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Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022
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Image courtesy of Medscape | Jason Kolfenbach, MD; Kevin Deane, MD.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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
Image courtesy of John Watney | Science Source.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of LH Brent, MD.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of Medscape | David Effron, MD, FACEP.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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]
Image courtesy of Medscape.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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
Image courtesy of Centers for Disease Control and Prevention.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of LH Brent, MD.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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
Image courtesy of Biophoto Associates | Science Source.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of Science Photo Library.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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
Image courtesy of Medscape.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of Dr P Marazzi | Science Source.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of G Murali, MD.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
RA can affect the lungs in various ways,[9] including the following:
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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
Image courtesy of Wikimedia Commons | Fuse809.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of WebMD.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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.
Image courtesy of Wikimedia Commons | Vaccinationist.
Rheumatoid Arthritis: In and Out of the Joint
Herbert S Diamond, MD, MACP; Mythili Seetharaman, MD | October 21, 2022 | Contributor Information
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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Contributor Information
Author
Herbert S Diamond, MD, MACP
Visiting Professor of Medicine
Division of Rheumatology
State University of New York Downstate Medical Center
Chairman Emeritus, Department of Internal Medicine
Western Pennsylvania Hospital
Disclosure: Herbert S Diamond, MD, MACP, has disclosed no relevant financial relationships.
Coauthor
Mythili Seetharaman, MD
Consultant Rheumatologist
Orthopedic Associates of Allentown
Allentown, PA
Disclosure: Mythili Seetharaman, MD, has disclosed no relevant financial relationships.
Wechalekar MD, Lester S, Hill CL, et al. Active Foot Synovitis in Patients With Rheumatoid Arthritis: Unstable Remission Status, Radiographic Progression, and Worse Functional Outcomes in Patients With Foot Synovitis in Apparent Remission. Arthritis Care Res (Hoboken). 2016 Nov;68(11):1616-23. PMID: 26991415
Veys EM, De Keyser F. Rheumatoid nodules: differential diagnosis and immunohistological findings. Ann Rheum Dis. 1993 Sep;52(9):625-6. PMID: 8239755.
Esposito AJ, Chu SG, Madan R, et al. Thoracic manifestations of rheumatoid arthritis. Clin Chest Med. 2019 Sep;40(3)545-60. PMID: 31376890
Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD, Tanasescu R. Extra-articular manifestations in rheumatoid arthritis. Maedica (Buchar). 2010 Dec;5(4):286-91. PMID: 21977172
Kelly CA, Saravanan V, Nisar M, et al. Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study. Rheumatology (Oxford). 2014 Sep;53(9):1676-82. PMID: 24758887
Shea B, Swindon MV, Tanjong Ghogomu E, et al. Folic acid and folinic acid for reducing side in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2013 May 31;(5):CD000951. PMID: 23728635
Alcorn N, Saunders S, Madhok R. Benefit-risk assessment of leflunomide: an appraisal of leflunomide in rheumatoid arthritis 10 years after licensing. Drug Saf. 2009;32(12):1123-34. PMID: 19916579
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