Epidemiology

Etiology

Idiopathic inflammatory autoimmune disorder of unknown etiology
Risk factors include:
- Genetic disposition: associated with HLA-DR4 and HLA-DR1
- Environmental factors (e.g., smoking)
- Hormonal factors (premenopausal women are at the highest risk, suggesting a predisposing role of female sex hormones)

Certain interstitial tissue proteins (e.g. intracellular filament protein vimentin, filaggrin, type II collagen) undergo a posttranslational modification that involves the conversion of arginine to citrulline (citrullination).
Citrullinated proteins are recognized as foreign by the antigen-presenting cells that present them to CD4+ T cells.
Activation of CD4+ T cells leads to the following sequences of events:
- IL-4 production → B-cell proliferation and differentiation → production of anticitrullinated peptide antibodies → type II hypersensitivity reaction and type III hypersensitivity reaction
- Migration of CD4+ T cells to synovial joints → secretion of cytokines (IFN-γ, IL-17) → recruitment of macrophages → secretion of cytokines (TNF-α, IL-1, IL-6) → inflammation and proliferation
Bouts of inflammation, angiogenesis, and proliferation → proliferative granulation tissue with mononuclear inflammatory cells → pannus and synovial hypertrophy → invasion, progressive destruction, and deterioration of cartilage and bone
Antibodies against Fc portion of IgG (rheumatoid factor, RF) are produced to aid in removing autoantibodies and immune complexes.
- RF excess triggers formation of new immune complexes and type III HSR
- Individuals with positive RF are more likely to develop extraarticular manifestations.

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Definition: a potentially life-threatening complication caused by the inflammatory destruction of the ligaments affecting the atlantoaxial joint and the intervertebral joints
Clinical features
- Pain and stiffness of the neck (typically early-morning neck pain at rest)
- Head tilt
- Neurological deficits
  - Cervical radiculopathy with peripheral paresthesias of the upper limb
  - In some cases, symptoms of high spinal cord compression
    - Slowly progressive spastic quadriparesis
    - Hyperreflexia or positive Babinski reflex
    - Respiratory insufficiency
Diagnostics
- Extension and flexion x-rays of the cervical spine
- MRI

Warning

Endotracheal intubation can acutely worsen the subluxation and cause compression of the spinal cord and/or vertebral arteries.

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Anticitrullinated peptide antibodies (ACPA), e.g., anticyclic citrullinated peptide (anti-CCP)
- Tissue inflammation causes arginine residues in proteins such as vimentin to be enzymatically converted into citrulline through a process called citrullination. This alters the shape of the proteins, which can then serve as neoantigens that generate an immune response.
Rheumatoid factor (RF): IgM autoantibodies against the Fc region of IgG antibodies

Parvovirus B19 will presents with similar symptoms, except for rash, normal ESR, and acute onset
See Osteoarthritis > Differential diagnosis

Glucocorticoids
- Systemic prednisone
  - Longer-term therapy: Only use in patients with highly active RA
NSAIDs and selective COX-2 inhibitors: relieve symptoms, but do not improve the prognosis

Methotrexate (MTX): first-line treatment in patients with moderate to high disease activity
- To minimize adverse effects, administer folic acid.

Indication: persistent moderate or severe disease activity after 3 months of conventional DMARD therapy
Agents
- TNF-α inhibitors: e.g., adalimumab, infliximab, etanercept
  - a receptor molecule (cept)