Knee Injection

Knee pain and stiffness can be debilitating and difficult to treat. Lifestyle-limiting knee conditions may negatively affect body image and emotional well-being. Weight management, exercises/strengthening programs, physical therapy, physical modalities, orthotics, medications, intra-articular knee injections, and surgery are some of the approaches used to treat knee pain. The most common type of intra-articular knee injection is with corticosteroids, but other agents have been used, including infliximab, hyaluronic acid, botulinum neurotoxin, and platelet-rich plasma (PRP). ^{[1, 2, 3, 4, 5]}

Knee pain can be broadly categorized. It can result from an intra-articular process such as a ligamentous or meniscal injury or fracture. Knee pain can also result from cartilage loss due to osteoarthritis or synovitis. Tendinopathies and bursitis can cause knee pain, along with inflammatory insults such as inflammatory arthritis or septic arthritis. Knee pain can be caused by patellar malalignment or dysfunction and referred pain from other areas, such as the spine or hip.

Knee osteoarthritis can be diagnosed on the basis of clinical presentation and radiographic signs. ^[6]  Baker cysts can be diagnosed on the basis of clinical history and examination and confirmed with ultrasonography (US). ^[7] A clinical presentation consistent with osteoarthritis includes knee joint pain (typically symmetric bilaterally) and morning joint stiffness that resolves within 30-60 minutes and worsens with weightbearing. Physical examination signs include bony joint enlargement, crepitus and pain upon motion, and limited range of motion. Radiographic signs of osteoarthritis include joint-space narrowing, osteophyte formation, subchondral pseudocysts, and increased subchondral bone density. ^[6]

Indications for the various agents used for knee injections are discussed below.

Steroid injections have been shown to relieve pain and inflammation in individuals with osteoarthritis (including osteoarthritis complicated by Baker cysts), juvenile idiopathic arthritis, psoriatic arthritis, acute monoarticular gout, pseudogout, and rheumatoid arthritic knees. ^{[6, 7, 8, 9, 10, 11, 12, 13, 14, 15]}  However, a 2017 randomized study found intra-articular triamcinolone to be less effective for pain relief in this setting than previous studies had. ^[16]

Intra-articular infliximab can be used to treat refractory knee monoarthritis/synovitis in patients with rheumatoid arthritis, Behçet disease, and spondyloarthropathy (eg, ankylosing spondylitis) that is resistant to systemic treatment. ^[5]

Intra-articular knee injections of hyaluronic acid have been shown to provide functional and perceived benefits in knee osteoarthritis for up to 5-6 months. ^[17] Such injections have also been shown to be helpful in patient with knees that are both rheumatoid arthritic and osteoarthritic.

Intra-articular hyaluronic acid injection into a rheumatoid arthritic knee can modulate inflammatory changes, though the exact mechanism or mechanisms are unclear. In knee osteoarthritis, hyaluronic acid can ameliorate the activities of proinflammatory mediators and pain-producing neuropeptides released by activated synovial cells. Hyaluronic acid may work by affecting the number and distribution of the lining synovial cells to trigger reparative processes of osteoarthritis. Hyaluronic acid may help reduce pain in knee osteoarthritis by decreasing the ongoing nerve activities at rest and with movement, thereby modulating nerve impulses and sensitivities. ^[4]

Intra-articular injection of botulinum neurotoxin A into the knee joint may provide therapeutic pain relief in patients with advanced knee osteoarthritis. The mechanism of pain reduction via botulinum neurotoxin A may be neurotransmitter-mediated inhibition of sensory neurons, rather than via neuromuscular junction blockade. According to a preliminary study, pain and stiffness significantly improved and lasted about 3 months following intra-articular knee joint botulinum toxin A injection, though physical function did not significantly improve based on the Western Ontario McMaster Universities Osteoarthritis Index. ^[4]

Intra-articular knee injections of homologous platelet-rich plasma (PRP) have been shown to improve function and quality of life in patients with degenerative lesions of the knee cartilage and osteoarthritis at 6 months post injection. ^[2]  Chondrocytes treated with autologous plasma rich in growth factors (PRGF) have shown a significant increase in proteoglycan and collagen synthesis. ^[18] Additionally, PRP injections have shown greater and longer efficacy than hyaluronic acid injections in reducing pain and symptoms and improved articular function. ^[19]

Intra-articular steroid knee injections are contraindicated in patients with bacteremia, sepsis, periarticular or intra-articular infections (eg, septic arthritis, periarticular cellulitis, and osteomyelitis), significant skin breakdown at the target site, known hypersensitivity to the steroid injection, intraarticular or osteochondral fracture at the target site, severe joint destruction, joint prosthesis, or uncontrolled coagulopathy. ^{[20, 9, 8]}

Absolute contraindications for PRP knee injections include the following:

• Critical thrombocytopenia
• Hemodynamic instability or septicemia
• Septic arthritis, overlying cellulitis, or adjacent osteomyelitis
• Platelet dysfunction syndrome

Relative contraindications to PRP knee injections include the following:

• Regular nonsteroidal anti-inflammatory drug (NSAID) use within 48 hours of the procedure
• Corticosteroid injection of the knee within 1 month or systemic corticosteroid use within 2 weeks
• Recent fever or illness
• Cancer, particularly of bone or blood
• Anemia, with a hemoglobin level lower than 10 g/dL
• Thrombocytopenia, with a platelet count lower than 10 ⁵/μL

Anatomy

The knee is a large complex articulating joint that is highly susceptible to injury. The knee joint consists of three main compartments: medial tibiofemoral, lateral tibiofemoral, and patellofemoral. These share a common synovial cavity. The space between the bones is occupied by the meniscal cartilage, and together they are covered by the synovial membrane and the collateral ligaments.

Procedural planning

A thorough physical evaluation of the knee is imperative for a correct diagnosis and therefore for prescribing a joint injection. Numerous provocative knee tests can be performed to assist in obtaining the correct diagnosis. Plain radiography should also be obtained as part of the diagnostic evaluation. For considerations concerning the various agents used for knee injections, see Indications above and Medication.

Complication prevention

A careful history, physical examination, review of medications and allergies, use of sterile measures, and proper selection of patients, equipment, and medications, along with proper positioning and injection approach, may minimize complications. Care should be taken to avoid injecting too much volume into the knee joint. US or fluoroscopic guidance may be used to improve the accuracy of injection into the knee joint.

In a systematic review and meta-analysis of high-quality randomized controlled trials with a low risk of bias, Richette et al found that intra-articular hyaluronic acid had a moderate but real beneficial effect in patients with knee osteoarthritis. ^[21]

A 2015 Cochrane review assessing the use of intra-articular corticosteroid injections for knee osteoarthritis suggested that the effects of this modality decreased over time and was unable to document remaining effects 6 months after injection. ^[22]

A systematic review by Meheux found that in patients with symptomatic knee osteoarthritis, intra-articular injection of PRP yielded significant clinical improvements for as long as 12 months. ^[23] At 3-12 months post injection, PRP was associated with significantly better clinical outcomes and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores than hyaluronic acid was.

In a 2017 randomized study of 119 patients (average age, 58 years) who had symptomatic knee osteoarthritis with synovitis identified through US, McAlindon et al found that those who underwent quarterly intra-articular injection of 40 mg of triamcinolone experienced significantly greater loss of cartilage volume than those who underwent intra-articular saline injection and that there was no significant difference in knee pain between the two groups. ^[16]