Flashcards in MKSAP 3: Rheumatoid arthritis Deck (33):
What joints are typically affected?
What are the most common symptom?
What are the categories of extra-articular manifestations?
A systemic autoimmune disorder of unknown cause that typically presents as a symmetric inflammatory polyarthritis.
The PIPs and MCPs of the hands and the wrists
Prolonged morning stiffness
Inflammation of the skin, eyes, pleura and pericardium.
What is the typical epidemiology of RA?
1% of the population worldwide.
Women 2-3x > men
Ages 30-60 yrs
Describe the genetic risk factors for RA?
Why do experts think it is related to presentation of specific (unidentfied) antigens?
Siblings have 2x the risk and offspring have 3x the risk
Twin studies: 60% heritability
Alleles encoding the shared epitope that demonstrate the strongest association with RA, corresponds to a specific amino acid sequence in the antigen binding site of the MHC molecule.
What are rheumatoid factors and ant-cyclic citrullinated peptide? Which is thought to play a pathogenic role? Which is more specific to RA disease?
Both are autoantibodies; may proceed disease by years neither are diagnostic
RF: immunoglobulin directed against Fc portion of IgG, associated with increased risk of diagnosis and widespread joint disease
Anti-CCP: antibodies against citrullinated proteins including proteins in inflammed joint tissue. More specificity. Greater risk of erosive disease and radiographic progression.
What are the environmental risk factors in RA? How does cigarette smoke possibly play a pathogenic role?
Smoking. Can cause citrullination of proteins in the lungs.
Asbestos, cilica. Electrical or carpentry work
What specific organism is possibly involved in RA?
There is an associated b/w periodontal disease and RA. Porphyromonas gingivalis has a possible antigenic effect as it can cause citrullination of proteins.
What is the association between women hormones and RA?
There is increased incidence of RA in women most evident prior to menopause, suggesting a link for sex hormones.
Table 13 Rheum.
What is the name of the grading system for making a diagnosis of RA?
What are the first 2 questions whether to apply the criteria to a patient?
2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA
1) at least 1 joint with definite clinical synovitis
2) with synovitis not better explained by another disease
What are the 4 categories applied in the RA diagnostic criteria?
1) # of involved joints
2) Serology (RF & anti-CCP)
3) Acute phase reactants (CRP/ESR)
4) Duration of joint involvement +/- 6 weeks
A score of >6/10 is needed, and score can change over time
What is the typical presentation for RA?
Pain and swelling in multiple >3 small joints of the hands or feet along with morning stiffness lasting at least 1 hour. DIP is distinctly rate.
Worsen over weeks to months, rarely abrupt onset.
Constitutional symptoms: increased fatigue, malaise, depression, myalgia, fever, anorexia, weight loss.
What are the physical exam findings with RA? What is meant by joint symmetry?
Tenderness and swelling the joints sometimes with warmth and erythema
Joint symmetry refers to involvement of the same rank of joints on both sides.
Needs to be at least 6 weeks involvement
List the percentages of involvement of RF:
__% of patients have detectable RF at onset increasing to __ - ___% in established disease
But up to __% of patients with RA lack RF
50% at onset increasing to 60-80%
20% of patients with RA lack RF
What are the clinical guidelines for using RF?
The PPV of RF is low in patients with a low pre-test probability of disease. Testing patients with fibro, osteo or nonspecific aches and pains is not recommended
Fluctuations in RF do not mirror disease activity and serial testing lacks clinical utility in established disease.
Anti-CCP is __% specific. But can occur in what other diseases?
other rhuematologic diseases, active TB and chronic lung disease
More than ___ of inadequately treated patients with RA develop bone erosions within the first 2 years of disease.
More than half
What are the characteristic findings on XR of hands, wrists and feet?
What is the most common earliest site of bony erosion?
Periarticular osteopenia and marginal erosions
The fifth metatarsophalangeal joint.
Describe use of ultrasound and MRI in diagnosing RA?
US is increasingly utilized but requires special training and is operator dependent and may not be more specific than XR
MRI is sensitive for identifying erosions but is listed on the college of rheum's Choosing Wisely list not to use MRI to monitor RA. Can be used for eval of c-spine
What are the 3 extra-articular skin manifestations of RA?
1) rheumatoid nodules: most frequent, firm, subQ masses may be mobile or adhere to periosteum, on pressure areas but also on lungs, heart and muscle.
2) Pyoderma gangrenosum: single painful lesion of the LEs, starts as tender erythematous or violaceous papule and expands into purulent, necrotic, nonhealing ulcer.
3) Rheumatoid vasculitis: small and medium sized vessels and may involve skin of other organs, most common in seropositive males with long standing disease
Small vessel: purpura, petechiae, splinter hemmorhages, naifold infarctions, peripheral neuropathy
Medium sized vessels: nodules, ulcerations, livedo reticularis, digital infarcts
Most common extra-articular eye involvement in RA?
What are the pulmonary involvements of RA?
Pleuritis (although usually asymptomatic) and exudative effusions
RA is an independent risk factor for what cardiac diseases?
What kind of pericarditis is involved?
CAD and HF
What is a rare complication of RA and define it?
Felty syndrome: neutropenia, splenomegaly, fever, anemia, thrombocytopenia and/or vasculitis and predisposes to recurrent bacterial infections
May need granulocyte stimulating factor
Name the unusual complications of long standing, severe RA?
mesangioproliferative glomerulonephritis, amyloidosis, atlantoaxial subluxation, peripheral neuropathy
What is the goal in RA drug management?
What is the name of the suggested disease assessment instrument?
Treat to target meaning rapidly reduce disease activity with regular follow up to assess response to treatment.
Disease Activity Score 28
What is the recommended initial DMARD in RA?
methotrexate. Generally continued indefinitely and can be used alone or in combination with biologics.
What are the next 2 best available nonbiolgoic DMARds for RA?
Hydroxychloroquine and sulfasalazine. May be used alone, together or in combo with methotrexate. Triple therapy has a reasonable side effect profile.
What is the role for leflunomide in RA treatment?
May be used with or as a substitute for methotrexate if side effects limit use.
How is the decision made to add a biologic DMARD to treatment? What is the guiding principle regarding biologic DMARDs in RA treatment?q
Based on inadequate response to nonbiologic DMARD.
Biologics are not used in combination due to the increased risk of infection.
What are the effects of TNF alpha inhibitors? Name the agents in this class
Adalimumab (Humira); Etanercept (Enbrel); Certolizumab pegol (Cimzia); Golimumab (Simponi); Infliximab (Remicade)
Interferes with TNF alpha, a proinflammatory cytokine which stimulates synovial cell proliferation, synthesis of collagenase (cartilage damage), increased bone resorption, inhibits proteoglycan synthesis and increases expression of adhesion molecules.
What are the benefits of TNF -alphas on disease in RA?
Increased likelihood of achieving remission, reduction in radiographic progression, normalization of acute phase reactants and reduced CV risk. Efficacy improved with MTX.
Name the inflammatory target pathways for the following non-TNF alpha inhibitor biologics in RA treatment
- Tocilizumab (Actemra): monclonal ab that neutralizes IL-6 (activates T cells, B cells, macrophages, osteoclasts and hepatic acute phase response)
- Abatacept (Orencia): blocks necessary second signals b/w antigen presenting cells and T cells during antigen presentation
- Rituximab (Rituxan): monoclonal ab that depletes B cell populations leading to reduction in B cell cytokine production
- Tofacitinib (Xeljanz): first small molecule oral agent that inhibits JAK-STAT pathways of inflammation
When are patients considered for surgical therapy?
Intractable disease unresponsive to medical management. Patients with pain at rest or night pain are particularly appropriate for total joint replacement.