A risk-benefit assessment of injections of hyaluronan and its derivatives in the treatment of osteoarthritis of the knee.

Hyaluronan is critical for the homeostasis of the joint as an organ, in part, because it provides the rheological properties (viscosity and elasticity) of the synovial fluid. These properties depend upon both the concentration and the molecular weight of the hyaluronan in the synovial fluid. In osteoarthritis, the hyaluronan is both smaller in size and lower in concentration. Thus, it is rational and physiologically meaningful to treat osteoarthritis with viscosupplementation, i.e. injection of material designed to increase the rheological properties of the synovial fluid. It is important, though, to assess the risks and benefits of such a physiological treatment. There are various products on the market for viscosupplementation. These include hyaluronan preparations of relatively low molecular weight (Hyalgan and ARTZ), a hyaluronan preparation of intermediate molecular weight, but still lower molecular weight than that of the hyaluronan in normal healthy synovial fluid (Orthovisc), and a cross-linked hyaluronan (a hylan) of high molecular weight (Synvisc). The evidence from in vitro and in vivo models of osteoarthritis and from clinical trials to date suggests that efficacy, as would be expected by mechanistic reasoning, depends strongly upon molecular weight. The available evidence indicates that these products differ little in the incidence and severity of adverse events (about 2 to 4%, almost always local swelling, and with no adverse sequelae). All are very well tolerated in comparison to nonsteroidal anti-inflammatory drug therapy, although direct comparisons are few. The only potentially serious adverse event is joint infection, which is rare and directly dependent upon the number of injections, among other factors. No infection has been related to contamination of any of the products. In summary, treatment with low molecular weight preparations of hyaluronan seems to be effective. However, viscosupplementation with hyaluronan preparations may have slightly higher risk and less benefit than viscosupplementation with hylans, because the relatively lower molecular weight hyaluronan preparations require more injections which may incur higher costs and theoretically an increased chance of infection. Viscosupplementation with hylans is clearly effective, and the available evidence suggests that the benefits almost certainly outweigh the risks.

Cricoarytenoiditis: CT assessment in rheumatoid arthritis.

The cricoarytenoid (CA) joint is a true diarthrodial joint that can be affected by rheumatoid disease. Its strategic location in the airway anatomy makes its evaluation of clinical importance. Direct fiberoptic laryngoscopy (DFL) and high-resolution computerized tomography (HRCT) were used to assess the larynx in 32 rheumatoid patients. Abnormalities were seen in 75% of patients at endoscopic examination. HRCT studies showed abnormalities in 72%. Erosion-luxation of the CA joint and surrounding soft-tissue swelling can be demonstrated on HRCT scans. A radiologic grading of the rheumatoid larynx is proposed, stressing that accurate evaluation of the larynx should be part of the diagnostic evaluation of every rheumatoid arthritic patient, given the high frequency of occurrence of rheumatoid laryngitis.

Long-term clinical assessment of naproxen on rheumatoid arthritis patients and 51-Cr gastrointestinal bleeding on volunteers.

64 patients with rheumatoid arthritis (R.A.) entered the trial: 40 of them still remain on medication; 28 have so far completed 2 years; 23, 3 years; 12, 4 years using D-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) as the principal anti-inflammatory agent. Tolerance has been good: side effects or complaints, when reported, were mild and transient in nature. Close monitoring of a range of biochemical values by sequential laboratory studies has not revealed naproxen to have many adverse effects. After two years of daily continuous naproxen administration, 19 volunteer patients were subjected to a short-term double-blind cross-over placebo experiment. The results were in favor of a continued therapeutic efficacy of naproxen. The possible gastrointestinal bleeding found in the majority of anti-inflammatory drugs has been studied on 12 volunteers using 51-Cr. Naproxen exhibited a mean G.I. blood loss comparable to placebo or to physiological blood loss in normal volunteers. The conclusion drawn is that naproxen shows a good therapeutic index.