Rheumatology: RA Flashcards
RA Dx Criteria
Need at least four of seven criteria:
- Morning stiffness lasting at least 1 hr
- Soft- tissue swelling or fluid in at least 3 joint areas simultaneously
- At least one area swollen in a wrist, MCP, or PIP joint*
- Symmetric arthritis*
- Rheumatoid nodules
- Abnormal amounts of serum rheumatoid factor
- Erosions or bony decalcification on radiographs of the hand and wrist
Stage I
Early
- No destructive changes on radiographs
- May have radiographic evidence of osteoporosis
Stage II
Moderate
- Radiographic evidence of osteoporosis; may have slight subchondral bone or cartilage destruction
- No joint deformities; limitation of joint mobility may be present
- Adjacent muscle atrophy
- Nodules and tenosynovitis may be present
Stage III
Severe
- Radiographic evidence of osteoporosis as well as cartilage and bone destruction
- Joint deformity without ankylosis
- Extensive muscle atrophy
- Nodules and tenosynovitis may be present
Stage IV
Terminal
- Fibrous or bony ankylosis
- Criteria of stage III
Onset of RA
RA can present as:
Abrupt and acute
Gradual and insidious
Subacute between these extremes
A gradual onset is most common (at least 50% of cases)
An abrupt and acute onset is much less common (10–25%).
Presentation of RA
RA usually starts as an articular disease with one or many joints affected.
It can start with an extra-articular or non-articular presentation, such as a local bursitis, tenosynovitis, or carpal tunnel syndrome.
A systemic presentation with diffuse polyarthralgia (joint pain) or polymyalgia (muscle pain) can also happen.
Onset also frequently has a variety of non-specific symptoms such as, generalized weakness, fatigue, anorexia, weight loss or fever
5-10% of people have some episodes then never have it again
Most common: polycyclic progressive where levels of disease activity fluctuate
Areas of Cartilage Destruction
RA does not like the spine aka does not affect usually
End up having cartilage destruction
Hypertrophy because endothelial GF, other GFs which creates chronically swollen inflamed tissue; don’t always see redness
OA vs. RA
Systemic inflammation in RA – C reactive protein go up, ESR goes up; these are usually in range or only slightly elevated in OA
More bony swelling and destruction in RA than OA
Genetic Factors
RA has a multifactorial etiology. With research showing genetic factors account for 60% the risk to develop RA.
Associated with HLA-DR4 and the DR– associated alleles, DRB10401 and DRB10404 and contribute 30–50% of the genetic risk.
The HLA susceptability genes are a called the “shared epitope” theory located on the third hypervariable region of the HLA-DRB1 zone
Possible Trigger of RA
Hormonal and reproductive factors may play a role in the predominance of RA in women.
Parity, breast feeding and the use of exogenous hormones have been implicated in susceptibility to the disease.
Environmental and lifestyle factors include: obesity, dietary exposure to antioxidants, smoking, coffee consumption and certain specific occupational exposures.
There is no conclusive epidemiological evidence for a single infectious trigger
Cellular Processes in RA
Something becomes an Ag and stimulates something to release IFN, IL-6, etc. that go to T helper cells; stimulate T cells and differentiate into different cell lines; RANK L on surface of osteoblasts an osteoclasts
Osteoblasts are stimulated by T cell and lead to erosions in RA, and stimulation from macrophages from autoAb that cause hyperplasia of chondrocytes, VEGF cause vasculature growth and become leaky and macrophage also stimulate adipocytes and increase risk for heart attack and stroke because can cause metabolic syndrome
Adaptive response is stimulated and causes all these things
Hx and Dx of RA
Morning stiffness and symmetrical swelling in the wrists, PIPs and MCPs is the typical history for rheumatoid arthritis.
▪Early diagnosis of RA is critical but many cases of ‘early arthritis’ are not RA.
▪Antibodies to cyclic citrullinated peptide (anti-CCP) occur earlier than rheumatoid factor (RF) and are more specific for RA.
▪Aggressive early administration of disease-modifying antirheumatic drugs (DMARD’s) is critical to a good outcome
Rheumatoid Factor
RF is a series of antibodies that recognize the Fc portion of an Ig molecule as their antigen.
Most measured RFs are IgM RFs.
There are many conditions associated with a +RF therefore a positive test does not make the diagnosis.
However…..having a +RF especially at a significant titer does indicate increased risk for more aggressive disease and extra-articular problems.
Disease activity cannot be monitored by RF levels
False Positive RF
RF occurs in normal healthy people 2-4% until the age of 60 and then goes to 5% until 70 years old then increases to 10-25% after 70.
Chronic hepatic or pulmonary disease; Other rheumatic diseases (SLE, PSS, MCTD, Sjogren’s, Polymyositis or Sarcoid); Malignancy; Infections; Cyroglobulinemia
Anti-CCP
The Anti-CCP assay looks for antibodies against serum anti-cyclic citrullinated peptide antibodies (anti-CCP).
These antibodies if detected have a high specificity and sensitivity for RA.
They can be seen in serum up to 10 years before the onset of RA.
Anti-CCP antibodies have been reported to be an independent and important predictor of joint damage and disease progression.
The current assay has a sensitivity of 78%, specificity 98%.
Anti-CCP – specific for synovial fluid itself and direction T and B cells to the fluid; acts like an antigen but is not an antigen, which then stimulates the whole cascade
Anti-Mutated Citrullinated Vimentin (anti-MCV)
A new antibody screening test for RA developed over the last 2-3 years and available on the market for patient screening now.
It is a highly RA specific antibody 93.2% with sensitivity of 76.9%.
Measures IgG antibodies to mutated citrullinated vimentin (MCV) which are found in inflamed synovium in RA patients.
Also is a predictor of severe outcome in RA patients
Prognosis
70 percent of joint erosions detectable by x-ray of hands and feet occur in the first two years of disease.
At 20 years, over 60 percent of RA patients belong to functional class III (significantly impaired, self-caring, using aids, requiring joint replacements) or class IV (loss of independence, requiring daily care).
Increased evidence of: Infections, Cardiovascular disease and Malignancies.
Life-expectancy of RA less than age-sex matched control populations up to 15 years, especially in patients with: Polyarticular disease, Systemic extra-articular disease, Persistent disease activity (high ESR, CRP), RF and anti-CCP positivity, HLA-DR & chain ‘shared epitope’.
Other Manifestations of RA
General: fever, LAD, weight loss, fatigue.
Dermatologic: palmar erythema, subcutaneous nodules, vasculitis.
Ocular: episcleritis, scleritis, choroid and retinal nodules.
Pulmonary: pleuritis, nodules, interstitial lung disease, bronchiolitis obliterans
Cardiac: pericarditis, myocarditis, coronary vasculitis, nodules on valves.
Neuromuscular: entrapment neuropathy, peripheral neuropathy, mononeuritis multiplex.
Hematologic: Felty’s syndrome, Large granular lymphocytic syndrome, lymphomas.
Other: Sjogren’s syndrome and amyloidosis
Boutonniere and Swan Neck Deformity
PIP flexion and DIP hyperextension for boutonniere deformity
Swan neck deformity- DIP flexion and PIP hyerextension
Cervical Spine Involvement
Occurs in 30-50% of patients and is found at the C1-C2 level.
C1-2 anterior subluxation is atlantoaxial subluxation that can lead to spinal cord compression.
C1-2 vertical subluxation (occurs in 5% of RA patients) can cause herniation and death
Happens in 30-50% of patients with untreated RA
For RA patient intubation: NEVER tilt their head back because can kill them; C spine x-ray with flexion and extension to make sure they do not have this issue
Management of RA
Early RA—Patients with early disease that meet ACR criteria for the diagnosis and classification of RA and have had evidence of active disease for a period of not more than three months.
Established or persistent RA—Established RA is characterized by active, well-defined disease for at least six to twelve months. Significant and irreversible damage may be observed at this stage, leading to functional disability
Plaquenil
Least toxic of all DMARD’s and can be safely combined with others.
Works best in combination or in mild cases as monotherapy.
Dose: 200mg bid and adjusted if needed for lower weight.
Side-effects: N/V, diarrhea, HA, dizziness, myopathy, hemolysis, rash, hyperpigmentation, retinal toxicity.
Monitor: eye exam once 6mo after starting then q1yr
Is safe in pregnancy
Azulfdine
Sulfasalazine – in early disease as monotherapy usually in combinations.
Low potential toxicity.
Dose: 1-3g/day in divided doses.
Side-effects: N/V, rash, HA, dizziness, azoospermia, neutropenia, pulmonary infiltrates with eosinophilia, elevated LFT’s.
Monitor: LFT, CBC, BMP
Safe in pregnancy
