Antinuclear antibody (ANA) measurement, complete blood cell (CBC) count, platelet count, serum uric acid measurement, and HLA tissue testing aid in the differential diagnosis of RA and distinguish it from other arthritic and immunologic pathologies. Leukocytosis (white blood cell [WBC] count >11,000/μL) and thrombocytosis (platelet count ≥450 × 109/L) are commonly noted in the CBC count.13 Iron levels should be monitored because a moderate hypochromic normocytic anemia is commonly seen in RA. The joint fluid should be assessed to quantify inflammation and rule out gout or septic arthritis. Whereas osteoarthritic joint fluid typically appears yellow, RA joint fluid tends to be more yellow to opalescent, with a higher WBC count and platelet count than osteoarthritic joint fluid.2 Arthrocentesis is a needed diagnostic measure to rule out septic arthritis, a severe complication of RA. Clinicians should suspect septic arthritis when one joint is significantly more inflamed than other problematic joints.5

Radiographic changes are the most specific diagnostic measure for RA and are therefore of the utmost importance. Although little radiologic change is observed in the first 6 months after onset, initial changes are noted in the hands and feet as the soft tissue swells and juxta-articular demineralization occurs. As the disease progresses, decreased joint spaces and erosive processes become evident. The ulnar styloid and juxta-articular margins are the loci where bone erosion is often first identified on radiographs. Although magnetic resonance imaging and ultrasonography are more sensitive than radiography, the value of these modalities in the diagnosis of early RA has yet to be determined in comparison with plain film.5

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Treatment options 

If RA is suspected, the patient should promptly be referred to a rheumatologist for diagnosis, treatment initiation, and the development of a long-term strategy. Treatment should be initiated as soon as a diagnosis has been established to diminish pain, preserve joint function, and avoid future/further deformity. Besides pharmacologic treatment, the patient should be referred to physical and occupational therapy for holistic benefit.2

Disease-modifying antirheumatic drugs (DMARDs) are the established initial treatment for RA. This pharmacologic class has been shown to have a suppressive effect on disease activity. The DMARD of choice is methotrexate (MTX). Positive effects usually are noticed between the second and sixth weeks after treatment initiation. The initial prescribed dose is 7.5 mg, administered orally once weekly. If no notable difference occurs in the first month of MTX treatment, the dose can be increased to 15 mg once weekly; however, the dose should not exceed 20 to 25 mg/wk. Common MTX side effects include stomach irritation and gastritis. Patients with liver disease should not take MTX because it is known to cause hepatotoxicity with fibrosis and cirrhosis. MTX is a category X medication; therefore, women who are pregnant or wish to become pregnant are not candidates for this treatment option. Monitoring liver function as well as the WBC and platelet counts is an important aspect of prescribing MTX. Other prescribed DMARDs for the treatment of RA include sulfasalazine, leflunomide, antimalarial agents (hydroxychloroquine), minocycline, and tofacitinib.

In addition to these synthetic DMARDs mentioned above, biologic DMARDs are another treatment option for patients with RA. Drugs in this class include abatacept, rituximab, tocilizumab, and the tumor necrosis factor (TNF) inhibitors. TNF inhibitors are pro-inflammatory cytokines often administered to patients whose disease does not respond appropriately to MTX, or to patients with severe disease. The following TNF inhibitors are administered as subcutaneous injections: etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol. The ideal treatment regimen for patients with RA consists of a combination of MTX and a TNF inhibitor. It is well documented that a combination of the two drugs is superior to the use of either drug alone.5 For those who cannot tolerate TNF inhibitors, DMARD triple drug therapy, with MTX, sulfasalzine, and hydroychloroquine, has shown to be efficacious.

Although nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain and reduce inflammation, they do not alter disease progression, nor do they serve to prevent erosive processes. Unfortunately, NSAIDs cannot be used as monotherapy or in conjunction with DMARDs, so their role in the treatment of RA is limited. Low-dose corticosteroids are another treatment option for patients with RA because they have been shown to prevent disease progression and to provide anti-inflammatory effects. Commonly, corticosteroids are used as an adjunct to DMARDs, reducing disease activity until the DMARDs have reached peak performance. However, corticosteroid treatment is of limited use in the long-term treatment of RA because prolonged steroid use is not advised. A taper should be implemented when corticosteroids are discontinued. If one or two joints are particularly bothersome to the patient, intra-articular corticosteroid injections are beneficial in offering symptomatic relief; however, the injections can be given only four times each year and therefore should be used sparingly.5


The outcomes of RA are variable and include remission, fluctuating disease, and progressively worsening disease. A well-documented study regarding the debilitation of RA indicates that 20% to 30% of patients diagnosed with the disease qualify for work disability 2 to 3 years from disease onset. In addition, 15 years from disease onset, 67% of patients are disabled.10 Complete disease remission has been documented but is rare. However, disease remission commonly occurs during pregnancy, though more than 90% of women experience increased arthritic symptoms 3 months postpartum.3 Early pharmacologic treatment greatly improves patients’ quality of life, because certain drugs can arrest joint damage and relieve the signs and symptoms of RA.5

If left untreated, RA can shorten life expectancy. So early, consistent treatment as the standard of care is essential. Studies indicate that the high mortality rates observed in patients with RA are due mainly to cardiovascular disease.5 The management of risk factors with smoking cessation, blood pressure control, a healthy diet, and stress management is paramount in decreasing the prevalence of cardiovascular disease in patients with RA.

Emily Parker, PA-C, is a physician assistant specializing in general and plastic surgery in Columbia, South Carolina, and Alicia Elam, PharmD, is associate admissions director, Physician Assistant Department, Augusta University, Georgia.


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