A 55-year-old business executive comes to the office due to worsening joint pains for the past several months. He says, "My hands and fingers feel tight on waking up in the morning, and they are painful to move. I can't hold my toothbrush or button up my shirts. It slowly gets better by the time I get to the office in the morning." The patient has also felt excessively tired and has lost 4.5 kg (10 lb) over the past 6 months, which he attributes to extra work for a new business venture. He has no prior medical problems and takes no medications. The patient occasionally drinks alcohol and does not use tobacco or illicit drugs. Temperature is 37.2 C (99 F), blood pressure is 132/86 mm Hg, and pulse is 72/min. Physical examination shows no scleral icterus or oral lesions. The lungs are clear to auscultation. Heart sounds are normal. The abdomen is soft and nontender with no organomegaly. Metacarpophalangeal and proximal interphalangeal joints of both hands show mild boggy swelling with tenderness on gentle squeezing. There is no increased joint warmth or erythema. No skin rashes are present. Laboratory results are as follows.
| Erythrocyte sedimentation rate | 80 mm/hr |
| Rheumatoid factor | negative |
| Antinuclear antibody | negative |
Which of the following is the most appropriate next step in evaluation of this patient?
Clinical features of rheumatoid arthritis | |
Clinical presentation |
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Laboratory/ |
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anti–CCP = anti–cyclic citrullinated peptide; DIP = distal interphalangeal; ESR = erythrocyte sedimentation rate; MCP = metacarpophalangeal; MTP = metatarsophalangeal; PIP = proximal interphalangeal. | |
This patient has a prolonged morning stiffness and a chronic symmetric polyarthritis with synovitis (bogginess on examination) predominantly involving the proximal interphalangeal and metacarpophalangeal joints. In association with the elevated erythrocyte sedimentation rate and systemic symptoms (ie, fatigue, weight loss), this presentation suggests rheumatoid arthritis (RA).
RA is diagnosed primarily based on clinical findings; however, serologies can help clarify the diagnosis.
In patients in whom RA is suspected but who have a negative RF test result, anti-CCP testing should be obtained. Seronegative RA (ie, negative assays for RF and anti-CCP) often carries a better prognosis; however, many patients with initially seronegative disease will develop positive markers later in their course.
(Choice B) Anti–double-stranded DNA antibodies are primarily used to evaluate systemic lupus erythematosus (SLE). They have higher specificity for SLE than antinuclear antibodies (ANA) but lower sensitivity. SLE can cause arthritis and constitutional findings (eg, weight loss), but the patient has no other manifestations of SLE. In addition, if ANA is negative, as in this patient, further serologic testing for SLE is not needed.
(Choice C) Hypertrophic osteoarthropathy is a paraneoplastic syndrome associated with intrathoracic malignancy and other pulmonary diseases (eg, cystic fibrosis) that could be apparent on CT scan. However, although it can cause a polyarthropathy, it is also associated with digital clubbing and periostosis (excessive bone formation).
(Choices D and E) Spondyloarthropathies (eg, ankylosing spondylitis, reactive arthritis) are associated with HLA-B27 and are characterized by asymmetric oligoarthritis involving the large joints (eg, knees), enthesitis (inflammation at the insertion of ligaments and tendons), and back pain. Hand involvement is rare. Reactive arthritis typically occurs acutely following a gastrointestinal or genitourinary infection (eg, Chlamydia trachomatis) and resolves within a few months.
(Choice F) Parvovirus B19 causes a symmetric arthritis that affects the hands, knees, and feet. It may resemble RA, but the symptoms usually resolve spontaneously within a few weeks.
(Choice G) Gout is caused by deposition of uric acid crystals in the synovial space; the incidence correlates roughly with serum uric acid levels. However, gout most commonly presents with episodic acute monoarthritis, with dramatic redness and warmth involving the toes, ankles, or knees.
Educational objective:
Rheumatoid arthritis (RA) causes a chronic, symmetric polyarthritis predominantly affecting the small joints of the hands. Rheumatoid factor (low specificity) and cyclic citrullinated peptide antibodies (high specificity) are the primary serologic markers for RA. Patients who have negative assays for both markers (seronegative RA) may have a more favorable prognosis.