Hip and knee IACS practice recommendations from organizations

Indications for IACS and other soft tissue musculoskeletal injections include pain relief and improved function. In 2019, the ACR updated their 2019 recommendations for hip and knee IACS.10 In patients with knee and hip OA, a strong recommendation was made for IACS (table 3). The AAOS updated their advice from ‘unable to recommend (knee)’11 12 to ‘could be considered’ in their most recent version.13 14 The EULAR recommended the injection of a long-acting glucocorticoid for acute exacerbation of knee pain, especially if accompanied by effusion.15 For hip OA, they changed their original advice from ‘not recommended’16 to ‘maybe considered in patients with flare that is unresponsive to analgesic or NSAID.’17 This was prompted by a randomized controlled trial (RCT) that showed better results with IACS compared with local anesthetic alone, and two uncontrolled trials showed some short-term (3 months) pain reduction from IACS injection.17 The Osteoarthritis Research Society International (OARSI)18 conditionally recommended IACS for knee OA, but no pharmacological treatment was conditionally recommended for hip OA, partly because of the lack of hip-specific RCTs.18

General statements and contraindications for IACS

IACS are usually injected with local anesthetic. One study compared local anesthetic with or without methylprednisolone (MP) in patients with lateral epicondylitis.19 The recovery rate, in terms of pain relief and recovery of function, was significantly better in the corticosteroid and local anesthetic group throughout the 12-week follow-up.

The absolute and relative contraindications to intra-articular (IA) and soft tissue CSIs are listed in box 1.

Pharmacokinetic and pharmacodynamic studies of IACS injections

Pharmacokinetic studies were done after knee and glenohumeral joint injections. A pharmacokinetic study after knee IACS27 compared TA with TA extended-release. They showed the median time to achieve peak plasma concentration (T_max) of triamcinolone after TA injection to be 6.5 (range 2, 360) hours and the median terminal half-life (T_1/2) to be 663.8 (range 18, 2067) hours (663 hours=27 days) after knee IACS. Another pharmacokinetic study looked at the triamcinolone levels after knee IACS injection of extended-release TA.28 One study showed maximum synovial fluid concentration at week 1, when the sample was obtained, and maximum plasma levels at 24 hours that declined over weeks 6–12 for synovial fluid and weeks 12–20 for plasma levels.28

Another pharmacokinetic study compared standard TA with an extended-release form after glenohumeral joint IACS.32 Lower peak levels and systemic levels of TA were noted after TA extended-release compared with TA. For TA, the T_max was 4 (1–57 hours) (median, range) and remained very high at 3–5 days after which it declined. The t_(1/2) was 613 (287–1026) hours.32 It should be noted that the plasma levels remained high up to day 15; T_1/2 ranged from 287 (12 days) to 1026 hours (42 days); and duration of measurable plasma levels was 839 hours (35 days).

Regarding pain relief after knee IACS, a study noted relief at 1 week that extended up to their 12-week follow-up, with both immediate-release triamcinolone and extended-release TA.33 The above studies suggest that pain relief from IACS injections can last from a few weeks up to 3 months.

For SRs on corticosteroid pharmacology and AEs in IACS, see box 2.

Accuracy and outcomes of US-guided corticosteroid joint injections

Studies on the accuracy and outcomes of landmark and image-guided injections are discussed in the specific joint sections; studies that involved several joints are discussed here. An RCT compared US with landmark-based injection in the wrist, hand, or ankle of 114 patients with chronic inflammatory arthritis including RA, psoriatic arthritis, or other spondyloarthritis.41 The study showed better short-term outcomes, measured by functional and clinical scores, with the use of US guidance. A separate RCT of 184 patients with similar chronic inflammatory arthritis across shoulder, elbow, wrist, knee, and ankle found that USG injections had higher accuracy but showed similar clinical outcomes.42

A systematic review of 17 studies confirmed greater accuracy of USG IACS, compared with anatomic guidance, into the shoulder, elbow, wrist, hip, knee, or ankle joints and demonstrated better short-term clinical outcomes.43 However, there were no differences in long-term outcome measures with either technique. A recent review noted increased accuracy of USG injections regardless of location, with the exception of the hip (due to a lack of comparative studies).44

For SRs on the role of imaging in IACS, see box 3. Discussions supporting the SRs on the role of imaging are noted in the section on specific joints.

Chronic shoulder joint pain: etiologies

The shoulder joint consists of the primary articulations of the acromioclavicular joint, between the clavicle and the acromion of the scapula; the glenohumeral joint, between the glenoid cavity of the scapula and the humerus; and the scapulothoracic articulation. The etiologies of chronic shoulder pain include acromioclavicular glenohumeral and OA, rotator cuff disorders, adhesive capsulitis (AC), and instability.45

Acromioclavicular osteoarthritis

The clinical presentation of acromioclavicular joint OA includes superior shoulder pain, joint tenderness, and a painful body cross adduction test. In the body cross test, the affected arm is elevated to 90 degrees; pain is reproduced in the acromioclavicular joint when the examiner takes the patient’s elbow and adducts the arm across the body.46 Patients with acromioclavicular OA usually present with gradual pain and loss of motion or a history of dislocation or subluxation.45 Imaging studies are indicated when the diagnosis is not clear. MRI shows degenerative changes in the joint, osteophytes and/or hypertrophy of the clavicle and acromion, and joint edema.47 As noted previously, IACS is recommended when there is no improvement with the initial conservative management.48 Non-surgical management includes suprascapular nerve blocks.49 There has been no dose-response study on IACS for the AC joint, although a dose of 40 mg MP has been injected under fluoroscopy.46

Adhesive capsulitis and glenohumeral joint disease

Disorders of and around the glenohumeral joint are multifactorial, resulting in frequent shoulder pain, with a lifetime prevalence as high as 67%, and significant functional impairment during and long after the initial painful episode.50

AC (‘frozen shoulder’) is a syndrome thought to involve the capsule of the glenohumeral joint, featuring characteristics of shoulder pain, stiffness with reduced range of active and passive motion, and otherwise negative radiographic findings.51 ACs have been proposed to be a fibroproliferative disease52 and may be either idiopathic or associated with trauma, tear, surgery, immobilization, or medical diseases (such as diabetes, stroke, thyroid disorders, or Parkinson’s disease). Treatments include conservative analgesic management, physical therapy (PT), short-wave diathermy, IACS, intracapsular hydrodistension, manipulation under anesthesia, and arthroscopic release.

Glenohumeral instability is caused by trauma, repetitive motion of the shoulder (eg, throwing), high demand shoulder activities (eg, push-ups, bench presses), or loose ligaments leading to chronic shoulder instability. Treatment is conservative48 53; surgery is performed in recalcitrant cases.54

Tendinitis of the long head of the biceps

The long head of the biceps tendon is susceptible to trauma, instability, impingement, inflammation of the tendon sheath, instability, and degeneration, resulting in anterior shoulder pain. Patients with biceps tendinitis or tendinosis complain of a deep, throbbing ache in the anterior shoulder.55 Repetitive overhead motion of the arm initiates or exacerbates the symptoms. A common isolated finding in biceps tendinitis is tenderness over the bicipital groove with the arm in 10 degrees of internal rotation.55 Tests to diagnose tendinitis of the long head of the biceps include the Speed, Yergason, and upper cut tests. These maneuvers are considered positive when pain is elicited in the bicipital groove. A comparison of the tests concluded that the upper cut test should be used as the screening test and the Speed and Yergason tests as confirmatory tests for confirming disorders of the biceps tendon.56 MRI can help differentiate between an isolated tear or inflammation of the biceps tendon and other shoulder pathology.

Similar to other causes of shoulder pain, treatment is conservative: rest, medications, and PT. Patients with tendinitis and tenosynovitis who do not respond to conservative treatment may benefit from USG CSIs into the biceps tendon sheath.

Scapulothoracic bursitis

Symptomatic scapulothoracic disorders include scapulothoracic crepitus and scapulothoracic bursitis, collectively called ‘snapping scapula syndrome.’57 Scapulothoracic crepitus is disruption of the normal gliding of the scapula over the thorax; inflammation of the bursa occurs when there is repetitive movement of the scapula over the thoracic wall (eg, baseball, swimming). Plain X-ray may show osseous lesions while CT or MRI reveal bursitis. Treatment is conservative,58 59 with NSAIDs, activity modification, and rehabilitation. Landmark scapulothoracic bursa injection, between the serratus anterior and the lateral chest wall, has been described.60 61 Surgery includes removal of masses or impinging osseous lesions, bursectomy, or scapulothoracic fusion.57 59 62

IACS and subacromial subdeltoid bursa corticosteroid injection

CSI for shoulder pain can be IA or subacromial (in or around the SASDB). IACS are done for acromioclavicular and glenohumeral joint pain and ACs, while SASDB are usually conducted for subacromial bursitis, rotator cuff disorders, and/or impingement syndrome (figure 1).65

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Figure 1

Injection sites for shoulder pain. A—acromioclavicular joint; B—subacromial subdeltoid bursa; C—long head of the biceps tendon; D—glenohumeral joint. Note that the injection is around the biceps tendon or tendon sheath. Image courtesy of Sebastian Encalada, MD, Mayo Clinic, Jacksonville, Florida.

The location target for CSI (IACS vs SASDB) for treatment of ACs has been studied. Chen et al conducted a meta-analysis of seven articles comparing IACS with SASDB for frozen shoulder and found that IACS reduced pain to a greater degree for up to 3 months compared with SASDB injection.66 A review and a meta-analysis observed no difference between the two approaches and recommended that either approach can be used for ACs.65 67

In an RCT of 58 subjects with moderate-to-severe poststroke shoulder pain and associated rotator cuff or biceps tendon disease, SASDB injection with corticosteroid conferred pain relief and range of motion (ROM) improvement in shoulder flexion for up to 8 weeks compared with lidocaine.68

Acromioclavicular and glenohumeral IACS: image-guided versus landmark guidance

A retrospective study showed that IACS USG injection for the treatment of painful acromioclavicular joint due to OA produced better pain and function outcomes than did landmark-guided IACS at 6 months.69 A 2012 Cochrane review on shoulder IACS that included a meta-analysis of RCTs and non-RCTs showed better pain outcomes at 6 weeks with image-guided (US) over landmark-guided injections in three out of five trials.70 However, the difference was no longer significant when trials with inadequate blinding and allocation concealment were removed.70 A recent double-blind RCT between USG and landmark-guided injections for adhesive capsulitis did not show a difference in pain or functional outcomes despite greater accuracy of the USG injections.71 This was confirmed in another study.37

For glenohumeral joint injections, there have been issues on the accuracy of landmark guidance.72 For this reason, IACS injection into the glenohumeral joint under fluoroscopy was recommended.48 One review showed the US to have improved accuracy over fluoroscopy in glenohumeral joint injections, but it did not reach statistical significance.37 Two other studies noted comparable results in accuracy, pain relief, and functional outcomes between US-guided and fluoroscopy-guided glenohumeral joint injections.38 39

Subacromial subdeltoid bursa corticosteroid injections: landmark approaches

SASDB injections using landmark approaches can be administered via an anterior, lateral, or posterior approaches. An RCT including 50 subjects, which evaluated landmark-based mid-lateral (a variant of the lateral approach) versus the posterior subacromial approach, conferred greater accuracy for mid-lateral approach (92% vs 68%). However, there was no difference in functional clinical outcomes.73 A similar RCT in 80 subjects with subacromial impingement syndrome showed no difference in Shoulder Pain and Disability Index (SPADI), night pain, or shoulder function for up to 12 weeks between posterior versus lateral approaches.74 These results were confirmed in a review of five RCTs and three trials; however, they did not determine superiority of specific approaches in subacromial impingement syndrome.75

US-guided versus landmark injection subacromial subdeltoid bursa corticosteroid injections

SASDB may require less precision in view of its size (largest bursa in the body) and the superficial location of the subacromial space. A study showed similar accuracy between landmark and USG SASDB injections; the injection was located in the bursa in all cases. However, the injections were performed by either an experienced orthopedic surgeon or an experienced musculoskeletal radiologist.36 A study questioned the accuracy of landmark techniques.76 In this study, the investigators noted 76% (13 of 33 patients) accuracy with the posterior approach and 69% (10 of 33) accuracy with the anteromedial approach.76 Most important, only the injection into the SASDB resulted in a significant reduction of pain and an improvement in the functional scores.

Two reviews compared the outcomes of USG versus landmark-based SASDB injection.77 78 Some analyses favored USG based on 4-week outcomes.77 79 A 2015 review of seven papers (445 patients) showed significantly greater improvement in pain and function with USG.77 Such improved efficacy was not shown in a 2020 review of four papers (234 patients).78 Some of the differences were based on study selection, but differences were also due to interpretation of the data. Analyses were complicated by multiple study outcomes (pain, function, ROM, or other global scores), heterogeneity across studies, and greater risk of bias (for the more inclusive meta-analyses). The sample sizes of all the primary RCTs included were small (fewer than 50 subjects per group).

Two other reviews on USG versus landmark injections looked at papers that included both SASDB and IACS. One group noted that while there was a statistically significant improvement, the clinical benefit was questionable and may not represent ‘clinically useful differences’80; the other group showed a benefit for USG.78 Overall, the studies showed that accuracy improved with USG injections, compared with landmark approaches in SASDB and IACS injections.

Dose-response studies after shoulder IACS and SASDB injections

An RCT in 60 patients with full-thickness rotator cuff tears compared a single IACS of TA 40 mg (one vs two vs no injections), 21 days apart.51 Night pain and activity-related pain were improved among the CSI groups at 1 and 3 months. Long-term Constant-Murley shoulder score (a scale that assesses shoulder function based on pain, activities of daily living, strength, and ROM) was similar with treatment versus no treatment at 3–6 months. The two-injection steroid dose provided no benefit over the single-dose injection.

An RCT showed no difference in efficacy, measured by SPADI between 20 mg, 40 mg, and 80 mg TA IACS injected into the glenohumeral joint; all doses showed a reduction of SPADI at the 6-month follow-up.81

There is limited evidence on the use of biologic agents and inconclusive results for hyaluronic acid in glenohumeral joint injections.64

Two RCTs on IACS for adhesive capsulitis and shoulder joint stiffness showed no difference between 20 mg and 40 mg TA.82 83 In one triple-blind placebo-controlled study in patients with adhesive capsulitis, the two doses were noted to be equally effective in terms of SPADI, VAS, and ROM at the shoulder up to the 12-week follow-up of the study.82 Another RCT showed equal efficacy between the two doses in patients with shoulder stiffness.83 Measures included VAS, ROM, and the American Shoulder and Elbow Surgeons score; relief lasted up to the 12-month follow-up.

Another RCT of 79 subjects with primary OA and full-thickness rotator cuff tear compared USG SASDB injection using TA 20 mg vs TA 40 mg vs placebo with follow-up at 8 weeks.84 The SASDB injections improved pain VAS and active ROM for both doses over placebo throughout the study, but no difference between the TA doses.

In another RCT of SASDB for shoulder pain, 62 subjects were randomized to one of four groups by preparation (MPA vs TA) and dose (20 mg vs 40 mg). All groups’ pain and function improved from baseline, but there were no differences between any of the four groups by either preparation or dose.85

A systematic review showed equal efficacy between NSAIDs and corticosteroids in SASDB injections.86

Biceps tendon sheath injection

A study showed that as much as 43% of patients with anterior shoulder pain presumed to have originated from the biceps tendon had normally appearing biceps tendon.87 The others had tendinosis, tenosynovitis, or both, or tendon tear.

An RCT noted the accuracy (location of contrast in the tendon sheath confirmed by CT) of USG to be 87% compared with 27% for landmark technique.88 Another RCT showed significantly better pain relief with USG injection than ‘free-hand injection’ without US, and significantly greater improvement in the Constant-Murley score at 31–34 weeks follow-up.89 A later RCT compared the superior accuracy of US over palpation-guided injection into the bicipital groove (100% vs 68%) with less discomfort.90 Pain relief and improvement in QuickDASH scores at the 4 weeks and 6 months follow-up were significantly better with US. An additional benefit of US is that it permits visualization of the anterior circumflex artery in proximity to the tendon and potentially avoid it.

Fluoroscopy-guided injections were noted to be effective in relieving the pain from biceps tendinitis.91 However, this retrospective study only looked at six patients. US was noted to be more accurate than fluoroscopy-guided biceps tendon sheath injection. A 10-year retrospective review noted that the first-pass rate (91% for US vs 74% for fluoroscopy) and final-pass rate (98% vs 90%) were better for US, with no difference in pain relief or complications.40 An additional benefit of US is the visualization of abnormalities of the biceps tendon.

The commonly used doses are triamcinolone 40 mg in 9 mL bupivacaine90 or 40 mg TA in 1 mL lidocaine (reduced to 20 mg in patients with diabetes).89 There are no dose-response studies.

Biceps tendon rupture is usually due to degenerative changes and to trauma.92 Tendon rupture can be a consequence of CSI (see section on adverse events cartilage, ligament and tendon health).92–94 Interestingly, peritendinous CSI has been used as treatment for partial biceps tendon tear.92 Vardakas et al described seven cases of partial tear; four of the seven had ‘at least one injection of steroid’ as treatment. They did not state the effect of CSI but rather discussed the surgical technique that followed.92 Lee et al discussed 21 patients with biceps tendinitis and partial rupture who were treated with CSI (USG injection of TA 40 mg in 1 mL NS and 2 mg ropivacaine into the tendon sheath): 10 patients with biceps tendinosis had good to excellent results, while three patients with partial tear had good to excellent results.95

Scapulothoracic bursa injection

Landmark scapulothoracic bursa injections have been described. The patient is in prone position, with the affected arm in extension, internal rotation, and adduction, attempting to reach the upper spine, in what is known as the ‘chicken wing’ position.60 61 The spinal needle is inserted midway between the spine of the scapula and the inferior angle of the scapula and three to four fingerbreadths from the vertebral border of the scapula. This is not frequently done because of the risk of pneumothorax. A USG subscapularis muscle injection has been described, with the insertion site at the lateral border of the scapula.61 TA 40 mg subscapularis muscle injection provided equal relief for up to 3 months, compared with subscapularis bursa injection. Either TA 40 mg in 4 mL lidocaine or TA 40 mg plus hyaluronate resulted in significant relief of pain of up to 3 months.60 61

Comparison of corticosteroids versus other therapeutic modalities or agents in shoulder injections

A meta-analysis of single CSI versus conservative management with NSAIDs for shoulder pain (ACs, subacromial impingement syndrome, nonspecific pain, tendinitis) was performed and included eight RCTs involving 465 subjects.96 CSI showed favorable benefit over NSAIDs for improved function (Disabilities of the Arm, Shoulder, and Hand (DASH) and Oxford Shoulder Score) at 4–6 weeks (primarily seen for ACs and painful shoulder rather than shoulder impingement) but no benefit in pain relief. No differences in complication rates were noted.96

A meta-analysis including six RCTs (301 subjects) compared CSI with PRP for pain associated with rotator cuff lesions (tears, tendinosis, impingement). The analysis found short-term (3–6 weeks) benefits in pain relief and function for the CSI group, but no clinical differences at either intermediate (8–12 weeks) or long-term outcomes (over 12 weeks).97

A review and meta-analysis of three studies noted that, in patients with subacromial impingement syndrome, SASDB conferred short-term functional improvement compared with PT at 6–7 weeks, but otherwise there were no differences in pain, function, or ROM up to 12 months.98 However, there may be an additive benefit of combining PT (specifically resistance band training) to SASDB to improve ROM and reduce the need for retreatment of subacromial bursitis after SACS.99

Adverse effects of shoulder corticosteroid injections

A review of RCTs evaluating guidance-based shoulder CSI directed to the glenohumeral joint, the subacromial subdeltoid space, or tendon sheaths compared landmark-guided versus image-guided (fluoroscopy or US). There was a trend towards lower AEs (all mild) for image-guided CSI, although not significant.79

In 1979, 13 cases of tendon rupture were reported after corticosteroid injection, seven of which involved the long head of the biceps.93 Triamcinolone 40 mg in procaine was injected in the cases. The interval from injection to rupture ranged from 3 days to 5 months. Treatment was conservative; three required surgical repair.93 A case report noted the progression of a partial tear of the biceps tendon to complete tear after a palpation-guided corticosteroid injection.94 As noted previously, peritendinous CSI has been reported in patients with partial biceps tendon tear.92 95

AEs related to CSIs are discussed in the section on general AEs.

Comments

In this section, we discussed different shoulder injections: IA, SASDB, and biceps tendon sheath. SRs specific to these approaches are presented in box 4. General comments, not noted in the SRs, include the following:

Studies and reviews had conflicting results and conclusions. Overall, US improved the accuracy of acromioclavicular and glenohumeral joint, SASDB, and biceps tendon sheath injections. This did not translate into better functional outcomes in acromioclavicular joint or SASDB injections.

Peritendinous CSI into the biceps tendon has been reported to be effective in patients with biceps tendinosis and in patients with partial tear of the biceps.

Peritendinous CSI injection is controversial in view of possible tendon rupture when the injection is made into the tendon. For this reason, we did not create an SR. The clinician is advised to make an informed decision with the patient.

There is insufficient data to create a position statement regarding the preferred CSI approach for SASDB injections (anterior, lateral, posterior) to improve pain, function, or safety for painful shoulder disorders.

We suggest a minimum interval of 2–3 weeks, up to 3 months, between injections. A repeat injection is based on a shared decision between the patient and the physician, balancing the intensity of the recurring pain and the adverse events associated with CSI.

Medial and lateral epicondylitis/epicondylosis

Painful syndromes in the elbow, including lateral epicondylitis/epicondylosis (LE) and medial epicondylitis/epicondylosis (ME) when refractory to conservative management (including PT), are sometimes treated with CSI. LE, commonly known as ‘tennis elbow,’ presents with lateral elbow pain reproduced with extension of the wrist. ME, commonly known as ‘golfer’s elbow,’ presents with medial elbow pain reproduced with flexion or pronation at the wrist. ME can also be reproduced with provocative maneuvers enhancing this motion or with valgus stress testing.

Injection treatment for lateral epicondylosis

A study noted similar results in terms of pain relief and functional outcomes after USG or palpation-guided betamethasone injection of the lateral epicondyle.100 As noted previously, a study showed significantly better efficacy of combined corticosteroid and local anesthetic, compared with local anesthetic alone, in patients with lateral epicondylitis.19

Several systematic reviews have examined CSI for LE.101–106 An early review found the role of CSI for LE to be mostly inconclusive, but CSI for LE might provide benefit in short-term (2–6 weeks) relief.106 Another early systematic review of CSI for elbow and shoulder tendonitis105 found short-term (<8 weeks) benefit of CSI, without long-term benefit compared with pooled other comparators (placebo, PT, NSAIDs). Another review identified 12 studies and characterized the findings as indicative of strong support for the efficacy of CSI in the short term compared with no intervention, NSAIDs, PT, and orthoses.104 However, CSI was found to be less efficacious, in terms of reduction of pain, than no interventions at 26 and 52 weeks.104 A review of therapies for LE favored CSI for short-term improvements in pain, function, and global improvement over placebo, local anesthetic, orthoses, PT, and oral anti-inflammatories.107 However, PT and NSAIDs were more effective in the long term. Furthermore, CSI was associated with more frequent LE recurrence compared with PT alone.107 A later review identified 10 clinical trials assessing CSI for pain due to lateral epicondylosis, seven of which were published after 2000. CSI conferred analgesic benefit for up to 8 weeks after an injection for LE.102 Overall, the reviews noted short-term (<8 weeks) relief from CSI.

An RCT (not described in the identified systematic reviews noted above) compared NSAID therapy, PT, and CSI for treatment of 60 patients with LE. Patients receiving PT showed modest improvement in grip strength at 2 weeks and improved pain at 2 weeks and 4 weeks compared with the CSI and NSAID.108

A recent RCT compared stretching and splinting therapies, deep friction massage, and CSI for the treatment of LE (n=41) and found improvement (decrease in VAS score) for those patients treated with CSI at 6 and 12 weeks (from 45.4 to 31.4) as well as improvement in grip strength (from 46.7 to 60.5 pounds).109 However, similar clinical improvement was also seen in the traditional therapy and deep friction massage groups at early follow-up, with no statistical difference among the steroid, therapy, and massage groups. Neither the CSI nor the stretching and splinting group sustained improvement in VAS score at 6-month follow-up, and only the deep friction massage group experienced improved pain (6.7 to 1.3, p=0.002) and function (disability of the arm, shoulder, and hand; DASH—a 30-item questionnaire based on the patient’s ability to perform specific activities related to daily living and recreation, and weakness and stiffness of arm, shoulder, or hand score increase from 48.6 to 10.3) at 6 months.

In the studies reviewed above, TA or MPA were mostly used, with betamethasone and dexamethasone used in very few investigations. Doses of TA employed the whole range (20, 40, 80 mg), 20 and 40 mg for MP, 6 mg for betamethasone, and 4 mg for dexamethasone; 1–2 mL volumes were injected.

Corticosteroid injections versus platelet-rich plasma and autologous blood for LE

Other reviews have compared CSI for LE with PRP110 and autologous blood. A review and meta-analysis comparing the safety and efficacy of injection of autologous blood products with corticosteroids for the treatment of LE identified a total of 10 studies with 509 patients.101 CSI was more effective in the short term, but autologous blood products provide more pain relief and improved function in the intermediate and long term. The study described high recurrence rates of LE following CSI, 72% at 6 weeks and 37% at 6 months.

Another meta-analysis compared CSI with PRP and autologous blood in terms of improved function and pain.111 Of the 10 studies analyzed, comparisons between PRP, autologous blood, and CSI focused on three studies with results from within 2 months. These studies favored PRP and autologous blood in terms of improved function and pain pressure threshold. However, CSI had a more favorable AE profile compared with autologous blood.111

Finally, a meta-analysis showed limited favorability for CSI over PRP in the short term (4–8 weeks), but no difference in the long term (24 weeks).110

AEs from CSI in lateral epicondylosis

Common AEs include postinjection flare, minor rash, transient pain (around 11%), skin atrophy, and depigmentation (4%).105 107 In one study, the rate of pain following CSI was substantially higher compared with injection of local anesthetic (50% vs 11%).112 No serious AEs such as tendon rupture or infection were identified in the reviews. There is a statistically higher risk of local pain and skin reaction after injection of autologous blood compared with CSI but not between PRP and CSI or PRP and autologous blood.111

Injection for medial epicondylosis

There is a paucity of studies investigating CSI for ME. Injection of 40 mg MPA in 1 mL lidocaine provided better short-term benefit at 6 weeks over lidocaine and saline injection.113 However, there was no difference in effect at 3 months and 1 year. The authors believed that the improvement reflected the natural history of the condition.

Intra-articular elbow joint injection

Pain associated with the elbow joint may be due to OA, RA, or crystalline arthropathies.114 115 Few publications have focused on IACS for the elbow, and there were no pharmacokinetic studies after elbow IACS injections. When the elbow was studied, it was one of several joints included in the study.

Injection for olecranon bursitis

A 2016 RCT evaluated the resolution of non-septic olecranon bursitis comparing 90 patients randomly assigned to either NSAIDs (and compression bandaging), aspiration, or aspiration with CSI (n=90; 40 mg TA in 1 mL lidocaine) for the treatment of non-septic olecranon bursitis.116 The proportions of patients experiencing resolution (by VAS score) by week 4 were similar among the three groups. CSI with aspiration was associated with the earliest mean resolution at 2.3 weeks compared with aspiration alone (3.2 weeks) or NSAIDs with compression bandaging (3.2 weeks). There were no AEs or complications reported.

In summary, CSI confers short-term (up to 8 weeks) pain relief for LE. Further research is required on the utilization of CSI for ME and olecranon bursitis. For this reason, no SR is provided for medial epicondylosis. For SRs on IACS in shoulder and elbow, see box 4.

Hip pain

Hip pain is most commonly caused by OA or other inflammatory arthritis (such as autoimmune or crystalline disease) of the femoral-acetabular joint, and by greater trochanteric pain syndrome (GTPS). Other reasons for hip pain include osteonecrosis, femoral acetabular impingement, or labral tear.117 118 CSIs are used for patients who fail to respond to pharmacological and non-pharmacological managements, or for patients who are looking for short-term pain relief where hip surgery is either not an option or delayed.10 18 118–120

As noted earlier, the recommendations from different organizations regarding IACS into the hip are listed in table 3.10–12 16–18 121

General comments on image-guided hip injections

IACS injections can be performed using landmark technique, fluoroscopy, US, or CT.69 122 123 Fluoroscopically guided hip injections were noted to be more accurate than non-image-guided hip injections.124 For diagnostic purposes only, one study showed comparable accuracy between USG and fluoroscopy-guided injections in obtaining arthrography of the hip joint,125 while another study noted similar accuracy, less pain, and better patient preference in USG injections.126 A review noted the absence of comparative data to show increased accuracy with US or X-ray guidance in IA hip injections.17

Corticosteroid versus non-corticosteroid anti-inflammatory intra-articular injections

A retrospective comparative study showed no difference in efficacy between IA 40 mg triamcinolone and 30 mg ketorolac in patients with hip OA; the verbal numeric pain scores did not show differences at 1, 3, and 6 months.127 A double-blind RCT study examined comparative effectiveness of USG IACS injection with IA ketorolac injection in patients with symptomatic hip OA.128 IA injections with either ketorolac or triamcinolone produced significant improvements in patient-reported outcome measures, with the largest improvements at 1 week, which decreased over time. There were no significant differences between ketorolac and triamcinolone. There were no significant side effects from either intervention. Ketorolac could therefore be considered in patients at risk for steroid AEs, as a low-cost option.69 128

An RCT examined the comparative efficacy of IA hip injections of hyaluronic acid, corticosteroid, and normal saline in patients with hip OA.129 Patients treated with 40 mg triamcinolone experienced greater improvement 28 days after IACS injection than did patients assigned to the hyaluronic acid group. The outcome domains were pain on walking and at rest, WOMAC, and Lequesne index. There was no difference in the patients’ global assessment of pain. Hyaluronic acid had a considerable effect on patients without effusion but had no effect in the patients with effusion. On the contrary, corticosteroids influenced both patients with and without effusion. The peak effect of the CSI was observed 2 weeks postinjection. The improvement from normal saline injection was insignificant.129 Another prospective RCT produced a similar result.130 Patients with hip OA were randomized to one of four groups, including non-interventional care (no injection) group and three groups receiving injections: normal saline, hyaluronic acid, and MP. The CSIs were found to be highly efficacious, specifically pain, WOMAC pain, and function improved significantly for the steroid group alone.130 The corticosteroid response was maintained for 8 weeks.

Three systematic reviews compared IACS with placebo (saline), PRP, and hyaluronic acid. The studies were heterogeneous in the degree of OA, all trials with different sample sizes, medications used, and timing of follow-up. The most used dose was 40 mg triamcinolone or MP. All reviews showed improvement in pain and function with IACS that lasted 4 or 6 months.131–133 IACS showed better results than hyaluronic acid.131–133 In a network meta-analysis (with the same above limitations), despite no mean statistical differences across treatments (including saline), IACS was rated as the most favorable treatment by surface under the cumulative ranking curve (a score that represents numeric ranking of treatments, with a greater value indicating greater efficacy) analysis at 2–4 months (both pain and function), whereas HA and PRP had favored rating at 6 months.133

Two recent systematic reviews compared the clinical outcomes, in terms of pain and function, between NSAID injection and IACS in hip OA. One review noted no difference86; both groups showed significant improvement for 3–6 months. The other concluded that IACS injections were more effective.134

Volume of injectate and dose of corticosteroid

The reported volumes of IA hip injection vary from 3 mL to 12 mL. In one randomized study, patients were given either 40 mg triamcinolone and 2 mL bupivacaine or 6 mL of sterile water injection. There was no significant statistical or clinical difference in functional scores between the two groups at 3 months. Since there is no detriment to using a larger volume of injectate, the investigators recommended that practitioners use total volumes between 3 and 9 mL.135

As noted in the above studies, the most commonly used dose for hip IACS is 40 mg triamcinolone or MP.

For statements and recommendations on IACS in hip and knee injections, see box 5.

Peri-articular hip injections: greater trochanteric bursitis, gluteus tendinopathy, snapping hip syndrome

GTPS is characterized by pain around the greater trochanter and may radiate distally over the lateral aspect of the thigh. It is more common in women. GTPS can be caused solely or by a combination of trochanteric bursitis, gluteus medius or minimus tendinopathy, or snapping hip (palpable or audible snapping with active hip motion).136 The current thinking is that GTPS is mostly caused by gluteal tendinopathy.

Use of imaging in peri-articular hip injections

Earlier reports suggested that peri-articular hip injections (figure 2) can be performed using landmarks, fluoroscopy, or US.35 146–149 A cadaveric study of 24 hip specimens (body mass index unknown) compared the accuracy between landmark-guided and USG greater trochanteric bursa injections.150 The accuracies (intrabursal injection) were 67% for landmark vs 92% for USG, with no statistically significant difference (p=0.25), although the study may be underpowered to detect a statistical difference. Using landmark guidance, a clinical study showed attainment of a bursagram in 45% of the patients on the first attempt, 23% on the second attempt, and 23% on the third attempt.147 In a subsequent study, the same investigators noted similar positive bursagram and similar functional outcomes (Oswestry scores, 36-Item Short Form Survey, patient satisfaction) between fluoroscopy and landmark-guided trochanteric bursa corticosteroid injection (60 mg MPA plus 2.5 mL local anesthetic).148 In patients with obesity, trochanteric bursa injections under fluoroscopy significantly reduced immediate and 1-week postinjection pain scores.151

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Figure 2

Injection sites for hip pain. A—iliopsoas bursa; B—gluteus medius/minimus tendon sheath; C—greater trochanter bursa; D—hip joint. Note that the injection is around the gluteus medius/minimus tendon or tendon sheath. Image courtesy of Sebastian Encalada, MD, Mayo Clinic, Jacksonville, Florida.

There has been no study that compared US and landmark injections; most studies used US guidance, and two involved fluoroscopy.148 151 While studies showed no statistically significant benefit with imaging (fluoroscopy or US), the use of fluoroscopy or US is recommended in patients with obesity where palpation of the greater trochanter can be difficult or when landmark-based injections have failed.

US guidance has been recommended for tendon sheath injections and iliopsoas bursa injections.152 There has been no study that compared landmark with US in gluteus medius/minimus tendon injections. Visualization of the tendon with US is an obvious advantage to prevent intratendon injection and possible rupture.

There has been no study comparing iliopsoas injection with image-guided (US or fluoroscopy) versus landmark-guided techniques. Fluoroscopy-guided iliopsoas bursa CSI (TA 40 mg in 5 mL lidocaine) has been described with the center of the acetabular roof as the target area and confirmed by injection of contrast.153 The study of 39 patients showed 49% had ‘clinically relevant improvement’ at 1-month follow-up. A cadaver study noted 90% accuracy with USG injection, with the injectate covering 50%–100% of the iliopsoas tendon.154

Treatment of GTPS, efficacy of injections

Treatments of GTPS include PT, analgesics, NSAIDs, injections; surgery is performed in recalcitrant cases.

Comments, statements, and recommendations for pericapsular hip injections

In the previously cited studies, the site of pericapsular hip injections was not clear. In some studies, the injection was made into the site of maximal tenderness or swelling, peritrochanteric bursa if visualized or landmark-guided insertion of the gluteus medius tendon into the greater trochanter, per discretion of the provider (surgeon or physician assistant), or the site of injection was not noted. In one study, the diagnosis was gluteus tendinopathy, but the injection was into the trochanteric bursa. This is partly explained by the varied etiologies of pericapsular hip pain and the inclusion of various etiologies in studies. Owing to this heterogeneity, we are not providing statements or recommendations related to pericapsular hip injections. However, in view of the better efficacy of CSI over home training, usual care, or shock wave therapy shown in some studies, it is reasonable to initiate therapy with CSI in pericapsular hip pain.

Iliotibial band friction syndrome

Iliotibial band friction syndrome results from repetitive friction between the iliotibial band and the lateral femoral condyle. It is usually seen in runners and cyclists and has been reported after knee cementoplasty. The syndrome is characterized by lateral knee pain, aggravated by knee flexion and relieved by full knee extension. Treatments include rest, reduced running, NSAIDs; surgery is performed in refractory cases. An RCT compared CSI with MPA 40 mg and local anesthetic with local anesthetic injection into the point of maximal tenderness in the lateral femoral condyle.167 The decrease in pain during running was significantly better with the CSI at the 7 and 14 days follow-up. There were no complications, although only 18 patients were studied.167 There is a case report of iliotibial band rupture 2 months after several CSIs (three CSIs—40 mg TA in 8 mL local anesthetic) every 2 months) in a patient with iliotibial band friction syndrome.168

Landmark versus image-guided knee injections

A prospective study compared the accuracy of different approaches with the landmark-based needle IACS into the knee. There was a 75% accuracy rate with the anteromedial approach and a 93% accuracy rate with the lateral midpatellar approach.169

A prospective randomized study examined differences in patient satisfaction, functionality, and the quality of life in adult patients receiving USG versus landmark-guided knee aspiration followed by IA CSI.170 It was noted that USG injections resulted in greater improvement in pain indexes and better patient satisfaction and quality of life scales after 4–6 weeks compared with landmark techniques.170 USG knee joint aspiration and injection resulted in significantly less procedural pain, greater synovial fluid yield, and more complete joint decompression. The same positive outcome measures, plus improved clinical outcomes were noted in another knee study.171 A recent review of 12 published clinical studies, seven of which directly compared US with landmark-guided knee injections, all noted better accuracy with US in each of the seven studies.172

Comparative effects of different corticosteroids and dose-response studies

Studies comparing different corticosteroids, including extended-release preparation, were mostly done in knee injections (see section ‘extended-release corticosteroid preparations’). As noted earlier, research to date has not demonstrated long-term superiority of one corticosteroid preparation for IA knee injections.24

Dose-response studies and long-term efficacy of knee IACS

In a 12-week double-blind RCT, 80 mg of IA TA was compared with 40 mg of TA.173 Of the two doses, 80 mg was not found to be superior to 40 mg for IA in terms of pain relief or functional improvement.

Neither IA injections of corticosteroid nor hyaluronic acid provided sustained symptom relief over 2 years.174 A clinical evidence synopsis concluded, with low-quality evidence, that IACS for knee OA may be associated with moderate improvement in pain and a small improvement in physical function up to 6 weeks after injection.175 A systematic review and meta-analysis confirmed the short-term (up to 6 weeks) superiority of IACS in the knee, while long-term follow-up (24 weeks or longer) showed a trend towards superiority of controls (IA hyaluronic acid, IA NSAID, PT).176 A systematic review of guidelines also noted the short-lived improvement (<4 weeks) with IACS into the knee joint.177 A recent systematic review noted no difference in outcomes between IACS and NSAID injection into the knee joint; both showed improvement at 1 and 3 months.86

We previously discussed the pharmacokinetic and pharmacodynamic studies after knee IACS (see section ‘pharmacokinetics and timing of responses’). In summary, pain relief is noted at 1–2 weeks after injection. Such relief extended to 12 weeks.33 The timing of these responses coincided with the T_max and T_1/2 concentrations of the corticosteroid.27 28 33 For this reason, we suggest follow-up at 2 weeks to 3 months after injection.

Postinjection protocol to optimize efficacy and safety

After a CSI into a joint, it is common for physicians to limit activity to minimize possible chondrotoxic effects, systemic absorption, and potentially improve outcome. In a survey, 29% of rheumatologists did not restrict weight bearing after a corticosteroid knee injection, while 8% of rheumatologists restricted weight bearing for up to 1 week.20 In another survey, 42% of respondents recommended avoidance of weight-bearing after knee joint steroid injection. There was an increased likelihood that rheumatologists (71%) would recommend limited weight-bearing for 1 or 2 days as compared with general practitioners (57%) and orthopedic surgeons (3%).178 A Cochrane review found low-quality evidence to support splinting/resting a knee in this population after injection, but not the wrist.179 In one trial, there was significant improvement in pain, stiffness, knee circumference, and walking time in the rested group (no point estimates were provided).180 In pediatric patients, a retrospective observational study of two pediatric hospitals showed no clear benefit of rest/splinting postinjection after knee IACS.181 In fact, patients who had postinjection splinting had a trend toward more arthritis recurrence (38% vs 26%, p=0.14).

Adverse events related to knee joint corticosteroid injections

The local AEs for the knee include joint destruction, avascular necrosis, and Nicolau syndrome (ie, variable degrees of skin and underlying tissue necrosis).182–184 Discussion on cartilage health and systemic adverse events are included in the section of general adverse events.185

In summary, USG IACS knee injections are more efficacious (less procedural pain, greater aspirate volume, and better short-term outcomes) than landmark-assisted injections. There is no long-term superiority between the different corticosteroids. Triamcinolone at a dose of 40 mg is as effective as 80 mg. Relief from IACS is short-term (up to 6 weeks). For SRs on IACS in hip and knee joints, see box 5. In view of the pharmacokinetic and pharmacodynamic studies on knee IACS, we suggest a minimum 2-week interval between injections.

Wrist and hand corticosteroid injections

CSI of the joints of the wrist, hand, and small joints have been reported for treatment of both inflammatory and non-inflammatory arthritis.186–197 In a prospective open-label study, 30 subjects with RA had USG CSIs into wrist and/or hand joints, using 40 mg TA for the wrist joints and 20 mg TA for metacarpophalangeal (MCP) and proximal interphalangeal joints. There was a statistically significant improvement in visual analog pain scores, swelling, tenderness, synovial hyperplasia, and power Doppler signal scores at 4–12 weeks postprocedure as compared with baseline for all joints.187

While select individual RCTs have shown efficacy of corticosteroids over placebo in IA injections in osteoarthritic interphalangeal joints for treatment of pain, this has not held true when data are analyzed in aggregate.196 A systematic review of 13 RCTs showed no overall benefit for CSI over placebo.195 One trial showed no improvement in pain after CSI in the carpometacarpal joint for the treatment of OA.198 Another trial demonstrated significantly less pain during movement, but not at rest, in patients with interphalangeal OA; the authors concluded that this isolated finding requires confirmation.199 Another systematic review demonstrated with low-to-moderate quality data that IA saline is superior to CSI in trapeziometacarpal (so-called ‘thumb base’) OA when confirmed with radiography using pain and function as end points.197 The ACR provided a conditional recommendation for IACS in hand OA.10

Beneficial effect of US-guided injection

The use of US guidance for wrist and hand CSIs appears to be beneficial.171 186 187 200 USG IACS into the distal radioulnar joint were significantly more accurate than landmark-guided IACS (100% vs 75.8%, respectively).201 Of note, the study demonstrated no significant difference in clinical outcomes between the USG CSI and the landmark injection technique groups.201

A meta-analysis of four studies comparing USG wrist and hand CSIs with landmark-guided injections showed that the USG injection technique was more likely to result in decreased pain and increased function at a 6-week follow-up interval.200 In one study, USG injections for patients with RA demonstrated improvement in pain and function as compared with landmark-guided injections and an 8% reduction in cost. It should be noted that in this study, only 3% of the joints injected were ‘small joints.’188

Postinjection management after wrist injections: rest versus activity

Unlike knee IACS injection, there appears to be no benefit with rest after wrist injection. A trial noted an increase in relapse rate, with no difference in pain relief, wrist function, grip strength, or ROM in the patients who had 48 hours of rest using elastic wrist orthoses, compared with the non-rested group.202

Trigger finger

Stenosing tenosynovitis, known as ‘trigger finger,’ is snapping or locking of a finger or thumb, usually at the MCP joint. It is caused by the disproportion of the volume of the tendon sheath and its contents, inhibiting the straightforward gliding of the tendon through the digital pulley (structure that holds the tendon against the finger bone). A dose-response study showed significantly better results with 20 mg TA compared with 5 and 10 mg at 3 and 6 months of follow-up. However, there were no differences at 9 and 12 months.203 A 2018 systematic review found moderate evidence for the benefit of CSI in the short term (0–3 months) for the treatment of trigger finger.204

A prospective case-control study evaluated USG and palpation-guided trigger finger injections with corticosteroids and found no differences at 6 weeks or 6 months in terms of clinical efficacy. There was a significant increase in procedural time and effort with US.205

De Quervain’s tenosynovitis

De Quervain’s disease is non-inflammatory thickening of the ligament overlying the tendons in the first dorsal compartment of the wrist, impeding the gliding of the adductor pollicis longus and extensor pollicis brevis tendons. This hinders the function of the thumb and produces pain in the thumb side of the wrist. A systematic review evaluating CSI versus placebo and acupuncture for De Quervain’s tenosynovitis showed moderate benefit for CSI in the short term (0–3 months). The review also demonstrated that there is moderate evidence that a thumb splint added to a CSI leads to effective treatment in the short term and intermediate term (0–3 and 4–6 months, respectively).204

Plantar fasciitis

The terms ‘plantar fasciitis,’ ‘heel pain,’ and ‘plantar heel pain’ are often used interchangeably in the medical literature.206 207 Etiologies include biochemical (extreme pronation of the talar joint), anatomic (flat foot), and chronic disease (diabetes, obesity). Pathophysiology can either be inflammatory, secondary to immune system activation and vasodilatation, or non-inflammatory from fibroblastic hypertrophy.208 Deposition of corticosteroids in or near the origin of the plantar fascia has been used as a treatment for plantar heel pain for decades.209 A 2017 Cochrane review evaluated 42 studies (36 were RCTs) to assess the efficacy of CSIs in the treatment of plantar fasciitis. The data supported the use of CSIs over placebo or no treatment but only up to 1 month.206 A 2019 systematic review, comprisingd 47 trials, concluded that CSIs for plantar heel pain were more effective than autologous blood or foot orthoses in reducing pain and more efficacious than PT in improving function, but only in the short term (up to 6 weeks). Notably, CSI was not more effective than placebo in terms of pain relief or in improving function.207 The authors noted that in the long term (13–52 weeks), PRP injections and dry needling were superior to CSIs.207 The majority of trials were small (mean size 28 subjects) and had significant risk of bias (most frequently due to lack of blinding) resulting in low or very low quality of evidence. Another 2019 systematic review and meta-analysis based on 31 RCTs demonstrated that there was no difference in outcomes for plantar heel pain between CSIs, oral NSAIDs, therapeutic exercise, orthoses, or extracorporeal shockwave therapy.210

An important distinction is the treatment of plantar heel pain associated with rheumatological inflammatory arthritis, especially spondyloarthritis. Enthesitis, or inflammation, at the site of attachment of tendons and ligaments to bones, is characteristic of spondyloarthritis. A systematic review of the treatment of this subset of plantar heel pain associated with rheumatological inflammatory diseases included five studies. All studies demonstrated efficacy and safety of USG CSI.211

The corticosteroids used in the above studies were MP, triamcinolone, betamethasone, and dexamethasone. There were no dose-response studies; the doses ranged from 20 to 80 mg for MP and TA, 6 mg for betamethasone, and 4 to 8 mg for dexamethasone. In the studies that noted the repeat injections, the interval between injections was 2, 3, and 6 weeks, and 3 months.206

Known complications of plantar fascia injections with corticosteroids include fascial rupture and fat pad atrophy.206 212 213 A longitudinal cohort study followed 174 patients for 5–15 years, where the patients received USG steroid injections of the plantar fascia for 5–15 years. At follow-up, the mean fat pad thickness in the patients who received USG CSI was 9.0 mm (95% CI 7.0 to 10.9 mm) compared with 9.4 mm (95% CI 7.2 to 11.6 mm) in the patients without an injection (p=0.66).209 The decrease in thickness could be due to age/aging or the corticosteroid, which reduces edema by decreasing inflammation. In this study, no patient experienced a fascial rupture.

For SRs on small joint injections, see box 6.

Similar to corticosteroid joint injections, clinicians should limit the use of IACS injections into the small joints of the wrist, hand, and foot. Repeat injections should be based on the patient’s response.

Bleeding

In a retrospective study of 514 patients on therapeutic anticoagulation with warfarin who underwent a total of 640 joint injections and/or arthrocentesis, a single incident of clinically significant bleeding in an anticoagulated patient (international normalization ratio (INR) 2.3) was found (rate of 0.2%).227 A total of 456 procedures were performed when INR was >2.0, and 184 procedures were performed with INR <2.0. Another single-center retrospective study of adult patients on novel oral anticoagulants found no incidents of bleeding among 1050 consecutive procedures, with the authors concluding that holding oral anticoagulation prior to joint injections is not warranted.228

The ASRA PM recommends that patients on anticoagulant and antiplatelet medications without additional complicating coagulopathic conditions (advanced liver disease or cirrhosis, advanced renal disease, old age, history of bleeding/hemophilia, or multiple anticoagulant medications) may continue their anticoagulant or antiplatelet treatments without interruption for low bleeding risk procedures (such as peripheral joint injection) as the risk for stopping these medications likely outweighs the low risk of bleeding for those on therapeutic dose.229 Indeed, even patients with knee pain due to hemophilic arthropathy have been shown to derive benefit from IACS, and knee injections have been shown to be performed safely in this population with use of US and power Doppler.230

Cartilage, ligament, and tendon health

One of the concerns with IACS for the knee is the potential AE of IACS on cartilage health. Potential detrimental effects include catabolic effects on cartilage proteins including aggrecan, type II collagen, and proteoglycans, chondrocyte availability, and gross cartilage morphology.231–234 Animal studies investigated the effects of corticosteroids on cartilage with inconsistent and conflicting results.231 232 235–237 Some of these studies demonstrated cartilage disruption, while others showed cartilage preservation during acute inflammatory events. For commonly employed corticosteroid preparations, such as MP, betamethasone, and triamcinolone, basic science and animal studies have demonstrated a dose-dependent detrimental effect on cartilage.

A 2-year randomized placebo-controlled, double-blind trial of IA TA versus saline for symptomatic knee arthritis in 140 patients using annual knee MRIs, IACS resulted in greater cartilage volume loss than saline injection.238 In this study, the intervention (saline or 40 mg triamcinolone without IA local anesthetic administration) was administered every 12 weeks for 2 years. Patients received MRIs at 0 (baseline), 12, and 24 months, and mean cartilage thickness was computed. The cartilage loss was more significant with the corticosteroid, and a corresponding response with pain improvements did not occur, raising concern about the value of frequent repeat IACS for the knee.

As noted previously, cases of tendon rupture were reported after injection into the biceps tendon or into the iliotibial band.93 94 168 The long-term risks of repeated injections of the tendon sheath have not been reported, but in vitro studies indicated damage to chondrocyte viability after exposure to MP.239 Single doses of USG injections of the biceps tendon do not appear to cause changes in tendon elasticity.240 Practitioners may choose to exercise caution in performing repeated CSIs of the biceps tendon or iliotibial band.

Accelerated joint space narrowing and osteonecrosis

An IACS knee RCT study (40 mg IA TA injections administered every 3 months vs saline placebo for up to 2 years) used X-rays (rather than MRI) to examine radiological progression of joint space narrowing.241 The study was powered (34 patients per group) to detect a difference of 0.125 mm progression of joint space narrowing between the two treatment groups at 2 years. No difference between the groups was detected at either 1-year or 2-year follow-up.

A study used radiographic findings to assess progression of joint space narrowing or joint destruction (semi-quantitative 0–4 scale) in 30 individuals with OA and 35 with RA who underwent a minimum of 15 knee CSIs over a 4-year period and a maximum of 167 injections over a 12-year period.242 Fifty percent (36) knees showed no or minimal progression between radiographs (duration not described). Ten knees showed marked deterioration (marked narrowing with some collapse of a condyle and/or lateral subluxation). Two knees (same patient) revealed gross deterioration (Charcot’s type joint), over 7 years after 82 and 85 IACS provided for each knee. However, there was no correlation between the number of injections and the rating of joint deterioration. Again, follow-up radiographs were done for clinical indications (not by protocol) with variable follow-up (not described). The total number of injections rather than frequency per year were described; laterality was not addressed. The authors concluded that repeated IACS do not lead to rapid joint destruction.

An updated Cochrane review of IACS for knee OA found that corticosteroids had no effect on joint space narrowing compared with control interventions (SD −0.02; 95% CI −0.49 to 0.46).243

Two retrospective studies showed progression of OA with IACS (based on Kellgren-Lawrence radiographic grading of OA) compared with non-injected controls. One is a small retrospective study with hip OA, and244 the other is a bigger multi-institutional study of 684 patients with knee OA.245 The retrospective study of 70 patients with hip OA compared with a matched control group showed that 44% (31 of 70) of patients who were given injections of corticosteroids with local anesthetics had radiographic progression of their OA, and 17% (12 of 70) experienced collapse of the articular surface.244 The two radiologists, blinded to receipt of hip injection, found osteonecrosis in eight to nine images prior to injection and new osteonecrosis in 16–19 images postinjection. There was a very high prevalence of X-ray defined osteonecrosis in both the IACS group (37%) and comparator group (24%).244 The larger multicenter longitudinal observational study followed 684 propensity-score matched participants. Using either an increase in the Kellgren-Lawrence grade by >1 or a decrease in joint space by >0.7 mm for knee rapid OA progression, the authors noted an association between IACS and knee radiographic OA progression.

Finally, there is also a case report of collapse of the superior femoral head articular surface after IACS administration in a patient with osteonecrosis but with preserved femoral head contours.122 This progression has to be kept in mind since patients with painful non-collapsed osteonecrosis of the femoral head are frequently referred for IACS. The case also demonstrates value in radiographic imaging before IACS hip injections.

The risk factors for osteonecrosis include a history of BMD compromise; chronic corticosteroid exposure; and underlying disorders, such as renal insufficiency, organ transplantation, graft versus host disease, inflammatory bowel disease, HIV, and acute lymphoblastic leukemia.122 246 Bisphosphonate therapy may mitigate this risk.247

Accelerated OA progression

Rapid progressive OA (RPOA), also called rapid destructive hip disease or rapid destructive OA, is a rare condition with rapid loss of joint space on X-rays that is beyond the anticipated rate; defined as a joint space loss of >2 mm within a 12-month period.122

A report of 307 patients undergoing hip IACS noted 23 patients (7%) developed RPOA, and of the 152 patients undergoing knee IACS, 6 (4%) were observed to experience RPOA.122 This study was limited by retrospective review of the clinical care. Radiographic follow-up was incomplete, obtained only when clinically indicated, and this would result in conservative estimates. Selection bias (referral to the radiology department for image-guided injections) may have been selected for patients with more progressive OA (independent of IACS).

A recent two-part study documented an association between hip CSI and RPOA.248 In the case-control portion, the authors showed an association between CSI and RPOA, with the risk increased with higher dosage and number of injections. The risk was low with a single 40 mg triamcinolone injection and higher with higher doses (80 mg or higher) and multiple (two or more) injections. The minimum effective dose is 40 mg TA (see box 7). In the retrospective portion, the investigators noted a rate of 5.4% (37 of 688 cases) after injection. Diagnosis occurred at an average of 5 months after injection and was characterized by rapid narrowing of the joint space, osteolysis, and collapse of the femoral head.

Blood glucose

An IA corticosteroid is known to elevate blood glucose in patients with and without diabetes mellitus, although not necessarily with adverse clinical consequences in patients without diabetes. Shoulder IACS (triamcinolone 40 mg) for the treatment of ACs elevated fasting blood glucose (FBG) by 17 mg/dL in both patients with and without diabetes, resulting in higher levels at day 1 (attributable to higher baseline FBG); FBG was observed to remain above baseline up to 2 weeks following injections for both groups.249 Among 60 patients with diabetes mellitus who received IACS, fasting and postprandial blood glucose were observed to be elevated up to 3 days after injection among the entire cohort.250 However, when analyzed according to site, upper extremity injections were not found to be associated with increased fasting or postprandial blood glucose, knee injections were associated with significantly elevated fasting and postprandial blood glucose, and paradoxically, injections at multiple sites were not associated with elevated fasting or postprandial blood glucose on days 1 through 7. In multivariate analyses, high baseline glycosylated hemoglobin (HbA1c) was significantly associated with elevated blood glucose following IACS, while factors including body mass index, insulin use, and corticosteroid dose were not associated with elevated blood glucose. In this study, one patient had FBG as high as 493 mg/dL, but no patient experienced diabetic ketoacidosis.250 A study of 23 patients with diabetes undergoing IACS shoulder injection reported similar findings, namely no significant elevation of blood glucose above baseline following injection.251 One RCT of patients with diabetes on oral agents undergoing IA knee CSI compared extended-release with standard formulations of triamcinolone (32 mg) vs standard triamcinolone preparations (40 mg).31 The mean increase in blood glucose from pre-injection (days −3 to −1) to postinjection (days 1–3) was 37 mg/dL and significantly >8.2 mg/dL in the extended-release group (p=0.04); blood glucose after standard 40 mg triamcinolone was noted to peak 6 hours after the injection, with mean blood glucose of 252 mg/dL.31 A systematic review of patients with diabetes mellitus undergoing IACS identified seven studies (n=72) showing a clinically significant rise in blood glucose up to 1 week after injection, with many patients experiencing this effect within 48–72 hours after injection but not necessarily immediately following the procedure.252 In a study evaluating the effects of TH versus TA on blood glucose following IACS in patients with diabetes and symptomatic knee OA (n=12 in each cohort and n=6 in a hyaluronic acid cohort), patients experienced median elevated blood glucose >200 mg/dL following IASC, (median peak 239.5 at 32.5 hours in the TH group, 288 at 24.5 hours in the TA group) returning to normal within approximately 4 days.253 All study subjects had HbA1c <7.0. A separate small study following six patients with controlled diabetes after IACS with betamethasone to the knee joint showed a mean peak blood glucose of 322.5±67.75 mg/dL, with most patients returning to baseline within 48 hours following the injection.254

Bone mineral density

Chronic and/or high-dose corticosteroid exposure is known to affect BMD, particularly in patients with conditions requiring long-term oral medication. Excessive use of epidural CSIs has been associated with compromised BMD.255–258 Kerezoudis et al noted significant reductions in BMD were associated with a cumulative dose of 200 mg over a 1-year period and 400 mg over 3 years, and at least 3 g for healthy men. Reductions in BMD were not seen in doses of <200 mg of MP equivalents for postmenopausal women.255 Their conclusions were questioned in view of the small and underpowered studies that they reviewed.256 In a subsequent narrative review of additional studies, Stout et al recommended consideration of a maximum cumulative whole-body triamcinolone/MP dose of 200 mg/year and 400 mg per 3 years in postmenopausal women and potentially men over 50 years of age.258 They cautioned that these relative limits should be weighed against functional benefits. Additionally, another study of 352 postmenopausal women concluded that there was no association between epidural CSIs and decreased BMD or fracture risk.257 These studies are discussed in more detail in our upcoming neuraxial steroid PG.

Regarding IACS, a retrospective study in patients with RA (n=208 patients, receiving one (101 patients), two to three (51 patients) or four (56 patients)) did not find any statistically significant relationship between the number of IACS and BMD over the course of 1 year.259

A recent cohort study by Sytsma et al was published after we developed the SRs.260 This study is notable for the large number of injections and the variety of CSIs. The investigators evaluated the association between the risk of fracture and 33 864 CSIs into joints (large, medium, small), spine (facet, epidural, sacroiliac), nerve blocks, trigger points, and tendon or ligament. They did not see an association between higher fracture risk based on cumulative corticosteroid dose, with a mean cumulative dose of 141.8 mg TA equivalents (range: 2.7–2140.3 mg). Sytsma et al also noted the lack of associated higher fracture risk in the non-high-risk or osteoporosis subgroups.260 This supports the findings of the study by Kerezoudis et al, in which BMD was not decreased at doses of <200 mg of MPA/TA equivalents per year for postmenopausal women.

The recommendations of Kerezoudis et al and Stout et al were made after a careful review of the literature. Balancing the recommendations of Kerezoudis et al and Stout et al with the results of the recent study by Sytsma et al, we suggest that the clinician consider a maximum cumulative whole-body triamcinolone dose equivalent of 200 mg/year and 400 mg per 3 years in postmenopausal women. Note that the average and maximum TA equivalent cumulative dose was higher in the study by Kerezoudis et al (average of 80–81 309 mg in the eight studies) compared with the Sytsma et al study (2140.3 mg). We arrived at this suggestion to err on the side of safety, as we wait for additional studies. These limits are achievable without compromising efficacy. Routine series of injections should not be performed; subsequent injections should be repeated after observation of the patient’s response and after recurrence of the pain. The minimum effective doses of CSIs in the joints and in the spine should be administered; CS should not be added in sympathetic nerve blocks, TPIs, and most peripheral nerve blocks. We echo the recommendation by Stout et al that providers should discuss the potential of BMD loss after glucocorticoid injections with patients, especially when receiving multiple injections.

Adrenal suppression

Adrenal suppression has been documented after single IA doses of corticosteroids.261–263 Clinically meaningful adrenal insufficiency occurs when a sufficient stress requires an adrenal surge in the setting of adrenal suppression; it is an uncommon but important clinical condition that may occur more commonly or be expected in the hospital setting.

An RCT compared patients who received a single knee IACS (MPA 80 mg) with a group that received 6 mL IA sodium hyaluronate. This was followed by a low-dose adrenocorticotropic hormone (ACTH) stimulation test. The authors noted that 25% of subjects in the steroid group experienced secondary adrenal insufficiency (<7 μg/dL increase in serum cortisol level and absolute levels of <18 μg/dL 30 min after the ACTH stimulation test), observed 2–4 weeks following injection versus none in the control group.264 A systematic review and meta-analysis noted that the percentages of adrenal insufficiency ranged from 4% with intranasal administration to 52% from IA injection.265

Septic arthritis

The incidence of septic arthritis following IACS outside of the context of joint replacement surgery is rare, but patient morbidity can be devastating.

Risk factors for septic arthritis include immunosuppression, intravenous drug use, alcoholism, previous steroid injections, and cutaneous ulcers. Patients commonly present with local warmth and/or swelling, fever, and night pain, and the most involved joints include the knee and hip.

A retrospective review of 10 patients diagnosed with acute septic arthritis following knee injection found that three out of 10 patients had undergone recent injection with ‘cortisone’ (five with hyaluronic acid, two unknown).266 All patients presented with joint pain and swelling; three had decreased ROM, two had fever, and one had erythema. The mean incubation period was 11.9 days. Inflammatory markers were elevated (mean erythrocyte sedimentation rate, 52.6 mm/hour; mean C reactive protein, 10.3 mg/dL). Only half of the 10 patients had an organism identified in culture (three Streptococcus mitis, two oral flora). Comorbidities included hypertension (four patients), diabetes mellitus (two patients), and chronic kidney disease (one patient). Patients had received a variable number of injections prior to admission (0–1 in four patients, 2–3 in four patients, 4–5 in two patients). All 10 patients underwent arthrocentesis with cell culture and were treated surgically (three patients required more than one incision and drainage). Of the patients, eight were treated with antibiotics for 21 days (seven with parenteral antibiotics), and six were dismissed to a rehabilitation facility. With a broader assessment of risk factors associated with these infections, the authors concluded that the facility performing the injections had poor adherence to standard infection control protocols.

Sterile inflammatory arthritis may occur after IA injection and can be confused with septic arthritis. A systematic review identified 19 patients among 18 studies (n=286) with postinjection swelling without clinical evidence for infection consistent with synovitis.267–269 Postinjection inflammation may be due to exacerbation of calcium pyrophosphate dihydrate crystals, which has been best described after sodium hyaluronate injection.270

Safety of IACS prior to joint replacement surgery

IACS in the pre-operative joint replacement setting raises concern for prosthetic joint infection (PJI). Guidance from professional societies and federal agencies is vague. The AAOS states that there is limited evidence to suggest that IA injections may have a time-dependent association for increased risk of PJI and that the overall event rate is low.13 The US Centers for Disease Control and Prevention cited low-quality evidence precluding recommendations about preoperative IACS.271 The 2017 ACR/American Association of Hip and Knee Surgeons (AAHKS) Guideline for Perioperative Management did not include comments or recommendations about the timing of preoperative IACS.272 In a survey of AAHKS members, 93% cited that a 3-month interval should be the minimum interval between IACS and joint replacement surgery.34

The literature review and manual search resulted in articles that fell into three principal methodologies: (1) small single-institution cohorts, (2) administrative data reviews, and (3) systematic literature reviews.

Large administrative database analyses—knee

Given the infrequent outcome of PJI, the majority of the patient-derived data came from analyses of large administrative datasets. All knee analyses273–276 were derived from the PearlDiver National Insurance Claim Database, which captures data from Humana, United Healthcare, and Medicare.277 There are variations in (1) the dates of patients sampled, (2) the granularity of the pre-operative IACS window, (3) the definition of infection (superficial vs deep), and (4) postoperative follow-up (6 vs 12 months) across the studies. A single study evaluated the difference between CSI versus hyaluronate injection.274 Three large administrative analyses reported statistically significant increases in PJI risk when total knee arthroplasty (TKR) closely followed an IACS. Infection risk in the comparator group without preceding injection ranged from 1% to 2.7% depending partly on the length of post-TKR observation. All studies reported statistically significant increased multivariate OR or HR for the time periods closest to surgery. Bedard et al reported an increased risk for pre-operative injections done in a 6-month window preceding TKR; however, there was no detectable increased risk when injections were performed after 6 months.275 By contrast, Cancienne et al noted an increased incidence of infection when steroids were injected within 3 months, with no increased risk when the surgery was done 3 months after injection.276 In a study of 76 090 patients, Bhattacharjee et al found that the 0–2 week window for IACS had a significantly increased risk of infection with a trend for increased risk when injections were performed within 2–4 weeks of surgery.273 The 4-week interval was reinforced in a later study by Bains et al.278 They analyzed 9766 patients (4766 had IACS, 5000 without injection) and noted significant risk of surgical site infection when the IACS was done within 4 weeks prior to the TKA. There was no infection risk when the interval was beyond 4 weeks.

For the studies with multivariate analyses,273 274 276 the presence of diabetes, obesity, inflammatory arthritis, or RA all carried significant risk of PJI (regardless of pre-operative IA injection).

Large administrative database analyses—hip

Two separate large administrative analyses focused on the risk of infection after total hip replacement (THR).279 280 Both studies found that the IACS within the 3 months of THR resulted in higher rates of PJI. Both studies noted no increased infection risk for IACS given between 3 and 6 months or between 6 and 12 months.279 280

Three systematic literature reviews were identified (one hip from 2016, one knee from 2014, and one hip or knee from 2014). Charalambous et al concluded that pre-operative IACS was not associated with increased risk of PJI after THR or TKR, citing a non-significant trend for increased risk and lack of a clear mechanism of action for delayed PJI.281 Marsland et al evaluated four level 3 evidence studies and expressed concern about observed trends, but described the data as insufficient to provide recommendations beyond awareness of the risk and optimization of known infection risk reduction peri-operative strategies.282 Pereira et al analyzed eight retrospective studies and a single observational cohort (n=49) and found the level of evidence insufficient to provide a recommendation.283 However, all authors noted the limitations of the studies and data analyzed. A 2023 review and meta-analysis evaluated 11 retrospective matched cohort or case-control studies and concluded that the risk of infection is increased when an IACS is performed within 3 months of THR.284

Intraoperative IA steroid injection—knee and hip

One systematic review identified a total of 12 studies (n=863) comparing the safety and efficacy of IACS administered intraoperatively during TKR/THR.285 Results indicated that patients experienced superior analgesia and less postoperative nausea and vomiting in the immediate postoperative period with no difference in AEs compared with injection with saline. The authors speculated that the safety of intraoperative IACS may be due to the sterile environment of the operating room and careful postoperative monitoring.285 Another study, however, showed an increased rate of infection after intraoperative ICAS in patients who had ankle arthroscopy.286 The authors noted most infections occurred in the 65–79 years age group.

Comments on preoperative IACS and PJI

The literature evaluating PJI after pre-operative IACS is based on administrative databases, underpowered observational cohorts, variability in definition of PJI, and duration of follow-up. Providing IACS during the 3-month pre-operative period may carry increased risk of PJI, especially if done within 2–4 weeks of TKR.273 278 284

For SRs on adverse events, see box 7.