
Rheumatoid Arthritis: In and Out of the Joint
Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the small joints of the hands (shown) and feet, in which synovial inflammation leads to joint erosion and deformity. It is an autoimmune condition that, although predominantly affecting joints, has systemic extra-articular manifestations as well. RA is more common in women, with the peak incidence between the ages of 35 and 50 years.[1] It is an independent risk factor for cardiovascular disease.[2]
Which of the following hand joints are usually spared in RA?
- Wrist joints
- Metacarpophalangeal (MCP) joints
- Proximal interphalangeal (PIP) joints
- Distal interphalangeal (DIP) joints
Rheumatoid Arthritis: In and Out of the Joint
Answer: D. Distal interphalangeal (DIP) joints.
Typically, RA of the hands 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.[3] All of the large peripheral joints can be involved in RA.
Rheumatoid Arthritis: In and Out of the Joint
It is essential to have the patient remove his/her shoes and socks during an examination, given that RA can involve the feet much as it does the hands.[4] Symptoms begin with pain, stiffness, swelling, and difficulty walking. Bones can shift position and cause deformities later in the disease process. Periarticular osteopenia and erosions involving the metatarsophalangeal (MTP) and interphalangeal (IP) joints (shown) can be seen. Along with aggressive RA treatment, appropriate support with orthotics should be provided.
Rheumatoid Arthritis: In and Out of the Joint
The slide shows a patient with subcutaneous nodules. The differential diagnosis for such nodules includes the following[5]:
- Rheumatoid nodules
- Gouty tophi
- Tendon xanthomas
- Malignancies
- Fibromas
- Subcutaneous granuloma annulare
- Metastatic lesions
This patient has rheumatoid nodules. These nodules are among the extra-articular manifestations of RA; they occur in seropositive RA and portend more severe RA. Rheumatoid nodules are subcutaneous, firm, nontender, and mobile. They are usually found on extensor surfaces of the elbows, fingers, or forearms, and can also occur in internal organs (eg, lungs or larynx). Methotrexate therapy can sometimes cause an increase in rheumatoid nodules.[6]
Rheumatoid Arthritis: In and Out of the Joint
The radiograph in this slide shows the hands of a patient with several years of RA. The main radiographic features of RA include the following:
- Periarticular osteopenia
- Marginal erosions
- Joint-space narrowing
- Joint destruction with deformities
- Subluxation
- Bony ankylosis
Rheumatoid Arthritis: In and Out of the Joint
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.
Tumor necrosis factor (TNF) antagonists (eg, infliximab) and other biologic disease-modifying antirheumatic drugs (DMARDs) used to treat RA are associated with an increased risk of tuberculosis (TB) reactivation. Before initiation of biologic therapy (eg, with infliximab), 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.
Rheumatoid Arthritis: In and Out of the Joint
A 45-year-old woman who has longstanding seropositive RA with nodules presents with pain and discoloration of one of her fingers.
Which of the following is the most likely diagnosis?
- Rheumatic fever
- Infective endocarditis
- Anti–phospholipid antibody syndrome
- Rheumatoid vasculitis
Rheumatoid Arthritis: In and Out of the Joint
Answer: D. Rheumatoid vasculitis.
Rheumatoid vasculitis is a rare manifestation of RA.[7] Small-vessel vasculitis usually involves the skin; large-vessel vasculitis can mimic polyarteritis nodosa. Biopsy of the skin shows leukocytoclastic vasculitis. Nerve biopsy may be needed to evaluate 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.
Rheumatoid Arthritis: In and Out of the Joint
A 70-year-old man with well-controlled RA (on a regimen of methotrexate weekly, subcutaneous adalimumab every 2 weeks, and prednisone 5 mg/day) presents with a painful, swollen right knee joint of 3 days' duration. 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 show chronic synovitis in the wrists, the MCP joints, and the PIP joints.
Which of the following is the most appropriate next step in management?
- Initiation of corticosteroids for possible RA flare
- Magnetic resonance imaging (MRI) of the right knee
- Joint aspiration and fluid analysis
- Intra-articular injection of corticosteroids
- Lyme titer
Rheumatoid Arthritis: In and Out of the Joint
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.[8] RA flare can be considered as the etiology once infection has been clearly ruled out.
Rheumatoid Arthritis: In and Out of the Joint
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 morning stiffness for the past month and has made an appointment to be evaluated.
The diagnosis is episcleritis, a condition characterized by redness (shown), engorged episcleral vessels, absence of tenderness, and normal vision. Episcleritis can be associated with systemic diseases such as RA and lupus; other manifestations include dry eyes and scleritis. Episodes can be recurrent. Episcleritis responds to treatment with topical lubricants, nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids.
Rheumatoid Arthritis: In and Out of the Joint
RA can affect the lungs in various ways,[9] including the following:
- Exudative pleural effusion
- Interstitial lung disease (ILD) - Usual interstitial pneumonia; nonspecific interstitial pneumonia (shown)
- Rheumatoid nodules
- Pulmonary hypertension
- Bronchiolitis obliterans
- Drug-related lung disease
- Infection
Rheumatoid Arthritis: In and Out of the Joint
In managing rheumatoid lung disease, the following key points should be kept in mind:
- Rheumatoid nodules occur more commonly in men,[10] 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 ILD as a consequence of citrullination of proteins in the lungs[11]
- Pulmonary hypertension in RA is rare
- Methotrexate-induced lung disease is a diagnosis of exclusion
- Infection—in particular, mycobacterial disease—must be ruled out in RA patients who have been treated with TNF inhibitors and other biologic agents
Rheumatoid Arthritis: In and Out of the Joint
To decrease toxicity, folic acid should be taken with methotrexate (molecular model shown). Methotrexate is a folate antagonist.[12] Folic acid supplementation decreases gastrointestinal and liver toxicity associated with methotrexate, as well as cytopenia. It also offsets methotrexate-induced elevation in homocysteine, decreasing cardiovascular risk. Folic acid does not decrease the efficacy of methotrexate.
Rheumatoid Arthritis: In and Out of the Joint
With regard to management of RA in pregnancy, methotrexate and leflunomide[13] are classified as category X agents and thus should not be administered to pregnant women. 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.
Rheumatoid Arthritis: In and Out of the Joint
A 35-year-old woman with a 10-year history of RA was receiving methotrexate, hydroxychloroquine, and sulfasalazine but was switched to leflunomide 2 months previously because of active RA symptoms in her hands and feet. She has had nausea, fatigue, and weight loss for the past few weeks. Her RA has improved. Laboratory values are as follows: aspartate transaminase (AST)/alanine transaminase (ALT), 163/224; bilirubin, 1.5; albumin, 2.6; alkaline phosphatase, 130; hemoglobin, 11; white blood cell count, 3; platelet count, 150; erythrocyte sedimentation rate, 3; and C-reactive protein, 7.
Leflunomide (shown) is an immunomodulatory agent used as a DMARD in RA at dosages of 10-20 mg/day. Side effects include rash, fever, nausea, diarrhea, and hepatotoxicity.[1] AST/ALT may be transiently elevated up to one to two times the normal level. However, severe liver injury due to toxic intermediates can occur, and close monitoring of liver function is therefore necessary.
After leflunomide is discontinued and supportive care initiated, the next step in management is to administer cholestyramine. Because of the long half-life and enterohepatic circulation of leflunomide, discontinuance alone does not clear the drug rapidly enough, and a bile acid resin such as cholestyramine must be administered to speed clearance.
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