rheumatoid arthritis Flashcards
epidemiology, genetics, natural history, clinical expression including clinical subtypes, pathology, and disease pathogenesis.
What are some poor prognostic signs in rheumatoid arthritis?
Rapid development of functional disability, weight loss, subcutaneous nodules, positive rheumatoid factor, and progressive erosive changes on x-ray are poor prognostic signs.
Anti-CCP antibodies predicts higher mortality in those without DMARD treatment. PMID: 24574208[uid]
What should the initial H and P include to support a diagnosis of rheumatoid arthritis?
Onset (month/year), duration (month, year) and site of joint symptoms (small/large joints), and presence or absence of definite swelling/tenderness in the hands and feet (site and severity of small joint involvement). Other sites mentioned if positive. Subcutaneous nodules are pathognomonic.
Helpful negative findings should include abdominal exam(exclude IBD), skin exam (exclude psoriasis, and systemic lupus).
What laboratory testing is most helpful in diagnosing rheumatoid arthritis?
Helpfulness of initial laboratory testing depends on the prior probability. In likely cases of rheumatoid disease, rheumatoid factor, anti-cyclic citrullinated peptide antibody (anti-CCP) help to confirm the diagnosis. ANA, testing for hepatitis C are usually done to exclude alternatives. In unlikely cases, CBC, acute phase reactants helpful to exclude inflammatory arthritis when osteoarthritis or fibromyalgia seems more likely.
X-rays usually do not show specific changes for months to years after disease onset but are helpful to establish a baseline.
What is the role of MRI and ultrasound in the diagnosis of rheumatoid arthritis?
MRI and ultrasound evaluation of peripheral joints usually does not add diagnostic information beyond that obtained from physical examination. Joint tenderness is more helpful than equivocal findings on imaging studies.
Either modality helps to evaluate a possible ruptured popliteal cyst.
What diagnostic changes are present initially in the synovial fluid in rheumatoid arthritis?
None.
Synovial fluid analysis helps to establish the presence of definite inflammation/arthritis and exclude infection and crystalline arthritis.
Rheumatoid factor is almost never present in the synovial fluid when absent in the peripheral blood.
What are the 2010 criteria for diagnosis of rheumatoid arthritis.
The 2010 ACR/EULAR criteria require 6 of possible 10 points, from 4 domains.
domain 1: joint number and site:
>10 including 1 small: 5 pts
4-10 small joints: 3 pts
1-3 small (mcp pip, 2-5 mtp, thumb,wrists): 2 pts
1-10 large jts(shoulders, hips, knees, ankles): 1 pt
Domain 2: RF or anti CCP
low positive 2 pts
high positive(>3xUL) 3 pts
Domain 3: acute phase reactants
ESR or CRP 1 pt
Domain 4:
symptoms>6 wks, 1 pt
The number of points per domain indicate the degree to which such findings predict rheumatoid disease course instead of disappearing or morphing into SLE, scleroderma, or spondyloarthropathy.
What other diseases tend to occur in patients with rheumatoid arthritis.
Patients with rheumatoid arthritis experience more problems than controls with infections, cardiovascular disease, and lymphoma.
The risk for premature cardiovascular disease in smokers with anti CCP antibodies, and 2 copies of the shared epitope is 7.8 . Over 10 yrs of RA, other extraarticular features, and positive anti CCP constitutes indication for a statin.
What factors predict excessive mortality in rheumatoid arthritis.
Life expectancy in rheumatoid arthritis is reduced especially if there is polyarticular disease, extraarticular disease, persistently elevated esr/crp, high titer rheumatoid factor, bialleic shared epitope (HLA-DR link).
Does dip joint involvement occur in rheumatoid arthritis?
Dip joint involvement in rheumatoid arthritis does occur but most often along with pip and mcp inflammation. Isolated dip joint arthritis is much more common in osteoarthritis, and psoriatic arthritis.
What underlies the HLA association with rheumatoid arthritis?
The HLA DRB1 gene with the shared epitope at amino acid location 67-74.
The shared epitope includes 4/20 known alleles with 2 showing strong relative risk (5-14). The amino acid sequences making up the shared epitope include QKRAA, QRRAA, or RRRAA. Q=glutamine K= lysine R=arginine A=alanine
If the shared epitope is homozygous, the relative risk can reach 49 !
What features of rheumatoid arthritis predict low bone density?
Age, disease activity, loss of height, prednisone over 10 mg daily, and low muscle mass predict osteoporosis. Stress fractures of the fibula and vertebral compression fractures are more common in osteoporosis associated with rheumatoid arthritis.
What is the relationship of prednisone dosage to steroid myopathy?
Steroid myopathy generally requires 40 to 60 mg daily for over one month, and improves within 3 to 4 weeks after dosage reduction. Steroid myopathy usually presents with improvement of synovitis and painless weakness.
When is an elevated sedimentation rate helpful in the assessment of generalized joint pain ?
An elevated sedimentation rate is useful to identify mild synovitis, and exclude fibromyalgia as the sole cause of joint pain. Obese diabetics, often have minor elevation in sedimentation rate along with typical fibromyalgia.
Is rheumatoid arthritis a risk factor for excess cardiac mortality?
Atherosclerotic coronary artery disease has a standardized mortality ratio of 1.5, and atrial fibrillation (8.2 vs 6 events/1000 pt-yr). Both are significant.
Pericarditis/tamponade, amyloidosis, myocarditis are increased but too rare to affect overall mortality.
How does lymphoma risk in rheumatoid arthritis vary with the disease severity and treatment?
Lymphoma risk increases markedly with disease activity (up to 9x) whereas relative risk with drug treatment is 1.2 for methotrexate, 1.4 for azathioprine, and 2.2 for cyclophosphamide.
Are serious infections more frequent in rheumatoid arthritis?
Relative risk of infection severe enough to require hospital admission is 1.8. Excess risk is related to immune suppression mediated by the disease or its treatment, cigarette smoking, subclinical lung disease, and musculoskeletal immobility.
Glucocorticoids increase infection rates-dose related, DMARD treatment decreases them.
What factors affect employment in rheumatoid arthritis?
Employment is decreased if there is joint pain, impaired physical function, lack of at least an ACR 20% response to treatment, and a difficult commute. Employment is increased if self-employed, positive attitude, at least an ACR 20% response to treatment, and workplace ergonomic improvements.
Is life expectancy decreased In patients with rheumatoid arthritis?
Studies in pre anti-TNF era show a mortality risk (SMR) higher for women 1.5 than men 1.1, worse if severe disease, rheumatoid factor (especially anti-CCP) positive, and less in people who respond to treatment-0.4 if due to methotrexate.
What is the best way to asses rheumatoid disease control over the years?
Plain films of the hands and feet every 2 years is the most quantitative way to judge progressive joint damage. New erosions, periarticular osteoporosis, and joint space narrowing indicate need for additional treatment.
Increasing treatment based on progressive damage improves disease control better than clinical and laboratory features alone.
What is the role of rest and exercise the management of rheumatoid arthritis?
Exercise, both resistive and endurance have a uniformly positive effect especially on self efficacy, and disease control. Rest, for the sake of rest, has shown no positive results in controlled trials.
What are some typical rheumatoid deformities?
Typical rheumatoid deformities that develop over decades, include swan neck hyperextension at pip joints, hyperflexion at dip joints, boutonniere-hyperflexion at pip joints , ulnar drift at MCP joints, wrist subluxation, loss of elbow extension, loss of shoulder rotation, knee flexion contractures, cock up toes, hammar toes,
What is the rate of relapse should one stop methotrexate or anti-TNF therapy in quiescent rheumatoid arthritis?
In one year about 80% relapse compared to 40% should treatment be continued. Stopping Rx results in disease flare earlier for anti-TNF than MTX.
Should a patient insist on a drug holiday, followup every 1-3 months would be appropriate.
What are the adverse reactions to anti-TNF treatment that require stopping therapy?
Severe injection reactions-local or systemic, neutropenia, development of heart failure, psoriasis, malignancy, severe infection, demyelinating disease, autoimmunity.
How does methotrexate reduce rheumatoid inflammation?
Methotrexate increases the extracellular concentration of adenosine which stimulates adenosine receptors (ADORA1-A2A- A2B) and subsequent inhibition of antigen presentation, costimulation, immune cell trafficking and proliferation, cytokine production, and cytotoxicity.
Methotrexate inhibits ATIC (5-Aminoimidazole-4-carboxamide ribonucleotide Transformylase/IMP Cyclohydrolayse) which forms IMP, Increasing AICAR (C9H13N5O4, AICA Ribonucleotide, 5-amidoimidizole-4-carboxamide ribonucleotide) levels -> inhibition AMP deaminase 1 and adenosine deaminase which increases adenosine (C10H13N5O4) levels and extracellular release of adenosine.
Adenosine receptors are 7 transmembrane G protein coupled receptors, affecting cAMP concentration.
What can cause macrocytic anemia during the course of treatment of rheumatoid arthritis?
Macrocytic anemia may be due to folate or b12 deficiency, or drugs that interfere with nucleic acid synthesis, such as methotrexate. Rarely increased reticulocytosis from any cause, myelodysplastic syndrome such as acute leukemia, alcohol abuse, liver disease, or hypothyroidism is present.
