Drug Topics - March 2009 - (Page 42) Continuing Education RHEUMATOID ARTHRITIS ibuprofen that “does not seem to be doing the trick anymore.” Her current state of health has affected her work performance, and she is afraid she is going to lose her job. Jessica does not understand what is happening to her, because her RA has been controlled “ever since I was diagnosed two years ago and put on the right medications.” In addition to her current complaint, Jessica’s only other health condition is epilepsy. Her other medications include a multivitamin once daily, Depakote ER 500 mg three times daily, and Yasmin one tablet daily. She has no known drug allergies. Her 64-year-old mother has hypertension, type 2 diabetes mellitus, dyslipidemia, osteoporosis, and RA. Her father died at age 61 in an auto accident. Upon physical examination today, her physician finds bilateral swelling and warmth of the right and left metacarpophalangeal and proximal interphalangeal joints, elbows, and wrists. In addition, a rheumatoid nodule was noted on her left elbow. Labs drawn today are within normal limits, except for an elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF). In light of her clinical presentation and findings, Jessica’s physician asks you, the clinical pharmacist, what treatment strategies should be considered. The physician wonders whether infliximab should be started, since Jessica’s mother is being successfully treated with it. How do you respond? with enzymes. Uninhibited growth of this pannus leads to invasion of the joint space and cartilage, eventually causing bony erosions and ultimately, joint destruction. Activation of the immune system involves both cellular and humoral immune responses. During the cellular immune response, HLA-DR4 and other antigen-presenting cells interact with CD4 cells, yielding a resultant secretion of interleukin-2 (IL-2). This biological response modifier binds IL-2 receptors to B cells, components of the humoral immune response. As a result, the B cells are responsible for the production of antibodies, namely rheumatoid factor (RF). RF activates polymorphonuclear cells (PMNs) and causes the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and IL-1. These agents are responsible for secreting enzymes known as metalloproteinases that cause joint and cartilage destruction. This process continues as more and more cells are recruited to the area of destruction, a process known as chemotaxis, to further exacerbate the inflammation. This cascade of events presents many potential therapeutic targets, especially for the newer, biologic agents that will be discussed in this article. Background Rheumatoid arthritis is a chronic inflammatory autoimmune disorder characterized by symmetrical joint involvement and sometimes extra-articular manifestations. Approximately 0.5 percent to 1.5 percent of the adult population is affected by this progressive disease, which occurs two to three times more frequently in women than in men and spans all racial and ethnic groups. RA generally presents in patients between 30 and 60 years old, with an increased incidence through age 85, though it may occur at any age. If left untreated, this disease can eventually cause joint deformity, disability, and possibly premature death. The exact etiology of RA is unknown. However, genetics are believed to play a role in its development. The presence of alleles such as HLA-DR1, HLA-DR4, HLA-DR6, and HLADR10 has been implicated with RA. Once the patient has been exposed to potential environmental triggers such as cigarette smoke, heavy-metal toxicities, food allergens, viruses, and bacteria, development of preclinical autoimmunity occurs and eventually symptoms will begin to emerge. Pathophysiology Though its etiology is not completely known, RA is an autoimmune disorder in which the body is unable to distinguish between itself and foreign tissue. As a result, the body begins to attack its joints. Each of our joints is lined with a membrane known as the synovium, which is responsible for lubricating the joint. In RA, this synovial lining becomes inflamed. Chronic inflammation eventually leads to the development of a pannus, a highly inflamed, highly erosive exudate that is packed Clinical presentation / Diagnostic criteria Most patients will experience a slow onset of symptoms over a period of weeks to months. In addition, some patients may experience a prodromal phase in which they may report fatigue, anorexia, and malaise. About 15 percent of patients will have an acute onset over a period of days to weeks, and between 8 percent and 15 percent of patients will develop symptoms after an event such as an illness. Hallmark findings in RA include painful, swollen, and tender joints, with symmetrical involvement. Commonly affected joints include the hands, feet, wrists, knees, and elbows. However, RA is a systemic disease and can affect areas outside the joints. Eight to 12 percent of patients develop these extra-articular disease manifestations, which are associated with increased morbidity and mortality. Rheumatoid nodules represent one such extra-articular manifestation. These are subcutaneous growths commonly found on extensor surfaces such as elbows and forearms. They are typically asymptomatic and may occur in deeper tissues and organs like the lungs. Nodules may result from progressive disease or from medications used to treat RA, such as methotrexate. Other extra-articular manifestations, such as cardiovascular disease, vasculitis, interstitial lung disease, ocular complications (e.g., scleritis, episcleritis, Sjögren’s disease), Felty’s syndrome, and anemia may occur. While no single test can be performed to rule RA in or out, several laboratory markers and tests can be helpful. Both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are useful markers of inflammation typically elevated in patients with RA. They are not specific for the condition but may be used to monitor disease progression. In addition, rheumatoid factor levels should be assessed. The W W W.D R U GTO P I C S .C O M 42 DRUG TOPICS March 2009 http://WWW.DRUGTOPICS.COM
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