MKSAP 3: Rheumatoid arthritis

Question 1

Define RA?
What joints are typically affected?
What are the most common symptom?
What are the categories of extra-articular manifestations?

Answer 1

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.

Question 2

What is the typical epidemiology of RA?

Answer 2

1% of the population worldwide.
Women 2-3x > men
Ages 30-60 yrs

Question 3

Describe the genetic risk factors for RA?

Why do experts think it is related to presentation of specific (unidentfied) antigens?

Answer 3

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.

Question 4

What are rheumatoid factors and ant-cyclic citrullinated peptide? Which is thought to play a pathogenic role? Which is more specific to RA disease?

Answer 4

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.

Question 5

What are the environmental risk factors in RA? How does cigarette smoke possibly play a pathogenic role?

Answer 5

Smoking. Can cause citrullination of proteins in the lungs.
Asbestos, cilica. Electrical or carpentry work

Question 6

What specific organism is possibly involved in RA?

Answer 6

There is an associated b/w periodontal disease and RA. Porphyromonas gingivalis has a possible antigenic effect as it can cause citrullination of proteins.

Question 7

What is the association between women hormones and RA?

Answer 7

There is increased incidence of RA in women most evident prior to menopause, suggesting a link for sex hormones.

Question 8

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?

Answer 8

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

Question 9

What are the 4 categories applied in the RA diagnostic criteria?

Answer 9

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

Question 10

What is the typical presentation for RA?

Answer 10

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.

Question 11

What are the physical exam findings with RA? What is meant by joint symmetry?

Answer 11

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

Question 12

List the percentages of involvement of RF:
__% sensitive
__% of patients have detectable RF at onset increasing to __ - ___% in established disease
But up to __% of patients with RA lack RF

Answer 12

70% sensitive
50% at onset increasing to 60-80%
20% of patients with RA lack RF

Question 13

What are the clinical guidelines for using RF?

Answer 13

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.

Question 14

Anti-CCP is __% specific. But can occur in what other diseases?

Answer 14

95%

other rhuematologic diseases, active TB and chronic lung disease

Question 15

More than ___ of inadequately treated patients with RA develop bone erosions within the first 2 years of disease.

Answer 15

More than half

Question 16

What are the characteristic findings on XR of hands, wrists and feet?
What is the most common earliest site of bony erosion?

Answer 16

Periarticular osteopenia and marginal erosions

The fifth metatarsophalangeal joint.

Question 17

Describe use of ultrasound and MRI in diagnosing RA?

Answer 17

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

Question 18

What are the 3 extra-articular skin manifestations of RA?

Answer 18

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

Question 19

Most common extra-articular eye involvement in RA?

Answer 19

keratoconjunctivitis sicca

Question 20

What are the pulmonary involvements of RA?

Answer 20

Pleuritis (although usually asymptomatic) and exudative effusions

Question 21

RA is an independent risk factor for what cardiac diseases?

What kind of pericarditis is involved?

Answer 21

CAD and HF

Restrictive

Question 22

What is a rare complication of RA and define it?

Answer 22

Felty syndrome: neutropenia, splenomegaly, fever, anemia, thrombocytopenia and/or vasculitis and predisposes to recurrent bacterial infections
May need granulocyte stimulating factor

Question 23

Name the unusual complications of long standing, severe RA?

Answer 23

mesangioproliferative glomerulonephritis, amyloidosis, atlantoaxial subluxation, peripheral neuropathy

Question 24

What is the goal in RA drug management?

What is the name of the suggested disease assessment instrument?

Answer 24

Treat to target meaning rapidly reduce disease activity with regular follow up to assess response to treatment.
Disease Activity Score 28

Question 25

What is the recommended initial DMARD in RA?

Answer 25

methotrexate. Generally continued indefinitely and can be used alone or in combination with biologics.

Question 26

What are the next 2 best available nonbiolgoic DMARds for RA?

Answer 26

Hydroxychloroquine and sulfasalazine. May be used alone, together or in combo with methotrexate. Triple therapy has a reasonable side effect profile.

Question 27

What is the role for leflunomide in RA treatment?

Answer 27

May be used with or as a substitute for methotrexate if side effects limit use.

Question 28

How is the decision made to add a biologic DMARD to treatment? What is the guiding principle regarding biologic DMARDs in RA treatment?q

Answer 28

Based on inadequate response to nonbiologic DMARD.

Biologics are not used in combination due to the increased risk of infection.

Question 29

What are the effects of TNF alpha inhibitors? Name the agents in this class

Answer 29

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.

Question 30

What are the benefits of TNF -alphas on disease in RA?

Answer 30

Increased likelihood of achieving remission, reduction in radiographic progression, normalization of acute phase reactants and reduced CV risk. Efficacy improved with MTX.

Question 31

Name the inflammatory target pathways for the following non-TNF alpha inhibitor biologics in RA treatment

• Tocilizumab:
• Abatacept:
• Rituximab:
• Tofacitinib:

Answer 31

• 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

Question 32

When are patients considered for surgical therapy?

Answer 32

Intractable disease unresponsive to medical management. Patients with pain at rest or night pain are particularly appropriate for total joint replacement.

Question 33

Which RA meds are contraindicated in pregnancy?

Answer 33

MTX and leflunomide;

Hydroxychloroquine and sulfasalazine are considered safe in pregnancy