Rheumatoid Arthritis Chapter

Rheumatoid Arthritis (RA)

• RA is a chronic inflammatory autoimmune disease characterized by persistent inflammation that primarily affects peripheral joints, producing a non-suppurative proliferative and inflammatory synovitis.
• It typically starts as an insidious symmetrical arthritis and has an unpredictable and variable course.
• RA often progresses to the destruction of articular cartilage and, in some cases, ankylosis (adhesion) of the joints.
• Extra-articular lesions may occur in the skin, heart, blood vessels, and lungs.
• Articular manifestations include symmetric arthritis, principally affecting the small joints of the hands and feet, with pain and swelling in affected joints aggravated by movement.
• Morning stiffness ≥1 hour is a common symptom.

Pathogenesis of RA

• Genetic predisposition and environmental factors contribute to the development, progression, and chronicity of the disease.
• Pathologic changes are mediated by antibodies against self-antigens and inflammation caused by cytokines, predominantly secreted by CD4+ T cells.
• The inflammation localizes to the joint, recruiting macrophages and triggering activation and/or proliferation of synovial cells, chondrocytes, and fibroblasts.
• The production of proteolytic enzymes and cytokines contributes to the destruction of cartilage and bone.
• CD4+ T helper (TH) cells may initiate the autoimmune response by reacting with an arthritogen.

Morphology of RA

• Grossly, the synovium becomes edematous, thickened, and hyperplastic, transforming its smooth contour to one covered by delicate and bulbous villi.
• Histologic features include synovial cell hyperplasia and proliferation, dense inflammatory infiltrates of CD4+ helper T cells, B cells, plasma cells, dendritic cells, and macrophages, and increased vascularity resulting from angiogenesis.

Juvenile Idiopathic Arthritis (JIA)

• JIA is a heterogeneous group of disorders of unknown cause that present with arthritis before age 16 and persist for at least 6 weeks.
• In contrast to RA, JIA is characterized by oligoarthritis, systemic disease, and large joints being affected more often than small joints.
• Rheumatoid nodules and rheumatoid factor are usually absent, and anti-nuclear antibody (ANA) seropositivity is common.
• The pathogenesis is unknown but similar to adult RA, with risk factors including HLA and PTPN22 variants.
• Damage in JIA appears to be caused by TH1 and TH17 cells and cytokines produced by these and other inflammatory cells.

Seronegative Spondyloarthropathies

• Spondyloarthropathies are a heterogeneous group of disorders that share the following features:
  1. Absence of rheumatoid factor
  2. Pathologic changes in the ligamentous attachments rather than synovium
  3. Involvement of sacroiliac joints, with or without other joints
  4. Association with HLA-B27
  5. Bony proliferation leading to ankylosis (fusion of joints)

Ankylosing Spondylitis

• Ankylosing spondylitis is the prototypical spondyloarthritis, causing destruction of articular cartilage and bony ankylosis, especially of the sacroiliac joints.
• The disease becomes symptomatic in the second and third decades of life as lower back pain and spinal immobility.
• Involvement of peripheral joints, such as the hips, knees, and shoulders, occurs in at least one-third of affected individuals.
• Approximately 90% of patients are HLA-B27 positive.

Reactive Arthritis

• Reactive arthritis is defined by a triad of arthritis, nongonococcal urethritis or cervicitis, and conjunctivitis.
• Most affected individuals are men in their 20s or 30s, and more than 80% are HLA-B27 positive.
• The disease is probably caused by an autoimmune reaction initiated by previous infection of the genitourinary system (Chlamydia) or the gastrointestinal tract (Shigella, Salmonella, Yersinia, Campylobacter).

Infectious Arthritis

• Joints can become infected from hematogenous dissemination, direct inoculation through the skin, or from contiguous spread from a soft tissue abscess or osteomyelitis.
• Infectious arthritis is potentially serious, because it can cause rapid, permanent joint destruction.
• Suppurative arthritis is caused by bacterial infections, usually entering the joints from distant sites by hematogenous spread.
• The main agents include H. influenza, S. aureus, and gonococcus.
• Individuals with sickle cell disease are prone to infection with Salmonella.