal joints of the extremities is more typical in polymyalgia rheumatica (J Intern Med 2022;292:717). Answer E is incorrect because the presence of serum uric acid is more typical in gout (J Clin Rheumatol 2009;15:3). Answer B is incorrect because dactylitis is more typical in psoriatic arthritis (Nat Rev Rheumatol 2019;15:113).
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Board review style question #2
Which of the following analyte(s) is / are highly specific and recommended for diagnosing rheumatoid arthritis (RA)?
- Antinuclear antibodies (ANA)
- C reactive protein (CRP)
- Erythrocyte sedimentation rate (ESR)
- Rheumatoid factor (RF) or anticyclic citrullinated peptide (anti-CCP) antibodies
Board review style answer #2
D. Rheumatoid factor (RF) or anticyclic citrullinated peptide (anti-CCP) antibodies. RF and anti-CCP antibodies are highly clinically specific for RA and are utilized for distinguishing RA from other types of inflammatory arthritis. Answers B and C are incorrect because CRP and ESR are general markers of inflammation and not specific to RA (Allergol Immunopathol (Madr) 2015;43:81); therefore, an abnormally high CRP or ESR counts as 1 point only, according to the 2010 RA classification criteria. Answer A is incorrect because ANA is a diagnostic criteria for systemic lupus erythematosus.
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