Inflammatory Joint Disease – Rheumatoid Arthritis Rheumatoid Arthritis • Most damage to joints occurs within first 2 years • Life expectancy shortens 10 years for women, 4 years for men • Quality of life considerably lower: third of patients stop work within 5 years of diagnosis • F:M 3:1, >45yrs mostly Diagnosis • Difficult to detect in early stages o Morning stiffness >1hr o Weakness, fatigue o Bilateral, symmetric arthritis o ESR, CRP both elevated o Rheumatoid factor, CCP antibodies • Easier to diagnose in established disease o Typical deformities o Erosions on x-ray o Nodules American College of Rheumatology Criteria for RA • Morning stiffness > 1 hour • Soft tissue swelling > 3 joints • Swelling of hand joints (PIP, MCP, wrist) • Symmetrical soft tissue swelling • Subcutaneous nodules • Serum rheumatoid factor (anti-CCP antibodies) • Erosions or periarticular osteopaenia in hand or wrist joints on x-ray o 1-4 for greater than 6 weeks continuous Articular Manifestations • Small joints: o PIP, MCP, wrist, MTP o Hot, swollen, tender deformity • Progressive large joint involvement o MTP tenderness especially 4th and 5th digit Extra-Articular RA • Chronic inflammation: fever, weight loss, anaemia • Disease complications: nerve entrapment e.g. median, atherosclerosis, infection • Treatment complications: osteoporosis, infection, GI bleeding • Vasculitis and serositis o Pleurisy, effusion, pericarditis o Vasculitis of both small and large vessels o Rheumatoid nodules o Felty’s syndrome: RA, neutropaenia, splenomegaly o Interstitial lung disease: 8x risk o Sjogren’s Acute Phase Reaction/IL-6 • Derived from macrophages, endothelial cells, fibroblasts o Hepatic acute phase reaction  ↑CRP, ↑Fibrinogen (↑ESR), ↑TIMP (tissue inhibitors of metalloproteinases), ↓transferrin, ↓albumin (these are decreased because the liver is using the amino acids to make CRP and fibrinogen)  ↑Hepcidin, prevents Fe transport and release  functional Fe deficiency anaemia of chronic inflammation o ↑Platelets o Affects hypothalamus-pituitary-adrenal axis o Stimulates B cell development, IgM/IgG RhF, anti-CP antibodies o Stimulates generations of Th17 proinflammatory lymphocytes Lab Features of RA • No specific test • Rheumatoid factor o IgM against Fc portion of IgG o >5% increase in 70% of RA patients o Product of antigenic stimulation: sepsis, malaria, Tb • Acute phase reactant: ESR, CRP Causes of RA • Genetics o 10x risk if primary relative has it o HLA genetics ~30% (HLA-DR4 (0401, 0404), DR1) o PTPN22: protein tyrosine phosphatase non-receptors  ↑Tyrosine phosphatase activity, ↓T-cell signally with autoreactive T cells escaping deletion  autoimmune diathesis o PADI (peptidylarginine deiminase)  Converts arginine to citrulline  Novel antigenic amino-acid, anti-CCP antibodies highly specific for RA • Smoking o 2-4x, 20% of RA attributed to smoking • Oestrogen o Protective effect o ↑Risk post menopause, ↓HRT o ↑Post partum (↓oestrogen, ↑prolactin) • Omega-3/6 balance • Periodontitis o Porphyromonas gingivalis: expressed PADI Anti-CCP Antibodies: citrullinated peptides • As sensitive as IgM RhF (65%) but more specific (97%) • Rare in healthy normal: 2% OA, 7% CTD • Present in 35% of RhF-Neg RA patients • Adverse prognostic factor