Knee Injection
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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 intraarticular 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. [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, 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:
Relative contraindications to PRP knee injections include the following:
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.
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.
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. Ultrasonographic 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 wa 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 ultrasonography, 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]
Boon AJ, Smith J, Dahm DL, Sorenson EJ, Larson DR, Fitz-Gibbon PD, et al. Efficacy of intra-articular botulinum toxin type A in painful knee osteoarthritis: a pilot study. PM R. 2010 Apr. 2(4):268-76. [Medline].
Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cuscó X, Garcia-Balletbó M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011 Mar. 131(3):311-7. [Medline].
Sampson S, Reed M, Silvers H, Meng M, Mandelbaum B. Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil. 2010 Dec. 89(12):961-9. [Medline].
Chou CL, Lee SH, Lu SY, Tsai KL, Ho CY, Lai HC. Therapeutic effects of intra-articular botulinum neurotoxin in advanced knee osteoarthritis. J Chin Med Assoc. 2010 Nov. 73(11):573-80. [Medline].
Conti F, Priori R, Chimenti MS, Coari G, Annovazzi A, Valesini G, et al. Successful treatment with intraarticular infliximab for resistant knee monarthritis in a patient with spondylarthropathy: a role for scintigraphy with 99mTc-infliximab. Arthritis Rheum. 2005 Apr. 52(4):1224-6. [Medline].
Hinton R, Moody RL, Davis AW, Thomas SF. Osteoarthritis: diagnosis and therapeutic considerations. Am Fam Physician. 2002 Mar 1. 65(5):841-8. [Medline].
Ward EE, Jacobson JA, Fessell DP, Hayes CW, van Holsbeeck M. Sonographic detection of Baker’s cysts: comparison with MR imaging. AJR Am J Roentgenol. 2001 Feb. 176(2):373-80. [Medline].
Schumacher HR Jr. Aspiration and injection therapies for joints. Arthritis Rheum. 2003 Jun 15. 49(3):413-20. [Medline].
Schumacher HR, Chen LX. Injectable corticosteroids in treatment of arthritis of the knee. Am J Med. 2005 Nov. 118(11):1208-14. [Medline].
Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006 Apr 19. CD005328. [Medline].
Eder L, Chandran V, Ueng J, Bhella S, Lee KA, Rahman P, et al. Predictors of response to intra-articular steroid injection in psoriatic arthritis. Rheumatology (Oxford). 2010 Jul. 49(7):1367-73. [Medline].
McMahon AM, Tattersall R. Diagnosing juvenile idiopathic arthritis. Paediatrics and Child Health. 2011. 21:12:552-557.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep. 62(9):2569-81. [Medline].
Eggebeen AT. Gout: an update. Am Fam Physician. 2007 Sep 15. 76(6):801-8. [Medline].
[Guideline] Ringold S, Weiss PF, Beukelman T, Dewitt EM, Ilowite NT, Kimura Y, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Care Res (Hoboken). 2013 Oct. 65 (10):1551-63. [Medline]. [Full Text].
McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2017 May 16. 317 (19):1967-1975. [Medline].
Briem K, Axe MJ, Snyder-Mackler L. Functional and perceived response to intra-articular hyaluronan injection in patients with knee osteoarthritis: persistence of treatment effects over 5 months. Knee Surg Sports Traumatol Arthrosc. 2009 Jul. 17(7):763-9. [Medline].
Akeda K, An HS, Okuma M, Attawia M, Miyamoto K, Thonar EJ, et al. Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthritis Cartilage. 2006 Dec. 14(12):1272-80. [Medline].
Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, et al. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy. 2011 Nov. 27(11):1490-501. [Medline].
Lockman LE. Practice tips. Knee joint injections and aspirations: the triangle technique. Can Fam Physician. 2006 Nov. 52(11):1403-4. [Medline].
Richette P, Chevalier X, Ea HK, Eymard F, Henrotin Y, Ornetti P, et al. Hyaluronan for knee osteoarthritis: an updated meta-analysis of trials with low risk of bias. RMD Open. 2015. 1 (1):e000071. [Medline].
Jüni P, Hari R, Rutjes AW, Fischer R, Silletta MG, Reichenbach S, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database Syst Rev. 2015 Oct 22. 10:CD005328. [Medline].
Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD. Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review. Arthroscopy. 2016 Mar. 32 (3):495-505. [Medline].
Filardo G, Kon E, Pereira Ruiz MT, Vaccaro F, Guitaldi R, Di Martino A, et al. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012 Oct. 20 (10):2082-91. [Medline].
Mazzocca AD, McCarthy MB, Chowaniec DM, Cote MP, Romeo AA, Bradley JP, et al. Platelet-rich plasma differs according to preparation method and human variability. J Bone Joint Surg Am. 2012 Feb 15. 94(4):308-16. [Medline].
Rifat SF, Moeller JL. Site-specific techniques of joint injection. Useful additions to your treatment repertoire. Postgrad Med. 2001 Mar. 109(3):123-6, 129-30, 135-6. [Medline].
Rifat SF, Moeller JL. Basics of joint injection. General techniques and tips for safe, effective use. Postgrad Med. 2001 Jan. 109(1):157-60, 165-6. [Medline].
McNeil JD. Intra-articular hyaluronic acid preparations for use in the treatment of osteoarthritis. Int J Evid Based Healthc. 2011 Sep. 9(3):261-4. [Medline].
Agent
Relative Anti-inflammatory Potency
Relative Mineralocorticoid Potency
Solubility
Hydrocortisone
1
2-3
High
Prednisolone
4
1
Medium
Methylprednisolone
5
0
Medium
Triamcinolone
5
0
Medium
Betamethasone
20-30
0
Low
Dexamethasone
20-30
0
Low
Quan Dang Le, MD Pain Fellow, Louisiana State University School of Medicine in New Orleans; Former Clinical Assistant Professor, Department of Medicine, Section of Physical Medicine and Rehabilitation, Louisiana State University School of Medicine in New Orleans
Quan Dang Le, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.
Stephen Kishner, MD, MHA Professor of Clinical Medicine, Physical Medicine and Rehabilitation Residency Program Director, Louisiana State University School of Medicine in New Orleans
Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.
Christian D Clasby, MD Resident Physician, Department of Physician Medicine and Rehabilitation, Louisiana State University School of Medicine in New Orleans
Disclosure: Nothing to disclose.
Navneet Sharma, MD Physician, Department of Physical Medicine and Rehabilitation, Louisiana State University School of Medicine in New Orleans
Navneet Sharma, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, Louisiana State Medical Society
Disclosure: Nothing to disclose.
Thomas M DeBerardino, MD Orthopedic Surgeon, The San Antonio Orthopaedic Group; Professor of Orthopedic Surgery, Baylor College of Medicine as Co-Director, Combined Baylor College of Medicine-The San Antonio Orthopaedic Group, Texas Sports Medicine Fellowship; Medical Director, Burkhart Research Institute for Orthopaedics (BRIO) of the San Antonio Orthopaedic Group; Consulting Surgeon, Sports Medicine, Arthroscopy and Reconstruction of the Knee, Hip and Shoulder
Thomas M DeBerardino, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, Herodicus Society, International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Arthrex, Inc.; MTF; Aesculap; The Foundry, Cotera; ABMT; Conmed; <br/>Received research grant from: Histogenics; Cotera; Arthrex.
Knee Injection
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