Pediatric emergency medicine trisk 2988 2988
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inadequately to NSAIDs, so-called disease-modifying antirheumatic drugs (DMARDs)
must be added to control symptoms and prevent long-term complications of the
arthritis. Several agents are available, including sulfasalazine, hydroxychloroquine,
leflunomide, and methotrexate ( Table 101.13 ). Practitioners choose among these
agents based on a child’s age, the severity of the synovitis, and the subtype of arthritis.
Methotrexate is the most commonly used second-line agent and the first shown to
prevent erosive changes. Even at the lower doses used for JIA, methotrexate is
immunosuppressive and can be associated with bone marrow and hepatic toxicity.
Leflunomide inhibits de novo pyrimidine synthesis, especially in activated
lymphocytes. The side effects of leflunomide are similar to those of methotrexate and
the two agents may be used together. Sulfasalazine is most often used in children with
inflammatory bowel disease and spondyloarthropathies (including ERA and psoriatic
arthritis), but it also has a role in milder cases of JIA.
The newest agents in the arthritis armamentarium are the biologic response
modifiers, or biologics, which are medications that specifically target specific
mediators in the inflammatory cascade, like inflammatory cytokines, cellular receptors,
and adhesion molecules. Although they target specific pathways, they are generally
more immunosuppressive than conventional DMARDs. The most widely used biologic
agents are TNF inhibitors. In addition, agents that block specific proinflammatory
cytokines, like anakinra (anti–IL-1R antagonist) and tocilizumab (anti–IL-6
monoclonal antibody) may be used. More recently, agents that target signaling
pathways, for example, Janus kinase inhibitors like tofacitinib, have shown promise in
the treatment of inflammatory arthritis but are currently approved only for use in
adults.
