Rheumatoid Arthritis: In and Out of the Joint

Mythili Seetharaman, MD | June 9, 2015

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Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the small joints of the hands and
feet, in which synovial inflammation leads to joint erosion and deformity. It is an autoimmune
condition that, besides affecting joints, also has systemic extra-articular manifestations. RA is
more common in women older than 40 years. It is an independent risk factor for cardiovascular
disease.[1]
Image courtesy of Guniita | Hriana | Dreamstime.

The slide shows a patient with RA affecting the hands. Which of the hand joints are usually
spared in RA?
A. Wrist joints
B. Metacarpophalangeal (MCP) joints
C. Proximal interphalangeal (PIP) joints
D. Distal interphalangeal (DIP) joints
Image courtesy of Mythili Seetharaman, MD.

Answer: D. Distal interphalangeal (DIP) joints.

Typically, RA involves the wrists, the MCP joints, and the PIP joints while sparing the DIP
joints. In contrast, osteoarthritis affects the PIP and DIP joints. RA also spares the spine, except
for the cervical spine. All of the large peripheral joints can be involved in RA.
Image courtesy of Mythili Seetharaman, MD.

The slide shows a patient with subcutaneous nodules. What is the differential diagnosis for such
nodules?
Image courtesy of LH Brent, MD.

The differential diagnosis for subcutaneous nodules includes the following[2]:

Rheumatoid nodule

Gouty tophus

Tendon xanthoma

Malignancy

Fibroma

Subcutaneous granuloma annulare

Metastatic lesions

The patient shown in the slide has rheumatoid nodules.

Image courtesy of LH Brent, MD.

Rheumatoid nodules are among the extra-articular manifestations of RA; they occur in
seropositive RA and portend more severe RA. These nodules are subcutaneous, firm, nontender,
and mobile. Although they usually present on extensor surfaces of the elbows, fingers, or
forearms, they can also occur in internal organs (eg, lungs or larynx). Methotrexate therapy can
sometimes cause an increase in rheumatoid nodules.
Image courtesy of Medscape.

The slide shows a radiograph of the right hand of a 71-year-old woman with RA. What are the
main features of RA on radiography?
Image courtesy of LH Brent, MD.

Radiographic features of RA include the following:

Periarticular osteopenia

Marginal erosions

Joint-space narrowing

Joint destruction with deformities

Subluxation

Bony ankyloses

Image courtesy of LH Brent, MD.

In 2010, the American College of Rheumatology (ACR) and the European League Against
Rheumatism (EULAR) published criteria for RA diagnosis (shown).[3] The diagnosis is
determined on the basis of a score-based algorithm. The scores for four individual factors (joint
involvement, serology, acute-phase reactants, and symptom duration) are added; the maximum
possible total score is 10. For a definite diagnosis of RA, a total score of 6 or higher is required.
ACPA = anticitrullinated protein antibody; CRP = C-reactive protein; ESR = erythrocyte
sedimentation rate; RF = rheumatoid factor.
Adapted from Aletaha D et al.[3]

A 55-year-old woman with RA of 2 years' duration has active synovitis despite treatment with
hydroxychloroquine, sulfasalazine, and prednisone. Her purified protein derivative (PPD)
tuberculin test result is positive, with 14 mm induration.
Which of the following RA medications must be used with caution in this patient?
A. Methotrexate
B. Hydroxychloroquine
C. Infliximab
D. Sulfasalazine
Image courtesy of Alila07 | Dreamstime.

Answer: C. Infliximab.
Tumor necrosis factor (TNF) antagonists and other biologic disease-modifying antirheumatic
drugs (DMARDs) used to treat RA are associated with an increased risk of tuberculosis (TB)
reactivation. Accordingly, before initiation of biologic therapy, all patients should be routinely
screened for latent TB with PPD testing (shown) or interferon gamma release assay and chest
radiography. Patients with latent TB should be treated for at least 6 months before biologic
therapy is started.
Image courtesy of Centers for Disease Control and Prevention.

A 45-year-old woman who has longstanding seropositive RA with nodules presents with pain and
discoloration in one of her little fingers.
Which of the following is the most likely diagnosis?
A. Rheumatic fever
B. Infective endocarditis
C. Antiphospholipid antibody syndrome
D. Rheumatoid vasculitis
Image courtesy of LH Brent, MD.

Answer: D. Rheumatoid vasculitis.

Rheumatoid vasculitis is a rare manifestation of RA.[4] Small-vessel vasculitis usually involves
the skin; large-vessel vasculitis can mimic polyarteritis nodosa. Biopsy of the skin shows
leuckocytoclastic vasculitis. Nerve biopsy may be needed for nerve involvement, and abdominal
angiography may be required if an internal organ is involved. Treatment is based on the severity
of the illness. Underlying RA should be well controlled.
Image courtesy of LH Brent, MD.

A 70-year-old man with well-controlled RA (on a regimen of methotrexate weekly, subcutaneous

adalimubab every 2 weeks, and prednisone 5 mg/day) presents with a painful, swollen right knee
joint, which he has had for the past 3 days. There is no history of trauma, fever, or pain in any
other joints. Examination reveals a moderate-sized right knee effusion with warmth, tenderness,
and limited range of motion. The patient's hands showed chronic synovitis in the wrists, the MCP
joints, and the PIP joints.
Which of the following is the most appropriate next step in management?
A. Initiation of corticosteroids for possible RA flare
B. Magnetic resonance imaging (MRI) of the right knee
C. Joint aspiration and fluid analysis
D. Intra-articular injection of corticosteroids
E. Lyme titer
Image courtesy of Science Photo Library.

Answer: C. Joint aspiration and fluid analysis.

Infection should always be suspected in any monoarthritis, even against a background of RA,
particularly in patients receiving immunosuppressive therapy. Absence of fever does not exclude
infection. It is important to start empiric antibiotic therapy for septic arthritis while awaiting
culture results. Staphylococcus aureus is the organism that most commonly causes septic
arthritis. RA flare can be considered as the etiology once infection has been clearly ruled out.
Image courtesy of Medscape.

A 55-year-old woman presents with a 2-day history of redness and discomfort in the left eye.
There has been no change in her vision, and she denies having any photophobia. Last year, the
patient had one similar episode in the same eye. She complains of experiencing pain in her hands
with arm stiffness for the past month and has made an appointment to be evaluated.
What is the diagnosis?
Image courtesy of LH Brent, MD.

The diagnosis is episcleritis, a condition characterized by redness, engorged episcleral vessels,

absence of tenderness, and normal vision. Recurrent episodes may be noted. Episcleritis can be
associated with systemic diseases such as RA and lupus; other manifestations include dry eyes
and scleritis. Episcleritis responds to treatment with topical lubricants, nonsteroidal antiinflammatory drugs (NSAIDs), and steroids.
Image courtesy of LH Brent, MD.

RA can affect the lungs in various ways,[5] including the following:

Exudative pleural effusion

Interstitial lung disease - Usual interstitial pneumonia; nonspecific interstitial pneumonia

(shown)

Rheumatoid nodules

Pulmonary hypertension

Bronchiolitis obliterans

Drug-related lung disease

Infection

Image courtesy of G Murali, MD.

In managing rheumatoid lung disease, the following key points should be kept in mind:

Rheumatoid nodules occur more commonly in men, and malignancy must be excluded

With rheumatoid pleural effusions, glucose levels in the pleural fluid are low because of a
glucose transporter defect

Smokers with RA develop interstitial lung disease (ILD) as a consequence of

citrullination of proteins in the lungs

Pulmonary hypertension in RA is rare

Methotrexate-induced lung disease is a diagnosis of exclusion

Infectionin particular, mycobacterial diseasemust be ruled out in RA patients who

have been treated with TNF inhibitors and other biologic agents

With regard to management of RA in pregnancy, which of the following statements is correct?

A. Methotrexate is contraindicated
B. Infliximab is teratogenic
C. Leflunomide is safe in pregnancy
D. RA flares during pregnancy and improves after delivery
Image courtesy of Petro | Melodija | Dreamstime.

Answer: A. Methotrexate is contraindicated.

Methotrexate and leflunomide are classified as category X agents and thus should not be used
during pregnancy. TNF inhibitors (eg, infliximab, etanercept, and adalimumab) and calcineurin
inhibitors (eg, tacrolimus and cyclosporine) may be continued during pregnancy. Abatacept,
rituximab, and mycophenolate must be withdrawn before pregnancy. Usually, RA improves
during pregnancy and flares after delivery.
Image courtesy of WebMD.
http://reference.medscape.com/features/slideshow/rheumatoid-arthritis#page=21