Monday: Rheumatoid Arthritis Flashcards
Rheumatoid arthritis? What is it associated with?
Symmetrical; rheumatoid factor, systemic inflammation.
Disease of joints and systemic disorder that can affect skin, blood vessels, heart, eyes, pleura, lungs, peripheral nerves, exocrine glands.
RA affects what percent of adult population? Females to males?
1%
3:1 females to males
Peak incidence between 4th and 6th decade. Course of illness is variable.
Pathogenesis of RA?
Certain alleles inherited at HLA 1 locus (encodes chain of HLA DR class II major histocompatibility (MHC) molecule.
Sequence of amino acids at residues 67-74. Determines disease susceptibility and severity of disease. Critical peptide binding region of HLA-DR: T cell recognition of antigens is key to pathogenesis of RA. Failure to bind important antigenic peptides or cause binding of inappropriate peptides leading to autoimmunity/inflammatoin.
How do T cells and macrophages play a role in pathogenesis of RA?
Lymphocytes seen in chronically inflamed rheumatoid synovial membrane=T cells.
Cytokines produced by macrophages are prominent in RA synovial fluid (IL1, IL6, TNFalpha) and tissue and inhibition of TNF alpha with monoclonal antibodies appears to reduce RA activity.
How are B lymphocytes involved in RA?
70% of RA patients produce rheumatoid factor (an auto-antibody directed against constant region of IgG).
IgG rheumatoid factor is believed to deposit in arterial lumina to cause vasculitis in some patients.
Is rheumatoid factor specific to RA?
No. It can be found in low levels in normal people and rises in presence of chronic inflammation (endocarditis, osteomyelitis, parasitic infestations).
RA: Pathology
Synovial membrane infiltrated by macrophages, lymphocytes, plasma cells, granulocytes.
Germinal centesr seen occasionally.
Rheumatoid nodule with fibrinoid center, palisades of epithelioid cells, and mantle of lymphocytes distinguishes RA from other arthritidies.
Severe disease: RA
Synovial membrane=gross hypertrophy and may erode articular cartilage and bone.
Erosions may be due to lysosomal hydrolases released by granulocytes and macrophages or to influence of cytokines on cells within the bone or cartilage. Progressive bone/cartilage damage and chronic swelling reduces ability of joints to withstand stresses of normal use.
Long-standing RA=loss of cartilage, joint deformation, and fibrous/bony ankylosis.
What happens to tendons in RA?
Tendons become weakened or displaced causing imbalance of forces that maintain alignment of complex joint systems such as those in the hand (leading to malalignment and subluxation). Outright tendon rupture can occur.
Symmetrical polyarthralgias, morning stiffness, fatigue=?
Early symptoms of RA
RA involves which joints? Where in particular?
Any synovial joint.
Wrists and hands especially.
Ulnar deviation, swan-neck, boutonniere deformities of fingers comes from what pathologic process in RA?
Long-standing joint and tendon inflammation.
What are other organs affected by rheumatoid inflammatory process?
Heart (pericarditis, cardiomyopathy, valvular incompetence by nodules; intersitital fibrosis).
Eyes (scleritis, scleromalacia preforans)
Nervous system (mononeuritis multiplex and peripheral compression syndromes like median neuropathy).
Kidneys (amyloid deposition)
Hematopoietic system (anemia, Felty syndrome, splenomegaly, leukopenia)
Vasculitis can cause skin lesions, leg ulcers, necrotizing arteritis of viscera, digital infarctions, fever.
Patients at greater risk of development of lymphoid malignancies.
What is Sjogren syndrome?
15% of RA patients.
Due to infiltration of exocrine glands with lymphocytes.
Which lab markers should help you diagnose RA?
Rheumatoid factor (RF)
CCP (cyclic citrullinated peptide)=May be more specific marker for RA than RF.
Active RA is frequently but not always accompanied by elevated erythrocyte sedimentation rate.
Most patients have normochromic, normocytic anemia. Some have antinuclear Ab (low titer)
Joint fluid has lots of PMN leukocytes, increased protein, decreased viscosity and complement.
Radiographic changes of RA?
Early changes in soft tissues (fusiform swelling and joint effusion).
Osteopenia is more generalized as disease progresses.
Cartilage destruction produces narrowing of joint. Erosion of bone in metaphyseal region under collateral ligament attachments.
End-stage: Malalignment, displacement, and ankylosis of joint.
MRI may be more sensitive marker of early bone erosion.
RA criteria for diagnosis?
Four of 7 criteria (Criteria 1-4 must be present for 6 weeks):
- Morning stiffness lasting greater than one hour.
- Arthritis of three or more joint areas simulatenaously
- Arthritis of hand joints (at least one swollen wrist, MCP, or PIP)
- Symmetric arthritis
- Subcutaneous nodules observed by physician
- Serum rheumatoid factor
- Typical radiographic changes (unequivocal periarticular osteopenia or erosions)
Treatment of RA (Pain-relief):
Salicylates (but some patients can’t tolerate high doses)
NSAIDS esp. selective COX2 Inhibitors. These are just anti-inflammatory and do not alter progression of disease.
Drugs that modify RA disease:
Methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide.
Other agents: gold, azathiorpine, cyclosporine, cyclophosphamide. These have serious side effects.
TNF inhibitors: Etanercept, Infliximab, and Adalimumab.
Recominant IL1 receptor antagonist (Anakinra).
Targeted B cell therapy with Rituximab.
Describe use of corticosteroids in treatment of RA?
Corticosteroids can be used to alleviate intractable joint inflammation or vasculitis in RA.
Use of steroids should be minimized to limit toxicity.
Low dose systemic corticosteriods (prednisone) should be used until DMARD reaches therapeutic levels (three months).
Side effects of long term steroids: Calcium and vitamin D intake. Weight bearing exercise to avoid osteoporosis.
Why are repeated injections bad?
They may increase risk of articular cartilage damage from catabolic effects of local steroids.
What is most common surgery in RA patients?
Arthroplasty
Spondyloarthropathies and chronic seronegative arthritides are whic diseases?
Ankylosing spondylitis, reactive arthritis (Reiter’s syndrome) and spondylitis associated with psoriasis and IBD (spondyloarthropathies).
Associated with inflammation of axial skeleton, absence of RF, tendency of inflamed areas to heal with fibroblastic proliferation followed by new bone formation.
Most Caucasian patients with ankylosing spondylitis express HLA-B27 allele. Prevalence of allele is variable in other diseases and racial groups.
What is pathogenesis of reactive arthritis?
Aberrant host response to pathogenic microoragnism.
Ankylosing spondylitis affects what age group and gender?
Young to middle-aged people (mostly men)
Ankylosing spondylitis: Presentation
Insidious onset of pain and stiffness in lower back and gradual loss of spinal mobility.
Inflammatory arthritis of large joints such as hip occurs. Illness may cause inflammation in uveal tract of eye and intima of aorta.
Tendency to progress slowly up the spine resulting in diminished mobility and fusion of spine and sacroiliac joints.
Reactive arthritis facts
Arthritis of large joints (knees and ankles), uveitis, skin lesions, and urethritis.
Linked to infection with chlamydia in US.
Other parts of world: Diarrhea instead of urethritis and shigella, yersinia, salmonella are causes.
Tendency toward exuberant periostitis in heel. One episode of illness for some but many have multiple attacks.
Psoriatic arthritis: facts
Small percentage of patients with psoriasis develop arthritis.
Usually asymmetrical oligoarthritis. Occasionally quite destructive.
Some patients have symmetric inflammatory arthritis involving DISTAL interphalangeal joints.
Other small group has spondylitis that doesn’t differ much from ankylosing spondylitis. Associated with HLA-B27 allele.
Activity of skin lesions doesn’t correlate with peripheral arthritis.
Arthritis related to IBD: facts
Associated with peripheral arthritis which reflects activity of bowel disease and associated with erythema nodosum.
Some patients develop sacroiliitis and spondylitis whose activity is independent of bowel disease.
Many patients are HLA-B27 positive.
