Rheumatoid Arthritis

Contributor: Jessica Berman, MD

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A 20 year old female comes to see you because 4 months ago she began having pain and stiffness in the MCPs and wrists. The symptoms are worse in the morning lasting for 1 hour and improve with movement. There is fatigue but no other problems identified on review of systems. On exam the wrists are slightly swollen and tender and MCPs are tender but not swollen. ESR is 48. The rheumatoid factor (RF) is positive at 105 and the anti-cyclic citrullinated peptide (anti-CCP or ACPA) is >250. X-rays show peri-articular osteopenia but no erosions.

What is the significance of the tests ordered in making the diagnosis of RA?

  • Antibodies commonly checked when RA is suspected include rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody. Presence of these antibodies is predictive of more aggressive disease and may prompt more aggressive treatment. Anti-CCP is more specific for RA than RF. It is important to remember that RA is a clinical diagnosis and that antibody positivity is not necessary in order to make a diagnosis. This is called "seronegative RA". The 2010 Classification Criteria for RA are used to enroll patients in clinical trials and caution should be used when approaching patients in clinical practice.
  • Rheumatoid arthritis is a chronic, progressive inflammatory disease affecting primarily the small joints of the hands, feet, wrists and ankles in a symmetric fashion and characterized by the presence of erosions on radiographs. The presence of erosions on x-ray is pathognomonic for the diagnosis of RA. It is said that up to 80% of patients with RA will have erosions within the first 3 months of their illness. However, early on in the disease they are not always present and soft tissue swelling only may be the only manifestation.
  • Although the erythrocyte sedimentation rate (ESR) is often elevated in patients with RA, especially with active polyarthritis, patients can have signs of active inflammation and a normal ESR. However, a high ESR is a marker for systemic inflammation and is probably indicative of an overall worse prognosis.

What are the typical features seen in this patient that are helpful in making the diagnosis of RA?

This patient clinically has diffuse MCP and wrist synovitis which is indicative of RA. It is important to remember that RA is a clinical diagnosis. Other findings which support the diagnosis besides the presence of symmetrical small joint arthritis include the presence of osteopenia on x-ray and the high ESR. Since anti-CCP is highly specific for the disease it adds to the weight of the diagnosis. The presence of RF and anti-CCP put this patient at high risk for progression and should be considered when making treatment decisions.


A 58-year old woman was diagnosed with RA 15 years ago when she first presented with 16 tender and 12 swollen joints including the MCPs, PIPs, and wrists. At that time she was treated with hydroxychloroquine, sulfasalazine, and methotrexate without improvement. Past medical history is notable for HTN and a smoking history of 1ppd x 10 years.

On exam today, the patient shows the typical signs of RA with bilateral flexion deformities of the fingers and ulnar drift at the wrists. There is evidence of active synovitis in the left 2nd MCP only.

The following labs are obtained: ESR is 6 mm/hr, RF is positive at 105 and CCP is positive at >250. X-rays show multiple erosions in the MCPs and the wrists. The patient is currently on prednisone 15mg PO daily, methotrexate 20mg PO weekly and etanercept 50mg SQ weekly. The etanercept was added 6 months ago. The patient continues to have AM stiffness lasting longer than 2 hours and is unable to perform ADLs. The option for other treatments is discussed.

What are infection risks for this patient given the current therapy?

  • Etanercept blocks tumor necrosis factor (TNF) and is immunosuppressive, placing patients at higher risk for infections, particularly, skin and respiratory infections. Because this therapy blocks the formation of granulomas, a process important in containing tuberculosis, documenting that a patient is negative for tuberculosis exposure prior to starting therapy is mandatory.
  • RA patients should be monitored closely for the signs and symptoms of infection, particularly respiratory and skin infections and should receive immunizations for influenza and pneumococcal pneumonia.

What does this patient need to know about their risk for heart disease and for the risk of malignancy?

  • Heart disease is more likely to occur in patients who have RA that is not effectively controlled due to ongoing inflammation. Clinicians should consider RA a risk factor for the development of cardiovascular disease.
  • Some studies to date have shown that RA patients on anti-TNF medications have a slightly higher risk for developing lymphoma. However, this is true of most medications used to treat RA and may indicate that it is the inflammation and not a particular drug that causes this. Patients may also have a slightly higher risk of non-melanoma skin cancers. In some studies this risk of malignancy did not appear to be statistically significant.

Patient Care

  1. Recognize the existence the 2010 Criteria for RA.
  2. Recognize the epidemiology of RA.
  3. Determine the most appropriate work up (serologic and radiographic testing) for a patient with polyarthritis.
  4. Recognize that smoking is a risk factor for more aggressive or treatment-resistant RA.
  5. Recognize the increased risk of cardiovascular disease in RA.
  6. Identify the need for PPD testing prior to initiating anti-TNF medications.

Medical Knowledge

  1. Recognize the differential diagnosis of polyarticular joint pain in an adult, and the most commonly involved joints in RA.
  2. Demonstrate how to test for an intra-articular effusion in the knee.
  3. Recognize that limitation in passive ROM represents intra-articular pathophysiology; active ROM extra-articular and differentiate between prepatellar bursitis and an intra-articular knee effusion.
  4. Distinguish between Swann-neck and Boutonniere's deformities.
  5. Describe the most common location for rheumatoid nodules and describe the histopathology of a nodule.
  6. Explain the significance of seropositivity as a risk for more aggressive disease and the significance of RF and CCP antibodies.
  7. Describe two extra-articular manifestations of RA (i.e., lung nodules, scleritis, episcleritis, amyloidosis).
  8. Locate and describe erosions on plain films of the hands.
  9. Identify the drugs most commonly used to treat RA and their main toxicities.

Interpersonal and Communication Skills

  1. Propose a standard of care treatment for a patient with newly diagnosed, erosive, seropositive RA.
  2. Summarize the common side effects of oral steroids for a patient who has never taken them.
  3. Recognize that NSAIDS and steroids are not appropriate monotherapy and contrast their use with the benefits of DMARDS for the patient.
  4. Discuss with a patient the factors that go into making the decision to replace a joint.


  1. Recognize the needs of a patient with a chronic disease and the effect on family and work performance.
  2. Understand the need to provide supportive, ongoing care.
  3. Describe the treatment issues of a young female who wants to become pregnant.
  4. Consent a patient for intra-articular steroid injection and discuss the indications for use.

Problem-Based Learning

  1. Recognize that a normal ESR does not negate the findings of inflammation on exam.
  2. Explain how RF and CCP antibodies may impact on treatment decisions.
  3. Explain any hereditary factors and HLA associations involved in disease.
  4. Apply information about the joint exam and patient VAS to calculate a DAS 28 and understand the utility of a DAS 28 and a CDAI.
  5. Apply information obtained on x-ray regarding disease severity to make decisions about appropriate care for the patient.

System Based Practice

  1. Implement a cost-effective therapy in a newly diagnosed RA patient.
  2. Demonstrate the ability to interact with physical and occupational therapists to enhance the care of patients with RA.
  3. Recognize the factors that lead to disability in patients with deforming RA.
  4. Incorporate considerations of cost and risk-to-benefit ratios in clinical evaluations, monitoring and therapeutic decisions, for the individual patient.

Key References


(Answer questions 1 – 5 on a piece a paper. Find Answer Key at the bottom on the page.)

1. A 40-year woman comes in with 4 months of worsening joint pain and swelling of the small joints of the hands, wrists, feet and ankles, severe fatigue, and 2 hours of morning stiffness which improves as the day goes on and with movement. You obtain an x-ray of the hands and wrists that demonstrates diffuse osteopenia and marginal erosions in the MCPs and carpal bones of the wrist.

The test which has the greatest specificity for this patient’s diagnosis is:

  1. Rheumatoid factor (RF)
  2. HLA-B27
  3. Anti-CCP antibody (CCP)
  4. ANA
  5. Double stranded DNA (dsDNA)

2. A 50 year old with a long history of Rheumatoid Arthritis on methotrexate and etanercept calls to report 3 days of gradually worsening knee pain with swelling, difficulty bending the knee and trouble weight bearing. The knee appears red. All of the other joints that have been previously active are asymptomatic.

The next best management for this patient is:

  1. Plain films of the knee
  2. Aspirate the joint
  3. Start high dose steroids
  4. Increase the methotrexate dose
  5. MRI of the knee

3. A 35 year old with RA currently treated with methotrexate alone, previously with good control, comes in to see you with new and painful red right eye. On exam the eye is read with limbal sparing. The patient is sensitive to light and pressure on the globe produces pain.

Which of the following eye complications would most likely be seen in a patient with active Rheumatoid Arthritis?

  1. cataract
  2. scleritis
  3. uveitis
  4. conjunctivitis

4. You are seeing a 60-year-old patient with longstanding erosive RA, on methotrexate with a positive RF and CCP who comes in to see you because he noted several swellings on the extensor surface of the elbow. On exam, these appear to be flesh colored and are moveable, with a rubbery feel. They are nontender.

The histology which best represents the pathophysiology of these nodule is:

  1. pallisading histiocytes
  2. septal panniculuitis
  3. neutrophilic infiltrate
  4. Negatively birefringent crystals
  5. Prior to undergoing surgery in which general anesthesia is required all RA patients should undergo the following testing:
  6. C-spine x-ray
  7. Lumbar x-ray
  8. Pulmonary function testing
  9. Lower extremity dopplers

Answer Key

1) The correct answer is C.

CCP antibody is the most sensitive test for the diagnosis of RA with a sensitivity and specificity of greater than 98%. RF is much less specific and only about 60% sensitive. ANAs can be seen in RA in addition to lupus and other connective tissue disease so is not specific for the diagnosis. HLAB27 can be seen in association with seronegative arthritis. Double stranded DNA is specific for lupus and is not seen in RA.

2) The correct answer is B.

The next best step is to aspirate the joint to rule out infection, particularly since there is one joint out of proportion to the rest. Patients on immunosuppressive therapy sometimes fail to present with the common signs of infection (i.e., fever) and suspicion as such should be high. Aspiration is the only way to diagnose infection in this patient. X-rays and MRI may show an effusion but cannot definitively diagnose infection. Increasing methotrexate or adding steroids until infection is ruled out would be wrong.

3) The correct answer is B.

This patient has scleritis, which can be seen in up to 1% of RA patients. Uveitis is a more common problem in patients with seronegative arthritis such as spondyloarthritis or psoriatic arthritis. A cataract can be seen in patients with RA, particularly as a result of treatment with steroids, however it is not commonly due to the disease itself. Conjunctivitis is an infectious complication of the eye and would be due to immunosuppression, not the underlying disease.

4) The correct answer is A.

These are subcutaneous nodules, more common in more severe RA patients who, like this patient are seropositive for RF and/or CCP antibodies. Nodules may be a sign of more active disease. They can occur in 20-35% of patients. The most common location is on the extensor surfaces of the elbows. Methotrexate is thought to accelerate nodule formation in some patients. On histology pallisading histiocyles can be seen. Septal panniculitis is seen with E nodousm. Crystals would be indicative of gout.

5) The correct answer is A.

All patients with RA should have an x-ray of the cervical spine prior to undergoing surgery to rule out instability. X-ray should be ordered with flexion and extension views to evaluate for atlanto-axial subluxation. Lumbar spine is not affected in RA so would not be indicated. PFTs would not be required unless there is a history of underlying lung disease. Dopplers wouldn’t be needed since RA patients are not necessarily thought to have increased hypercoaguable risk.

Last updated February 2015

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