Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology that is characterised by its pattern of diarthrodial joint involvement. Its primary site of pathology is the synovium of the joints - the synovium becomes inflamed and proliferate, forming panus, which invade bone, cartilage and ligament, leading to damage and deformities. In some cases, chronic destruction can lead to joint fusion. RA may also affect extra-articular areas - lesions may involve skin, heart, blood vessels and lungs, leading to clinical manifestations that overlap with other autoimmune disorders

Etiology

Genetic predisposition and environmental factors contribute to the development, progression, and persistence of disease. Susceptible HLA genes, alongside environmental factors, will lead to lymphocyte activation and enzymatic modification of self-protein.

It is estimated that 50% of the risk of the development of RA is related to inherited genetic susceptibility. Over 90% of patients have one of the susceptible HLA antigens. RA is definitely associated with HLA-DR4 and, to a lesser extent, HLA-DR1 positivity. HLA-DR4 allele is associated with ACPA-positive RA. Evidence suggests that an epitope () on a citrullinated protein, cincullin, mimics an epitope on many microbes and can be presented as a class II HLA-DR4 molecule. However, HLA-DR4 positivity also occurs in 20-30% of the general population, and therefore genetics does not completely explain the pathogenesis of RA.

Environmental factors that promote autoimmunity are involved but has not been clearly defined: infection and smoking may promote citrullination of self-proteins, creating new epitopes that trigger autoantibody production.

Epidemiology

• Affects all races worldwide

  • Prevalence is low in black African and chinese people

• Females > males with a preponderance of 3:1

• Peak age 35-45 years

  • It can present from early childhood, where it is rare, to late old age

• Occurs in about 1% of the adults in the US; prevalence increases with age

Pathophysiology

History and Presentation

RA usually have a subacute (20%) or insidious (70%) onset with arthritic symptoms of pain, swelling, and stiffness, with the number of joints involved increasing over weeks to months. About 10% of patients have an acutely severe onset that can occur over a few days or explosively overnight, and a few start with episodic symptoms that progress to persistent disease. The episodic pattern of symptoms is defined as palindromic rheumatism - not all patients with palindromic rheumatism develop RA, and they respond to hydroxychloroquine, supporting the idea that palindromic rheumatism is a distinct phenotype of RA. It presents as a progressive, symmetrical, peripheral polyarthritis. 10% of patients present with a monoarthritis picture of the knee or shoulder with carpal tunnel syndrome.

Most commonly affected joints in RA

The joints most commonly involved first are the MCPs, PIPs, and MTps. Larger joints generally become symptomatic after small joints. Patients may start out with only a few joints involved (oligoarticular onset) but progress to the involvement of multiple joints (polyarticular) in symmetric distribution within a few weeks to months. Involvement of the thoracolumbar, sacroiliac, or hand distal interphalangeal (DIP) joints is very rare in RA and should suggest another diagnosis, such as a seronegative spondyloarthropathy (sacroiliac joints), psoriatic arthritis (DIP joints), or osteoarthritis (lumbar spine, DIP joints).

Due to the mechanism of RA affecting the synovial space, joints which lack this tend not be involved; axial joints tend to be limited to the cervical spine, particularly C1/C2, as there are synovial joints here. The lumbar spine is not involved.

To have a symmetrical involvement of joints means to both have a bilateral involvement (each side of the body) and the whole joint affected, as compared to osteoarthritis which usually only involve the weight-bearing areas of the joint.

On examination, the affected joint will be painful is pressure is applied to the joint or on movement with/without joint swelling. Synovial thickening with a boggy feel on palpation will be noted. Joint erythema and warmth are usually absent, and wrist involvement may present with typical signs and symptoms of carpal tunnel syndrome. With multiple joint involvement, reduced grip strength will be seen on physical testing.

Classical physical findings in severe disease

• Ulnar deviation

• Metacarpophalangeal joint subluxation

• Swan neck deformity

• Boutonniere deformity

• Bowstring sign

Other findings in late stages of RA include reduced range of motion in the shoulders, elbows and knees. In the feet, hallux valgus is common, as well as other toe deformities.

Rheumatoid nodules are the most common extra articular manifestation of RA - commonly found on pressure points such as the olecranon but may also occur over the joints of the hands and feet, the patellar, and the Achilles tendon.

Interstitial lung disease (ILD) affects 5 to 16% of patients with RA and is associated with RA specific autoantibodies and increased mortality - some patients may present with ILD before developing joint inflammation with positive RF and ACPA. RA-associated ILD is associated with ACPA, anti-carbamylated protein antibodies (anti-CarP) and anti-malondialdehyde-acetaldehyde antibodies (anti-MAA).

Ophthalmological manifestations include secondary Sjogren syndrome with dry eyes and dry mouth. Inflammatory eye disease such as episcleritis and scleritis have become uncommon with new therapies for RA. Similarly, Felty syndrome, which is the combination of long-standing seropositive RA (RF and ANA), leukopenia and splenomegaly, is rarely seen today. These patients may have chronic non-healing ulcers and an increased risk of bacterial infection. Vasculitis involving both medium and small-sized blood vessels can also be seen as a presenting symptom of RA. Patients with rheumatoid vasculitis may exhibit mononeuritis multiplex or asymmetric polyneuropathy.

Investigations and diagnosis