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Indications and Contraindications, Effects and SideEffects of ultrasound-guided steroid injections Poster No.: C-1582 Congress: ECR 2015 Type: Educational Exhibit Authors: E. A. Dick, A. Kindelerer, I. Anwar, A. K. Lim; London/UK Keywords: Drugs / Reactions, Biological effects, Treatment effects, Complications, Ultrasound, Musculoskeletal soft tissue, Musculoskeletal joint DOI: 10.1594/ecr2015/C-1582 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myESR.org Page 1 of 12 Learning objectives To understand the indications for steroid injections of the joints and soft tissues. To be aware of interactions of other medications and steroids. To understand the potential adverse effects of steroid injections, and which preparations have greater or lesser risk of these. Background Radiologists are increasingly asked to perform Ultrasound guided injections of steroids into or around the joints or tendons of patients to provide symptomatic relief from arthropathy, bursitis and tendonitis. Injectable corticosteroids have been used to treat arthritic joints for over 50 years (1). However there are few controlled trials and much of the evidence on safety and efficacy of steroids is anecdotal. All steroids potentially interact with other medications. Before steroid administration a drug history should be taken and the patient counselled taking into account the information presented in this poster: Interactions with other medication 1. Blood thinning agents - including Aspirin & Warfarin. The National Institute for Clinical Excellence (NICE) recommends that caution is used if the patient is taking anti-coagulant medication (2). The increased risk of bleeding and bruising should be explained and appropriate measures (increased compression time) taken if required. 2. Diabetic medication. Page 2 of 12 Blood sugar levels will rise slightly after steroid injections of soft tissues for 1 to 21 days (3, 4). However in a study of hand and wrist extraarticular injections, these elevated levels are generally not clinically significant (4). Intraarticular injections have little effect on blood sugar. 3. Antiretroviral treatment with Ritanovir - a protease inhibitor. Steroid injections are contraindicated in patients on Ritanovir because of the recently recognised risk of adrenal insufficiency: In 2009 two HIV infected patients being treated as part of their highly active anti-retroviral treatment (HAART) developed Cushings Syndrome and adrenal suppression after intraarticular triamcinolone acetate administration. The mechanism is due to increased systemic concentrations of triamcinolone (over 10 x normal levels) due to inhibition of the cytochrome p450 3A4 metabolism. The symptoms of Cushings developed two weeks after the injection. In both patients, the secondary adrenal insufficiency settled with conservative management. (5). After this initial case report a retrospective study of 171 HIV infected patients who received one or more corticosteroid injections was conducted. Nine patients developed biochemical adrenal insufficiency of whom five had Cushings Syndrome. All patients who developed adrenal insufficiency were on Protease Inhibitors. The risk was greater with more than one injection within a six month period (6). The most recent advice is that 11% of patients on Protease Inhibitors who need steroid injections develop adrenal insufficiency and therefore steroid injections should only be used with great caution and close monitoring (6). Who, where, why to inject? Who: 1. Seropositive and seronegative inflammatory arthritides 2. Crystal arthritides (gout and pseudogout) (1). 3. Osteoarthritis - intraarticular injections (2, 7). Where: 1 Intra or periarticular. 2 Soft tissue - bursa, tendon sheaths, around nerves (such as the carpal tunnel) or into or around tendon insertions (eg common extensor epicondyltis at the elbow) (3). Page 3 of 12 Why: The therapeutic aim may be complete and permanent cure of pain, or providing a pain free window , which may be used for rehabilitation, with the expectation of a repeated injection for future pain relief (3). Improved muscle strength and range of movement may also be achieved (1). How Often to Inject? NICE recommends that no joint should be injected more than three times a year in Osteoarthritis. The American College of Rheumatology advises against repeated and numerous injections in the same joint. (8) Absolute Contraindications: These include injection into a prosthetic joint, injection at a site of possible infection or through a site of possible infection. Injection of a fracture is contra-indicated (2) Which anatomical site is there good evidence for efficacy of corticosteroid injection? De Quervains tenosynovitis: Considered the preferred initial treatment (9). 90% of patients responded to a single intra-tendon sheath steroid injection (10). Trigger finger: Two randomized controlled studies have shown single corticosteroid injections of methylprednisolone or betamethasone was successful in 60% (compared with 20% for local anaesthetic alone) (11). Carpal Tunnel Syndrome: Good evidence that it is effective (1) Lateral epicondylitis: Good evidence for short term pain relief (12) Subacromial bursitis: Good evidence for short term pain relief. A study of patients from the Hospital for Joint Diseases, New York, compared patients who received triamcinolone nad lidocaine with those who received lidocaine alone into the subacromial bursa. At a mean of 30 weeks post injection the steroid group showed benefit in reducing pain and increasing range of movement (13). Greater trochanteric pain syndrome: Effective treatment in the short term (one week) in 77% (1, 14) Page 4 of 12 Knee: Intraarticular corticosteroid can reduce pain and increase range of movement in patients with osteoarthritis for up to3-4 weeks. (7). Which steroids should be used? There are a variety of injectable steroids available, with variable solubility, length of effect and adverse effects. Preparations: Depot formulation remain at the injected site for a long time and display local effects. Commonly used depot formulations include: methylprednisolone acetate, triamcinolone acetonide, triamcinolone hexacetonide and hydrocortisone acetate. Solubility: Solubility is important. Triamcinolone hexacetonide and triamcinolone acetonide (Kenalog) are the least soluble. Methylpredinosolone acetate (depomedrone) and hydrocortisone are more soluble (3). Insoluble steroids maintain synovial levels for longer, have less systemic effects but a higher incident of cutaneous side effects (3). Some data suggests low solubility correlates with a more sustained effect, but others suggest the opposite (1, 15). Low solubility compounds are well suited for intra-articular injections but may not be so well suited to soft tissue injections. A Survey of American Rheumatologists found that choice of corticosteroid varied with geographical location of training of the Rheumatologist. Only triamcinolone hexacetonide was chosen primarily for efficacy (16). NICE guidelines are that in Osteoarthritis small joints should be injected with methylprednisolone or hydrocortisone and large joints should be injected with methylprednisolone or triamcinolone acetonide (2). Local Anaesthetic: Additional local anaesthetic helps to differentiate local from referred pain. Page 5 of 12 If mixed with local anaesthetic, careful inspection of the mixture to exclude flocculation is required prior to injection (1). Mechanism of Action: Injectable depot corticosteroids have a Local Action: -reduce inflammation in synovial tissues -reduce oedema -reduce number of lymphocytes, macrophages and mast cells -reduce number of inflammatory cells within a joint in the long term (1) Systemic Effects: (Dose related) -lower Erythrocyte Sedimentation Rate -lower C Reactive Protein -may cause less inflammation in non-injected joints (1) Effect on Articular Cartilage: There is debate about whether corticosteroids hasten chondrocyte death in osteoarthritis (17). A study by Raynaud et al is reassuring: 68 patients with knee osteoarthritis received injections of triamcinolone acetonide 40mg or saline every three months for two years. While there was no effect on deterioration of osteoarthritis as judged by joint space loss, those who received steroid did have improvements in the range of movement (18). In Osteoarthritis, degeneration of cartilage is accompanied by decreasing responsiveness of chondrocytes to circulating glucocorticoids, resulting in increased cytokine production. This is theorised to cause more cartilage degradation, therefore intra-articular steroids may arrest this process (18). However, more recently investigations on the effects local anaesthetic agents alone and in combination with corticosteroids has shown that local anaesthetic agents can be chondrotoxic alone or in combination with corticosteroid (17, 19) Page 6 of 12 Ultrasound guided versus Clinically Guided Injections: There is surprisingly little evidence on this. However Naredo et al's landmark paper (20) showed ultrasound guided subacromial injections were significantly better at reducing pain and increasing shoulder function. Aspiration prior to Injection: Successful aspiration of fluid is associated with increased chance of successful response ot steroid and lower likelihood of return of symptoms (21). This may be because the joint is less painful and stiff, or because the corticosteroid is not so diluted. Care after injection: There is contradictory evidence regarding the value of resting a joint after injection. NICE recommends resting for 24 hours. Rheumatologists in the USA vary in their post-injection instructions: 29% do not restrict weight-bearing but 8% restrict weight bearing for 1 week or more (16). The effect of resting may not be apparent in the short term (eg up to 3 weeks post injection) but may be more recognisable towards the end of recovery (24 weeks) (22). Findings and procedure details What should be included in the consent process? In addition to the usual risks of intervention (infection, discomfort, haematoma), radiologists should explain the risks of steroid: 1 'flare' - worsening symptoms for a few days. This is an acute inflammatory reaction/ chemical synovitis due to the microcrystalline suspension. It is thought to occur in 0.1-10% of patients (2, 8) 2 depigmentation, fat atrophy and striae - Cutaneous atrophy has been shown to occur with all corticosteroid preparations (23) but is worse with non-soluble steroid eg triamcinolone preparations and rarer after methylprednisolone or hydrocortisone acetate (24). This also occurs with intra-articular injections when peri-articular leakage of steroid occurs. The risk is greatest with large or repeated doses of long-acting potent steroid (2). Page 7 of 12 Skin atrophy and depigmentation my be reversible after a number of years but striae are usually permanent (24) 3. tendon rupture - theoretically worse with non-soluble steroids. This is rare but has been reported both with intratendinous injection and peritendinous injections (25). 4. Flushing. Occurs in up to 15% of patients, more commonly female, onset within a few hours, effect lasts 3-4 days. (25, 1) Images for this section: Fig. 2: Ultrasound guided needle advancement into 4th MTP joint Page 8 of 12 Fig. 3: (same patient as Fig 2) Needle tip positioned in 4th MTP joint for steroid injection Fig. 1: Ultrasound guided injection of 1st CMC joint Page 9 of 12 Conclusion Steroid injections can interact with other medication and have adverse effects, both of which should be considered and discussed with the patient pre-procedure. Personal information References 1 Cole BJ, Schumacher HR. Injectable corticosteroids in modern practice. J Am Acad Orthop Surg 2005, 13, 37-46. 2 NICE GUIDELINES ON OSTEOARTHRITIS: Feb 2014 th (downloaded 6 Jan 2015) http://www.nice.org.uk/guidance/cg177/chapter/ recommendations#pharmacological-management. 3 Stephens MB, Beutler AI, O'Connor FG. Musculoskeletal Injections: A review of the evidence. Am Fam Physician 2008 78(8) 971-976. 4 Catalano LW, Glickel SZ, Barron OA, Harrison R, Marshall A, Purcelli-Lafer M. Effect of local corticosteroid injection of the hand and wrist on blood glucose in patients with diabetes mellitus. Orthopaedics 2012 35(12) e1754-8. 5 Dort K, Padia S, Wispelwey B, Moore CC. Adrenal Suppression due to an interaction between ritonavir and injected triamcinolone: a case report. AIDS Research and Therapy 2009 6.10-14 6 Hyle EP, Wood BR, Backman ES, Noubary F, Hwang J, Zhigang Lu et al. High Frequency of hypothalamic-pituitary-adrenal axis dysfunction after local corticosteroid injection in HIV-infected patients on protease inhibitor therapy J Acq Im Def Synd 2013 63(5) 602-608. 7 Godwin M, Dawes M. Intra-articular steroid injections for painful knees.Metaanalysis. Can Fam Physician 2004, 50 241-248. 8 American College of Rheumatology Guidelines on Joint Injection/Aspiration. th (downloaded 6 Jan 2015) http://www.rheumatology.org/Practice/Clinical/Patients/ Diseases_And_Conditions/Joint_Injection/Aspiration/ Page 10 of 12 9 Richie CA, Briner WW. Corticosteroid Injection for treatment of de Quervain's Tenosynovitis. J Am Board Fam Pract 2003, 16, 102-106. 10 Anderson BC, Manthey R, Brouns MC. Treatment of De Quervain's tenosynovitis with corticosteroid: a prospective study of the response to local injection. Arthritis Rheum 1991 34, 793-798. 11 Lambert MA, Morton RJ, Sloan JP: Controlled study of the use of local steriod injection in the treatment of trigger finger and thumb. J Hand Surg (Br) 1992, 17, 69-70. 12 Assendelft W, Green S, Buchbinder R, Struijs P, Smidt N. Tennis Elbow: Clinical Review. BMJ 2003, 327, 329-30. 13 Blair, B, Rokito A, Cuomo F, Jarolem K, Zuckerman J. Efficacy of Injections of Corticosteroids for Subacromial Impingment syndrome. JBJS 1996 78(11), 1685-9 14 Labrosse JM, Cardinal E, Leduc BE, Duranceau J, Remillard J, Bureau NJ, Belblidia A, Brassard P. Effectiveness of Ultraosund-guided corticosteroid injection for the treatment of gluteus medius tendinopathy. AJR 2010 194. 202-206. 15 Pyne D, Ioannou Y, Mootoo R, Bhanji A. Intra-articular steroids in knee OA: a comparative study of triamcinolone hexacetonide and methylprednisolone acetate. Clin Rheum 2004 23, 116-120. 16 Centeno LM, Moore. Preferred intraarticular corticosteroids and associated practice: a survey of members of the American College of Rheumatology. Arthritis Care Res. 1994 7(3) 151-5. 17 Syed HM, Green L, Bianski B, Jobe CM, Wongworawat MD. Bupivicaine and Triamcinolone may be toxic to human chondrocytes. Clin Orthop Relat Research 2011, 469, 2941-2947. 18 Raynauld J-P, Buckland-Wright C, Ward R, Choquette D, Haraoui B, Martel-Pelletier J et al. Safety and Efficacy of Long term intra articular steroid injections in OA of the Knee. Arthritis and Rheumatism 2003, 48, 370-377. 19 Breu A, Rosenmeier K, Angele P, Zink W. The cytotoxicity of bupvicaine, ropivacaine and mepivacaine on human chondrocyte and cartilage. Anaesthetic Analgesia. 2013 117(2) 514-22. 20 Naredo E, Cabero F, Beneyoto P. A randomized comparative study of short term response to blind injection versus sonographic-guided injection of local corticosteroids in patients with painful shoulder. J Rheumatol 2004 31,308-314. 21 Weitoft T, Uddenfeldt P. Importanceof synovial fluid aspiration when injecting intraarticular corticosteroids. Ann Rheum Dis 2000, 59, 233-235. Page 11 of 12 22 Chakravarty K, Pharoah PD, Scott DG. A randomized controlled study of post injection rest following intra-articular steroid therapy for knee synovitis. Br J Rheumatolog 1994, 33, 464-468. 23 Cassidy J, Bole GG. Cutaneous Atrophy Secondary to Intra-articular Corticosteroid administration. Ann Int Med 1966 65(5) 1008-1018. 24 Rostron PKM, Calver RF. Subcutaneous atrophy following methylprednisolone injection in Osgood-Schlatter Epiphysitis. JBJS 1979 61-A, 627-628. 25 Gottlieb NL, Riskin WG. Complications of Local Corticosteroid Injections. JAMA 1980 243 1547-1548. Page 12 of 12