A 48-year-old man presents with complaints of bilateral morning stiffness in his wrists and knees and pain in these joints on exercise. On physical examination, the joints are slightly swollen. The rest of the examination is unremarkable. His laboratory findings are also negative except for slight anemia, elevated erythrocyte sedimentation rate, and positive rheumatoid factor. With the diagnosis of rheumatoid arthritis, he is started on a regimen of naproxen, 220 mg twice daily (bid). After 1 week, the dosage is increased to 440 mg bid. His symptoms are reduced at this dosage, but he complains of significant heartburn that is not controlled by antacids. He is then switched to celecoxib, 200 mg bid, and on this regimen his joint symptoms and heartburn resolve. Two years later, he returns with increased joint symptoms. His hands, wrists, elbows, feet, and knees are all now involved and appear swollen, warm, and tender. He is given oral methotrexate weekly and his disease decreases by about 20%, but he continues to have multiple tender and swollen joints and morning stiffness that lasts 2 hours. What therapeutic options should be considered at this time? What are the possible complications?
|AS ||Ankylosing spondylitis |
|COX ||Cyclooxygenase |
|DMARD ||Disease-modifying antirheumatic drug |
|GPA ||Granulomatous polyangiitis |
|IL ||Interleukin |
|JIA ||Juvenile idiopathic arthritis |
|NSAID ||Nonsteroidal anti-inflammatory drug |
|OA ||Osteoarthritis |
|PsA ||Psoriatic arthritis |
|PJIA ||Polyarticular juvenile idiopathic arthritis |
|RA ||Rheumatoid arthritis |
|SJIA ||Systemic juvenile idiopathic arthritis |
|SLE ||Systemic lupus erythematosus |
|SSC ||Systemic sclerosis |
|TNF ||Tumor necrosis factor |
The immune response occurs when immunologically competent cells are activated in response to foreign organisms or antigenic substances liberated during the acute or chronic inflammatory response. The chronic inflammation involves the release of eicosanoids, lipoxygenases, leukotrienes, multiple cytokines and chemokines, and a very complex interplay of immunoactive cells including eosinophils, neutrophils, dendritic cells, lymphocytes and their subsets, and macrophages. These are further elucidated in Chapters 18 and 55.
The whole range of autoimmune diseases (eg, RA, vasculitis, SLE) and inflammatory conditions (eg, gout) derive from abnormalities in this cascade.
The cell damage associated with inflammation acts on cell membranes to release leukocyte lysosomal enzymes; arachidonic acid is then liberated from precursor compounds, and various eicosanoids are synthesized (see Chapter 18). The lipoxygenase pathway of arachidonate metabolism yields leukotrienes, which have a powerful chemotactic effect on eosinophils, neutrophils, and macrophages and promote bronchoconstriction and alterations in vascular permeability. During inflammation, stimulation of the neutrophil membranes produces oxygen-derived free radicals and other reactive molecules such as hydrogen peroxide and hydroxyl radicals. The interaction of these substances with arachidonic acid results in the generation of chemotactic substances, thus perpetuating the inflammatory process.
The treatment of patients with inflammation involves two primary goals: first, ...