Intra-articular TherapiesIntra-articular therapies are a widely used treatment. As recognized by the original investigators, one of the chief advantages of this treatment modality is that it allows the use of agents that can have systemic toxicity in a very localized manner, thereby preventing (at least in theory) systemic effects. This article will provide a brief overview of the different intra-articular therapies in use today. Actual injection technique will not be discussed, and for this the reader is referred to other sources (Gatter, 1997; Ike, 1997). Indications:
CorticosteroidsThe original reports of intra-articular therapy showed marked improvements in both osteoarthritis and inflammatory arthritis, and today most Rheumatologists frequently use intra-articular steroids. There are seven controlled trials on intra-articular steroids in osteoarthritis, involving a total of 311 patients. The data from these studies do suggest a positive benefit, but one that only lasts 1 - 3 weeks. Patients with joint effusions and local tenderness may have greater benefit. Neither patient function, radiographic features, intra-articular crystals nor a raised synovial fluid cell count predict a good response (Creamer, 1997). At the basic science level, there are a number of mechanisms by which the improvement is thought to occur - mRNA synthesis, B and T cell function, cytokine levels, metalloproteases and synovial permeability (Creamer 1997, Genovese 1998). The optimal dose of steroid has been poorly studied, but it is thought that the volume of injection is of greater importance than the actual amount of steroid. Improvement tends to be greater in joints injected with at least 1 mg/kg compared with those injected with less. Although local anaesthetics such as Lidocaine are often added to the steroid, whether or not this is beneficial has not been studied in osteoarthritis. Given that joint rest leads to decreased steroid leakage, decreased systemic absorption, and better joint tissue repair, many Rheumatologists advise joint rest for 24h post-injection (Ike 1997). The most common agent currently used is methylprednisolone acetate (Depo-Medrol®), but Triacinolone acetonide (Kenalog®) and Triamcinolone hexacetonide (Aristospan®) are also used. These latter two agents have the advantage of greater half life. Commonly, a large joint such as a knee or shoulder would be injected with 40 mg (1 mL) of the methylprednisolone acetate solution. The most common adverse reaction with steroid injections is the post-injection flare, which is related to a steroid-crystal synovitis. The flare is often very painful, but it usually lasts <12 hours, and may be treated with analgesics and ice. Synovial fluid analysis will reveal increased neutrophils and intracellular steroids crystals (these crystals will be irregularly shaped). The most feared complication of steroid injection is septic arthritis. This is a rare complication, and occurs in as few as 1/21,000 injections (Seror et al., 1999) although the rate may be higher in rheumatoid arthritis patients (Gatter 1997). It can occur up to 3 months after injection. Although osteonecrosis is often cited as a possible complication of intra-articular steroid injection, this is somewhat controversial, with some investigators suggesting that there is no association (McCarty et al., 1991). Skin atrophy post-injection can occur when corticosteroid leaks out of the joint space, or where steroid is actually deposited extra-articularly (over 30% of knee injections can be shown to be extra-articular). Cartilage damage can occur directly from trauma by the needle, but also secondary due to the steroid itself. Therefore, it is currently recommended that weight-bearing joints not be injected more than every 3-4 months (Ike 1997) The final point to bear in mind regarding steroid injections is that the effect is not purely on the joint itself - depending on the joint and technique, a variable amount of steroid is absorbed systemically, producing effects at other joints, but also exposing patients to side effects of systemic steroids. PediatricsThe first study on intra-articular steroid use in children was not published until 1984. Studies suggest that in association with serial casting, intra-articular steroids may help reduce flexion contractures about the knee, and produce a prolonged benefit. The benefit may be greater with juvenile rheumatoid arthritis compared with other forms of inflammatory arthritis. Studies also suggest better responses with younger patients, boys, and flexion contractures (Padeh and Passwell 1998). Conscious sedation, Amatopp cream or EMLA cream are often recommended in this population. Triamcinolone hexatonide is more efficacious than betamethasone in two studies, but questions of dose, steroid volume, and joint rest post-injection remain unanswered. Complications are the same as for adults, and subcutaneous atrophy may occur in up to 3% of children.Hyaluronic acidHyaluronic acid is a normal byprooduct of synovial cells which help lubricate and protect the joint. In osteoarthritis, hyaluronic acid may be reduced in both concentration and distribution. This, the theory of viscosupplementation of osteoarthritis - injection of a non-immunogenic, nutrient permeable agent into affected joints may be a disease modifying agent. Present data suggest that the theory is not entirely valid. There is no evidence that intra-articular injections in humans are chonroprotective. Hyaluronic acid likely plays a smaller role than originally thought in joint lubrication (the fact that cartilage-on-cartilage has a very low coefficient of friction to start with, and water that is released from cartilage under pressure further decreasing the coefficient of friction is likely more important). Whether or not hyaluronic acid products change the actual course of osteoarthritis is unknown. Double blind placebo-controlled studies have, however, shown a significant benefit in terms of pain control (Cohen 1998). In some patients, the effect seems to persist for several months, and is not associated with systemic effects. Currently Hyalan G-F 20 (Synvisc®) is a hyaluronic acid product available in Canada. It is produced from rooster combs, and is absolutely contraindicated in persons with allergies to eggs, avian products, and feathers. It is given as a 2 mL injection weekly for 3 weeks. It is not covered by OHIP or MSI, but thecompany will reimburse patients most of the $360 if the patient notes absolutely no benefit. Joint lavageAlthough osteoarthritis is classically thought of as a non-inflammatory degenerative process, there is some evidence of at least mild inflammation. Intra-articular debris (primarily cartilage) is foundint he joint, and can produce a synovitis. Intra-articular adhesions and capsular fibrosis may also occur. Finally, we know that intra-articular degradative enzymes and cytokines are slightly elevated. Intra-articular lavage in osteoarthritic joints removes the debris, disrupts the adhesions and fibrosis and removes (at least temporarily) the degradative ezymes and chemicals. In a single-blind randomized trial, tidal irrigation of the knee joint had significantly decreased stiffness and pain. The procedure is done on an outpatient basis, under local anaesthetic and patients are ambulatory immediately following the procedure (Ike et al., 1992). Although the studies are not double-blinded and the populations may have been highly selected, this raid, easily performed, well-tolerated, low-tech procedure is intriguing. Further study is needed to help define its role.RadioisotopesRadiosynovectomy (the injection of a radioisotope into the joint) has been used around the world for treatment-resistant synovitis, and a possible alternative to surgical synovectomy. The ideal radioisotope has a short half-life and relatively low tissue penetrance. The major concerns are related to leakage of the compound, which can result in radionecrosis of soft tissue around the joint (sometimes requiring surgical debridement), and lymphocyte chromosomal abnormalities. The availability and working conditions for these agents is highly restricted, but radioisotopes likely still have a role to play in patients with inflammatory monoarthritis who have failed other treatments and are poor surgical candidates. When considering this modality, a Rheumatologist experienced in its use should be consulted. Future DirectionsFuture studies will help clarify the role for intra-articular morphine, local anaesthetics and steroids in certain orthopedic surgery settings (Rasmussen et al., 1998). Other investigators are investigating the role of glycosaminoglycans, antibiotics and immunomodulators injected into joints. - R. Joshi & T.E. Towheed Thanks to Dr. Evelyn Sutton, Consultant in Rheumatology, Queen Elizabeth 2 Health Science Centre in Halifax, NS for reviewing the draft copy of this article. References:
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