Ultrasound-Guided Procedures in Rheumatology. What Is the Evidence?

REVIEWS

Ultrasound-Guided Procedures in Rheumatology.What Is the Evidence?

Tomas Cazenave, MD,* Carlos Pineda, MD,† Anthony M. Reginato, MD,‡ Marwin Gutierrez, MD,§and On behalf of the Pan-American League Against Rheumatisms (PANLAR) Ultrasound Study Group

Abstract: Ultrasound (US) is a cost-effective, noninvasive, and accessi-ble imaging modality that clinicians use at the point of care to assess dis-ease activity and therapeutic efficacy in different rheumatic conditions.It can play a relevant role in invasive procedures performed by the rheuma-tologist, potentially ensuring a higher degree of accuracy. However,US-guided injections are still underused, and the conventional blind injec-tion the most commonly adopted approach. In this article, we analyze thecurrent evidence supporting the use ofUS-guided procedures, emphasizingcomparative studies between conventional and US-guided procedures andtheir benefits in the daily rheumatological practice.

Key Words: ultrasound, corticosteroids, injections, guided injections

(J Clin Rheumatol 2015;21: 201–210)

U ltrasound (US) has already become a consolidated imagingtool for the rheumatologist. It contributes in daily prac-

tice providing essential information that improves the diagnosticand therapeutic approach in patients with different rheumaticdiseases.1–6Moreover, US is playing a relevant role in the rheuma-tological invasive procedures, ensuring high degree of accuracy inUS-guided interventions.

Diagnostic arthrocentesis and corticosteroid (CS) injectionsof joint and/or periarticular structures play an important role as ad-junct therapeutic procedures in the management of chronic in-flammatory diseases. Their clinical relevance is well underlinedby different rheumatological guidelines.7–12 Studies performedin early rheumatoid arthritis demonstrated that intra-articular CSinjections provided clinical benefits in addition to systemictreatment.13–15 A randomized controlled trial (RCT) comparingmultiple CS joint injections with respect to systemic oral adminis-tration showed that 44% of patients receiving intra-articular injec-tions achieved an American College of Rheumatology 50 responsecompared with 20% of those who received a systemic treatment.16

Anatomical landmark identification using palpation remainsthe most common approach used by most rheumatologists in

From the *Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina;†Musculoskeletal Ultrasound Laboratory, Instituto Nacional de Rehabilitación,México, DF, Mexico; ‡Division of Rheumatology, The Warren Alpert Schoolof Medicine at Brown University, Providence, RI; and §Research Direction,National Rehabilitation Institute,MexicoCity,Mexico; Clinica Reumatologica,Università Politecnica delle Marche Jesi, Ancona, Italy.

PANLAR Ultrasound Study Group: Aliste Marta, Alva Magaly, R. A.Aragón-Laínez, Areny Roser, AudisioMarcelo, Bertoli Ana, Bouffard JoséAntonio, Díaz-Coto José Francisco, Filippucci Emilio, Flores Víctor,Hernández-Díaz Cristina, Hoffman Fritz, Kurslikova María, MendonçaJosé Alexander, Moya Carlos, Mora Claudia, Muñoz-Louis Roberto, PyGuillermo Enrique, Quintero Maritza, Rodríguez Henríquez Pedro,Rosenffet Marcos, Santiago Lida, Sedano Oscar, Solano Carla, UriosteLorena, Ventura Rios Lucio, Villota Orlando, Carmen Ceron, Saaibi Diego,Diaz Mario, Roth Johannes.

The authors declare no conflict of interest.Correspondence: Marwin Gutierrez, MD, Clinica Reumatologica, Università

Politecnica delle Marche, Ospedale “A. Murri,” Via dei Colli, 52 60035Jesi, Ancona, Italy. E-mail: [email protected].

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.ISSN: 1076-1608DOI: 10.1097/RHU.0000000000000242

JCR: Journal of Clinical Rheumatology • Volume 21, Number 4, June 201

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performing diagnostic arthrocentesis andCS or viscosupplementationinjections. However, the accuracy of this conventional approachsometimes may be not acceptable, in particular in small targetssuch as joints or tendons.17

Ultrasound-guided procedures (USGPs) ensure the correctplacement of the needle providing greater accuracy with feweradverse effects. In addition, USGPs may increase the safety ofthe procedure in obese patients (where it is difficult to reachdeep joints) and in damaged joints, avoiding the direct contactbetween the needle and adjacent structures such as nerves, ten-dons, or blood vessels.18,19 The main advantages are the directvisualization of the lesion and surrounding tissues and its rela-tive technical simplicity.

Despite all these advantages, USGPs are not widely used asmight be expected. A recent survey reported that less than 10%of rheumatologists have adopted US to guide their proceduresin most European countries. The primary reasons may be relatedto the lack of proper training and absence of evidence-basedrecommendations.20

In this article, we analyze the evidence supporting the use ofUSGPs, emphasizing recent comparative studies between conven-tional and USGPs and addressing the available data according tospecific anatomical sites.

METHODS

Literature Review Criteria and Search StrategyAll US-relevant literature in the field of US and injections

published in the last 30 years were reviewed. The search for orig-inal articles concerning humans, published between January 1984and September 2014, and referring to the use of US aspirationsand injections was carried out in the PubMed and EMBASE data-bases. The following search terms were used: ultrasound, sonogra-phy, ultrasonography, guided, procedures, injections, aspirations,joints, tendons, shoulder, elbow, wrist, hand, hip, knee, foot,ankle, sacroiliac.

Inclusion and Exclusion CriteriaWe excluded from this review the following types of publica-

tions: articles not published in English, case reports, letters to theeditor that were purely commentary, and/or nonhuman studies.Search results were screened to avoid duplicates. Articles were re-viewed and data extracted and categorized into those assessing thefollowing anatomical targets: shoulder, elbow, wrist, hand, hip,knee, ankle, foot, and sacroiliac (SI) joint. Titles, abstracts, andfull reports of articles identified were systematically screen by 1author (T.C.) with regard to inclusion and exclusion criteria. Ex-tracted data addressed aspects of study design, US methodologyand reproducibility, comparator technique, pathology imaged,and the study findings. The references of published review articleswere screened for additional articles that met our inclusion andexclusion criteria.

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Cazenave et al JCR: Journal of Clinical Rheumatology • Volume 21, Number 4, June 2015

RESULTS

Evidence of USGPs: Analysis byDifferentOutcomesSince the initial published report of US-guided aspiration in

1981,21 an important body of evidence in this topic has beenpublished. Approximately 544 publications were identified inPubMed and EMBASE databases between January 1984 andSeptember 2014. The results of the search strategy are illustratedin Figure 1. Most of these studies have investigated the accuracyfor needle placement of US-guided injection (USGI) versusconventional joint injection and the success rate of US-guidedarthrocentesis. Only few studies have investigated the clinicaloutcome.22–33

US Guidance and Synovial Fluid AspirationIt has been reported that US allows the detection of small vol-

umes of synovial fluid (as small as 7.4 mL in knees34 and 2 mL inthe ankle joints35). Diagnostic arthrocentesis is facilitated by di-rect US visualization of the needle tip, reducing the chances of adry tap or failed aspiration, especially in small or sequestered fluidcollections.36,37 Most of these studies considered the obtaining ofsynovial fluid as successful outcome.

US Guidance AccuracyAccuracy of USGI for injections has been widely investi-

gated as an outcome measure. It is defined by the correct anatom-ical placement of the needle, verified by US or another imagingtool in comparative studies. Table 1 illustrates the principal studiesthat have reported the accuracy of USGI compared with conven-tional needle placement.

A large RCT of CS joint injections in 184 patients showedgreater accuracy of US guidance with respect to conventional ap-proach at multiple sites, including knee (91% vs 82%), shoulder(63% vs 40%), wrist (79% vs 75%), ankle (85% vs 58%), and el-bow (91% vs 64%).30 Similar accuracy of US was found in an-other study comparing US-guided and conventional needleplacement in 63 joints, including the shoulder, knee, ankle, andsmall joints.23 Furthermore, synovial fluid was more frequentlyobtained using US guidance (97% vs 32%).

The accuracyof small joint aspiration, likemetacarpophalangeal(MCP) or proximal interphalangeal (PIP) joints, was also im-proved with US guidance (96% vs 59%).26

Other studies have found similar accuracy for US guidancecompared with computed tomography or magnetic resonance im-aging (MRI) for needle placement and aspiration of joints and softtissue collections at many anatomical regions.38,39

In addition, the accuracy for needle placement provided byUS may also represent an advantage for diagnostic proceduressuch as biopsies. Although US-guided synovial biopsy is notwidely used, less invasive US-guided percutaneous techniques

FIGURE 1. Representation of the search strategy.

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have been developed.19,40,41 A recently published study by Kellyet al41 demonstrated the accuracy of a minimally invasive synovialbiopsy using US guidance in large and small joints, resulting inboth a safe and well-tolerated procedure.

USGI and Clinical OutcomesDespite the extensive evidence supporting the superior accu-

racy of US guidance, there are still insufficient data to ascertainwhether the accuracy of needle placement translates into improvedclinical outcomes. Some authors have reported superior clinicaloutcomes when CS is injected precisely into the target, but thereare also reports indicating that accuracy of needle placementmay not be essential to obtain a satisfactory clinical outcome.42,43

Several studies have demonstrated that improvement in clini-cal outcome is associated with the accuracy of the injection at theshoulder joint.17,30,31 A reduction in joint inflammation (activejoints becoming inactive) was associated with accuracy of injectionin a study by Jones et al,17 with 28 of 54 intra-articular injectionsand 7 of 30 extra-articular injections improving after treatment(P < 0.05). Similarly, Cunnington et al30 found that USGIs weremore accurate than conventional injections and that accurateinjections showed a significant improvement in joint function;however, no significant difference was found between the 2 groupsfor primary outcome measures, including pain and stiffness(although a non–statistically significant trend for alleviation ofpain was observed).30

An RCT that compared US guidance and conventional tech-nique for arthrocentesis and intra-articular CS injections in148 patients reported that USGPs resulted in significant reduc-tions in procedural pain and pain scores at 2 weeks (43% and59%, respectively) and 26% increase in the rate of response(reduction in pain score ≥50%).27 In addition, the accuracy ob-tained with US guidance increased the volume of aspirated fluidby 33.7%. A similar high efficacy was demonstrated in a recentmeta-analysis of USGI of the wrist and clinical outcomes, show-ing a superior short-term improvement in wrist pain with USGPsas compared with conventional injections.44

On the other hand, some studies have failed to show thatgreater accuracy improves outcomes. For example, an MRI-controlled study addressing the accuracy of US-guided SI injec-tions and clinical outcomes did not show any differences betweenaccurate and inaccurate injections.45 Another study of 24 patientswith plantar fasciitis did not find any difference in benefit betweenUSGIs and conventional injections.43

In a systematic review to evaluate the efficacy of USGPscompared with conventional injections, a greater accuracy in theUS-guided group and greater short-term (<6 weeks) clinical im-provement was supported, whereas long-term outcomes werenot different between both groups.33 In aCochrane review, 5RCTsor semi-RCTs were analyzed to assess differences in clinicalimprovement comparing USGPs versus conventional proceduresusing CS in patients with shoulder pain.46 Authors concludedthat despite a moderate difference in efficacy and an evident in-crease in the accuracy favoring USGPs, no relevant superiorityin clinical improvement was demonstrated.

Unfortunately, the safety of USGPs (ie, avoiding damage tothe neurovascular structures) has not been properly evaluated. Asingle-institution study demonstrated the safety of US guidancein 195 therapeutic soft-tissue injections.37 However, at the mo-ment, there are no data showing that USGPs affect the adverseevents, especially procedural infections.30,46 Bloom et al46 foundadverse events in 10% with the USGP method in shoulder com-pared with 16% using conventional approaches.

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TABLE

1.Ac

curacy

ofUSG

Isin

Differen

tAn

atom

icalRe

gion

s

Ana

tomical

Region

Target

Reference

Procedu

reStud

yDesign

AccuracyforNeedlePlacement,%

USG

ICI

Shoulder

Glenohumeraljoint

Cunningtonetal30

Steroidinjection

Randomized,controlled

63.2%

(12of

19)

40.0%

(8of

20)

Subacrom

ialb

ursa

Ruttenetal98

Steroidinjection

Randomized,com

parative

100%

(10of

10)

100%

(10of

10)

Acrom

ioclavicular

joint

Borbasetal52

Dye

injection

Cadaveric,com

parative

90%

(36of

40)

70%

(28of

40)

Bicepstendon

sheath

Hashiuchi

etal53

Steroidinjection

Randomized,com

parative

86.7%

(13of

15)

26.7%

(4of

15)

Elbow

Hum

eroulnar

joint

Cunningtonetal30

Steroidinjection

Randomized

controlled

91%

(10of

11)

64%

(7of

11)

Hum

eroulnar

joint

Kim

etal60

Contrastagent

injection

Randomized,com

parative

100%

(40of

40)

77.5%

(31of

40)

Wrist

Radiocarpaljoint

Luz

etal29

Steroidinjection


90%

(27of

30)

90%

(27of

30)

Radiocarpal,m

idcarpal,

radioulnar

joints

Cunningtonetal30

Steroidinjection


79%

(11of14)

75%

(12of

16)

Radioulnar

Nam

etal99

Steroidinjection


100%

(28of

28)

75.8%

(22of

29)

Hand

Metacarpophalangealjoint

Razaetal26

Jointlavage

Com

parative

100%

(27of

27)

80%

(4of

5)Proxim

alinterphalangealjoint

Razaetal26

Jointlavage

Com

parative

92.3%

(24of

26)

50%

(6of

12)

Finger

flexor

tendon

sheath

Lee

etal64

Dye

injection

Cadaveric,com

parative

70%

(14of

20)

15%

(3of

20)

Hip

Coxofem

oraljoint

Smith

etal25

Contrastagent

injection

Fluoroscopyconfirmed

97%

(29of

30)

N/A

Knee

Femorotibialjoint

Balintetal23

Fluidaspiratio

nCom

parative

94.7%

(18of

19)

40.%

(4of

10)

Femorotibialjoint

Cunningtonetal30

Steroidinjection

Randomized

controlled

91.4(32of

35)

81.8

(27of

33)

Femorotibialjoint

Imetal81

injection

Randomized,com

parative

95.6%

(43of

45)

77.3%

(34of

44)

Ankle

Tibiotalarjoint

Cunningtonetal30

Steroidinjection

Randomized

controlled

85%

(11of

13)

58%

(7of

12)

Tibiotalarjoint

Wisniew

skietal89

Dye

injection

Cadaveric,com

parative

100%

(20of

2085%

(17of

20)

Sinustarsijoint

Wisniew

skietal89

Dye

injection

Cadaveric,com

parative

90%

(18of

20)

35%

(7of

20)

Peronealtendon

sheath

Muiretal100

Dye

injection

Cadaveric,com

parative

100%

(20of

20)

60%

(12of

20)

Foot

Tarsom

etatarsaljoint

Khoslaetal90

Dye

injection

Cadaveric,com

parative

64%

(18of

28)

25%

(7of

28)

Sacroiliacjoint

Sacroiliacjoint

Klauser

etal96

Needleplacem

ent

Cadaveric,com

puted

tomographyconfirmed

80%

(16of

20)

N/A

Sacroiliacjoint

Pekkafahlietal97

Contrastagent

injection

Fluoroscopyconfirmed

76%

(46of

60)

N/A

Sacroiliacjoint

Hartung

etal45

Steroidinjection

MRIconfirmed

40%

(8of

20)

N/A

CIindicatesconventio

nalinjection;

N/A,not

applicable.

JCR: Journal of Clinical Rheumatology • Volume 21, Number 4, June 2015 Evidence of US-Guided Injections

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Evidence of USGPs by Anatomical Target

ShoulderThe shoulder is a complex joint where many structures can

be involved. This may affect accuracy of conventional injections.Eustace et al31 reported that only 29% (4 of 14) of subacromialand 42% (10 of 24) of glenohumeral joint injections were accu-rately placed using the conventional technique. Ultrasound-guided injections of the glenohumeral joint have shown to havesimilar accuracy compared with fluoroscopy-guided injections.47

Some studies have demonstrated improvement in shouldersymptoms irrespective of needle correct placement,48 whereasothers have reported improved clinical outcome with image-guided injections.49

Two relevant RCTs have compared USGIs versus conven-tional injections of the shoulder. Both studies included pain(assessed by visual analog scale [VAS]) and function (assessedby Constant score or Shoulder Function Assessment scale) asefficacy outcomes.

The first study, published by Naredo et al,32 compared short-term clinical response to CS USGPs versus conventional injec-tions in 41 patients with painful shoulder. Patients were random-ized to receive either a conventional subacromial injection(group 1, n = 20) or a USGI of 20 mg triamcinolone (group 2,n = 21). Six weeks after injection, the USGP group showed a sig-nificantly greater improvement compared with the conventionalgroup (mean pain VAS score change: 34.9 for group 2 vs 7.1 forgroup 1, P < 0.001; and mean shoulder function score change:15 for group 2 vs 5.6 for group 1, P = 0.012). Only 30% of theblinded injections were found to be accurately placed within thesubacromial bursa.

A similar study by Ucuncu et al50 included 60 consecutivepatients with shoulder pain randomly assigned to receive triamcin-olone either by conventional injection (n = 30) or US guidance(n = 30). Patients were evaluated at baseline and at 6 weeks offollow-up. Six weeks after injection, the VAS for pain and the con-stant score for joint function showed a significant improve-ment in USGP group compared with the blinded group (meanpain VAS score decrease: 4.0 ± 1.7 for USGI vs 2.2 ± 0.9 for con-ventional, P < 0.05; mean constant score change: 32.2 forUSGI vs 12.2 for conventional, P < 0.05). In both studies, moreadverse effects (all mild, including slight increase in pain and skinpeeling after injection) were reported with conventional injec-tions, although the difference was not statistically significant.In a similar RCT, Lee51 evaluated the clinical effect of intra-articular US guidance compared with the conventional approachfor the treatment of adhesive capsulitis. After 2 weeks, improve-ments in pain intensity, range of motion, and shoulder functionscore were significantly greater in the USGP group comparedwith the conventional injection group (P < 0.05).

Other anatomical targets of the shoulder have been studiedwithUSGPs. Ultrasound guidance injections of the acromioclavicularjoint has shown to improve accuracy (USGP 90% vs conventional70%).52 In a randomized trial, Hashiuchi et al53 compared aUSGPs versus conventional technique in 30 patients with teno-synovitis of the biceps tendon and found that the USGPs re-sulted in 86.7% inside the tendon sheath compared with only26.7% of the conventional group.

In a systematic review by Soh et al,54 the efficacy of USGPsof the shoulder showed greater improvement in both VAS for pain(mean difference, 2.23; 95% confidence interval [CI], 1.27–3.18)and shoulder function (standardized mean difference [SMD],1.09; 95% CI, 0.61–1.57) compared with conventional. A similargain in efficacy was found in another systematic review by Sageet al,55 demonstrating a statistically significant difference in favor



of the USGPs for pain improvement at 6 weeks (SMD, 1.03; 95%CI, 0.12–1.93; P = 0.03), although the authors concluded that thissmall difference might not be clinically relevant.

Finally, as previously mentioned, a Cochrane review (includ-ing 5 studies and 290 participants) reported no significant differ-ences between groups with respect to reduction in shoulder painat 1 to 2 weeks (SMD, −1.44; 95% CI, −4.14 to 1.26) or functionat 1 to 2 weeks (SMD, 0.95; 95% CI, −1.29 to 3.20) or 6 weeks(SMD, 0.63; 95% CI, −0.06 to 1.33).46 Although there was asignificant difference between groups with respect to reductionin pain at 6 weeks favoring a USGP (SMD, −0.80; 95% CI,−1.46 to −0.14), there was considerable statistical heterogeneity,and after removing inadequate trials, the difference was no longersignificant.

ElbowEvidence regarding USGPs at the elbow is limited, with a

small number of studies mainly focused on periarticularpathologies.56–60 Although there is no RCT assessing efficacy atthe elbow, a study reported a greater accuracy for intra-articularUSGI (91%) versus conventional injection (64%).30 A similar de-gree of accuracy was found in another study including patientswith degenerative involvement of the elbow (USGP 100% vsconventional 77.5%).60

WristSeveral studies have included the wrist as target joint for

USGPs. Contradictory results have been found between USGPsand conventional procedures.27,29,30,61 In a double-blind RCT ofpatients with inflammatory arthritis comparing USGPs versusconventional injections, 30 wrists (30 of a total of 184 joints stud-ied [16%]) were injected with CS (14 by USGIs and 16 conven-tional injections).30 Patients were followed up longitudinally for2, 6, and 12 weeks after injection. Therewas no statistically signif-icant difference between the 2 groups for any of the major effi-cacy outcomes. Ultrasound-guided procedures showed a similaraccuracy in the wrist (US 79% vs conventional 75%) and a greateraccuracy when considering the total number of joints (US 83% vsconventional 66%; P = 0.01).

In another randomized double-blind controlled study by Luzet al,29 60 patients with rheumatoid arthritis and wrist synovitiswere included. Patients were randomly assigned to receive CSby USGPs (n = 30) or conventional injection (n = 30) andfollowed up at 1, 4, 8, and 12 weeks after the procedure. No statis-tically significant difference was seen between the 2 groups inaccuracy or efficacy outcomes (VAS for pain, Health AssessmentQuestionnaire).

A recent meta-analysis compared changes in wrist pain fol-lowing intra-articular CS using USGI versus conventional injec-tion in patients with inflammatory arthritis and osteoarthritis(OA).44 Main outcomes were mean change in wrist pain (esti-mated by VAS), and minimal clinically important improvementwas defined as VAS reduction of 20% or greater, from baselineto 1 to 6 weeks of follow-up. Four comparative studies were in-cluded in the analysis. Mean change in VAS in the 4 comparativestudies ranged from 2.7 to 5.7 in the conventional arms and from3.8 to 5.8 in USGP arms. The difference in mean VAS reductionranged from 0.2 to 1.3, with a combined estimate of 1.0 (95%CI, 0.3–1.7). Odds ratios (ORs) for achieving minimal clinicallyimportant improvement ranged from 1.0 to 12.4, with a combinedOR of 3.2 (95% CI, 1.2–8.5) in favor of the US guidance.

Furthermore, US guidance has shown to be useful in patientswith carpal tunnel syndrome. In a study by Makhlouf et al62 com-paring conventional technique with a USGP of the carpal tunnel,



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US guidance resulted in superior clinical outcomes, reducing painscores and increasing therapeutic duration and the responder rate.

HandFew studies have assessed USGPs at the small joints of the

hand. In the multijoint-targeted studies evaluating the efficacy ofUSGPs, the small joints of the hand usually represent a minorityof the joints assessed (3%–5.5%).27,61 As demonstrated by Razaet al,26 accuracy for intra-articular needle placement improveswhenUS guidance is used in small joints of the hand. This study fo-cused on MCP and PIP joints showed an accuracy of 59% in theconventional group (6 of 12 PIP and 4 of 5 MCP joints) versus96% in the USGP group (24 of 26 PIP and 27 of 27 MCP joints).In a prospective study by Di Sante et al63 including 31 patientswith trapeziometacarpal OA treated with USGI of hyaluronate,a statistically significant pain reduction was observed at 1 and3 months after the end of treatment (P < 0.01) but not at6 months of follow-up (P = 0.6). Other studies evaluated the roleof USGPs in tendon involvement at the hand.64–70 A cadavericstudy evaluated the accuracy of the US versus conventionalapproach when injecting dye in the flexor tendon sheet in 40 fin-gers.64 Results showed an accuracy of 70% for USGPs and 15%for conventional procedures (P = 0.001). However, in 30% of con-ventional procedures and none of the USGPs, the dye was ob-served inside the tendon, which could be considered an adverseoutcome. The efficacy of USGPs with CS in patients with triggerfinger can be high, as reported by Callegari et al,65 who found a to-tal resolution of symptoms in almost all subjects treated (93.3%)after 6 months. In addition, US guidance has been reported tobe useful for the treatment of de Quervain tenosynovitis.66,67 Bet-ter efficacy outcomes have been reported in USGPs comparedwith conventional technique, and some authors attribute thesefindings to the capacity of US to detect subcompartments of thetendon sheath. A randomized study including patients with deQuervain tenosynovitis reported a superior reduction of painusing US guidance compared with conventional injection after4 weeks (P = 0.0007).66

An original study published by Di Geso et al68 evaluated30 patients with clinical signs suggestive of tenosynovitis. In21 patients, tenosynovitis was confirmed and graded by US scor-ing (11/21 were finger flexor tenosynovitis), and CS USGP wasperformed. After 2 weeks of follow-up, a reduction in all clinicaland sonographic scorings was found in the USGPs group.

HipInjections of the hip can be challenging for the physician,

as non-USGIs are often inaccurate.71 Therefore, the utility ofa USGP for the hip has been investigated in severalstudies.25,38,71–76 Smith et al25 evaluated 30 hip USGPs usingfluoroscopic visualization to verify intra-articular needle place-ment. Overall, 97% of sonographically placed needles were accu-rately placed. In a prospective study conducted to compare theshort-term effectiveness of US and fluoroscopy-guided CS injec-tions, Furtado et al74 reported comparable improvement in func-tion and pain outcomes after 4 weeks in both groups. In anotherprospective trial, Micu et al75 evaluated 40 patients with hip OAand synovitis detected by US. After 1 USGI of CS at baseline, pa-tients were followed up at 1 and 3 months, assessing VAS forwalking pain intensity, Lequesne index for function, and repeatedUS examination to monitor synovitis score. A group of patientswho refused to be injected was included as control subjects. After1 and 3 months, walking pain was significantly reduced comparedto baseline (P < 0.001) and had high correlation with Lequesneindex. Synovial hypertrophy was reduced in 75% of the hips after



1 and 3 months versus baseline (P < 0.001). In the control group,no difference was found in pain, function, or synovitis at 3 monthscompared to baseline (P > 0.05). Atchia et al76 assessed efficacyof a single USGP in 77 patients with hip OA after being random-ized to 1 of 4 groups: (1) standard care (no injection), (2) normalsaline injection, (3) hyaluronic acid, or (4) methylprednisoloneacetate injection. At baseline and follow-up visits, clinical mea-surements included WOMAC (Western Ontario and McMasterUniversities Arthritis Index) and pain by numerical rating scale.After 1 week, large effect sizes were found (numerical ratingscale pain: 1.5, WOMAC pain: 1.9, and WOMAC function:1.3). The CS group obtained significantly more responders thandid the other groups (CS: 74%, saline: 21%, hyaluronic acid:11%, and no injection: 10%; P < 0.001). Corticosteroid responsewas maintained over 8 weeks, and synovitis was a significant pre-dictor of response at weeks 4 and 8 (P < 0.05; week 4 OR, 16.7;95% CI, 1.4–204).

Ultrasound guidance may also contribute to therapeuticeffectiveness in complex anatomy regions such as the greatertrochanteric area. McEvoy et al77 documented the therapeutic re-sponse of USGI into the greater trochanteric bursa as opposedto the subgluteus medius bursa in 65 patients with greater trochan-teric pain syndrome, reporting a statistically significant differencein pain reduction when the greater trochanteric bursa was injec-ted (P < 0.01) by US guidance.

KneeThere are several USGP studies that have evaluated the

knee.30,78–84 There is extensive evidence provided by controlledtrials that supports the use of US guidance to obtain improvedclinical outcomes.27,61,79,85 In a systematic review that comparedUSGPs and conventional procedures of the knee, Berkoff et al86

reported a better result with US (95.8% vs 77.8%,P < 0.001), withan OR of 6.4 (95% CI, 2.9–14).

Sibbitt et al27 conducted an RCTof 148 painful joints (62 of148 were knees [41.9%]) comparing CS USGPs versus conven-tional injections and found that the USGPs resulted in a reductionin procedural pain by 43% (P < 0.001), a 59% reduction in abso-lute pain scores after 2 weeks (P < 0.001), a 75% reduction in sig-nificant pain (defined as reduction of VAS ≥50 mm; P < 0001), a26% increase in the responder rate (defined as reduction in VAS≥50% from baseline P < 0.01), and a 62% reduction in the nonre-sponder rate (defined as reduction in VAS score <50% from base-line; P < 0.01).27 Ultrasound also increased detection of effusionby 200% and volume of aspirated fluid by 337%. In a subsequenttrial, Sibbitt et al61 evaluated 244 joints (85 of 244 = 34.8% wereknees) that were randomized to either conventional procedure or aUSGP. Compared with anatomical guidance, the USGPs reducedinjection pain by 81% (P < 0.001), decreased pain scores by 35%after 6 months (P < 0.02), and increased therapeutic durationby 32% (P = 0.01). The same group reported the results of anRCT including 94 knees with OA randomly assigned to receiveCS by either a USGP or conventional procedure evaluating theclinical outcomes after 6 months of the procedure.79 Ultrasound-guided procedures were significantly less painful than the conven-tional technique, causing 48% less absolute procedural pain (nee-dle introduction pain) and 58% fewer individuals with significantprocedural pain as well as 91% less injection pain (all P < 0.01).With regard to efficacy, the USGPs resulted in a 36% increasein therapeutic duration (P = 0.01) and 42% less knee pain at2 months (P < 0.03) but no difference at 6 months. Moreover, ina cost-based analysis, this study showed a 13% reduction ($17)in cost per patient per year and a 58% ($224) reduction in costper responder per year for a hospital outpatient (P < 0.001). Morerecently, Sibbitt et al85 conducted another RCT to compare clinical

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outcome ofUS-guided aspirationversus conventional arthrocentesisin 64 palpably knee effusions. Ultrasound-guided procedures re-sulted in 48% less procedural pain (VAS; conventional: 5.8 ±3.0 cm, USGP: 3.0 ± 2.8 cm; P < 0.001), 18.3% increased vol-umes of aspirated synovial fluid (conventional: 12 ± 10 mL,USGP: 34 ± 25 mL, P < 0.0001), and 46% less pain after2 weeks of follow-up (VAS for pain; conventional: 2.8 ± 2.4 cm,USGP: 1.5 ± 1.9 cm; P = 0.034).

In addition, some studies have highlighted the potentialrole for US guidance to treat Baker cysts, showing improved clin-ical outcomes and effectiveness in aspiration of fluid. Di Santeet al87 prospectively evaluated the effectiveness of 26 US-guidedBaker cyst aspiration followed by CS injection in patients withOA of the knee, reporting a significant difference after 4 weeksin WOMAC for pain (P <0.0001) but not for joint stiffness(P = 0.7239) and disability (P = 0.6318). In another RCT by thesame group that compared USGI and aspiration of Baker cystsversus physical therapy (horizontal therapy) or the combinationof both, significantly better outcomes for pain, WOMAC, and ef-fect duration were obtained in the USGP groups compared withphysical therapy alone.88

Ankle and FootFewer studies concerningUSGPs have been performed in the

ankle and foot; most of these studies have been carried out in ca-daver specimens with lack of efficacy data. A study on 20 cadav-eric ankles reported a superior accuracy of a USGP comparedwithconventional (USGP: 100% and 95% vs conventional: 90% and35% for tibiotalar and sinus tarsi joints, respectively).89

Randomized studies to evaluate efficacy that have includedtibiotalar joints show controversial results in clinical outcomes be-tween conventional procedures and USGPs, although the anklerepresented a minority of the joints studied (2.7% to 13%).27,30,61

Accuracy also seems to be superior using US guidance atthe midfoot joints.90 In a retrospective study, Drakonaki et al91

assessed the clinical outcomes of 59 patients with midfoot joint

FIGURE 2. Representative images of USGIs. A, Knee. Proliferative synoviavoiding the synovial proliferation (*) and performing an accurate aspirainflammation area in between the extensor tendons (e) and the lunate bois correctly placed in the area of synovitis. The joint cavity widening in efemoral bone; l, lunate bone; m, metacarpal bone; mt, metatarsal bone.



degenerative changes treated with USGI of CS, demonstratinga positive therapeutic effect (as partial or complete resolutionof pain) in 78% and 57% of the patients at 2 weeks and at3 months, respectively.

In an original study conducted by Kang et al,92 21 patientswith acute gout attack involving the first metatarsophalangealjoint were enrolled and treated with USGI of CS. After 2 days,the reductions of mean VAS scores in pain, general disability,and walking disability were 48 ± 27, 35 ± 26, and 39 ± 26 mm,respectively.

Given the accuracy of USGPs and the consequent capacity toavoid the misplacement of the drug, there are emerging studiesevaluating US guidance in the treatment of heel enthesopathy.Huang et al93 performed an interesting trial to evaluate the effi-cacy of USGI of etanercept in patients with ankylosing spondylitisand refractory Achilles enthesitis. Twelve patients were enrolled(5 used a local USGP of etanercept and 7 received USGP ofCS). Pain, activity, and functional measures were recorded atbaseline and at 2, 4, 8, and 12 weeks after the treatment. Resultsshowed a significant improvement of all outcome measures atall visits with no differences between the 2 treatment arms. Ferreroet al94 described the improvement of 30 Achilles tendons treatedwith an intratendinous USGPs of platelet-rich plasma. After6 months of follow-up, pain decreased and functional measuresimproved, and in addition, US evaluation revealed a reduction ofhypoechoic areas (P < 0.01) associated with a widespread im-provement of fibrillar echotexture of the tendon and reducedhypervascularity evaluated by power Doppler.

At the plantar fascia, USGP performance was illustrated in2 trials evaluating efficacy. In the study conducted by Kane,43

14 heels with plantar fasciitis were randomized to USGI: 10 toconventional injection and 4 heels were not injected. The USGPsresulted in significant mean improvements in pain after 13 weeksof follow-up. There was no significant difference in the responserate following CS injection by either modality (US = 13/14, palpa-tion = 8/10). Following injection, the mean thickness of the plantarfascia decreased from 5.7 ± 0.3 mm to 4.65 ± 0.4 mm (P < 0.01).

tis. Note as the needle (arrow) is justly placed in the area of fluidtion. B, Wrist, synovitis. The needle (arrow) is placed in thene (l). C,MCP joint. D,Metatarsophalangeal joint.Note as the needleach target measured 4.2 and 2.2, mm respectively. f Indicates



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In another study conducted by McMillan et al,95 including82 patients with plantar fasciitis randomized to receive USGI ofCS or a saline solution, results showed a significant improvementin pain favoring the CS treatment group, which persisted up to3 months of follow-up.

Sacroiliac JointThere is an increasing interest in the applicability of US for

SI assessment; however, few studies of USGPs of the SI joint havebeen published. Accuracy for an intra-articular USGP performedin cadaveric SI joints reaches up to 90%, depending on the siteinjected.96 Pekkafahli et al97 conducted a study of a USGP includ-ing 60 SI joints of patients with sacroiliitis reporting an accuracyof 76% (46/60) as confirmed by fluoroscopy. Hartung et al45 con-ducted an interesting study to assess accuracy and clinical out-come of SI USGI with CS in patients with sacroiliitis. Clinicaloutcome of the USGPs was analyzed in relation to its accuracyverified by MRI. Despite US guidance, only 8 (40%) of 20 injec-tions were exactly positioned into the joint space. Furthermore,there were no significant differences in the clinical outcomes be-tween accurate or inaccurate groups, with a similar pain reliefobserved in both groups 24 hours and 28 days following theprocedure. These results contrast with those reported by Klauseret al,96 who performed a study including 10 patients withsacroiliitis treated with a CS USGP. All USGIs were correctlyplaced inside the joint (100% of accuracy) and with a mean painrelief of 8.6 points (0–10 by dolorimetry scale) after 3 monthsfrom baseline. It should be noted that the most likely explanationfor this discrepancy in accuracy and efficacy results could be re-lated to different frequencies of ankylosis of the SI joints amongpatients, considering that the presence of ankylosis may reducethe success of intra-articular placement of the needle.

DISCUSSIONSince US was introduced in the rheumatology field, it has

been used for diagnostic, monitoring, and therapeutic purposes.Ultrasound guidance applied to arthrocentesis and CS injectionsprovides simplicity and accuracy for the physician. Ultrasound-guided procedures are based on the fact that needles arehyperechoic and thus can readily be detected. The ability to placethe needle accurately within the anatomical target is important toachieve success in fluid aspiration and therapeutic injections.

In recent years, increased efforts have been placed to deter-mine whether US guidance provides any additional benefits whencompared with conventional approaches. Researchers’ workresulted in a variety of studies of different quality and level ofevidence. Most of these studies have pointed out the accuracyof US guidance in needle placement and the success rate inarthrocentesis, whereas only a few have investigated clinicaloutcomes.22–33

Much of the data reported by comparative trials demon-strated greater accuracy when US guidance is used, and thisadvantage improved the success rate of arthrocentesis.27,30,31

Figure 2 shows a pictorial representation of the accurate place-ment of the needle in different anatomical areas. Despite this, itis still not clear whether this gain in accuracy translates into betterclinical outcomes. Regarding efficacy of USGPs, data comingfrom RCTs are contradictory. For example, some RCTs havefound a superior short-term efficacy to reduce pain whenUS guid-ance is used.27,35,50,78,84 Furthermore, in 3 RCTs that comparedprocedural pain, USGIs were reported to be less painful than con-ventional injection.27,78,84 However, other studies, including sys-tematic reviews and meta-analysis, did not find substantialefficacy differences when comparing both techniques.30,43,46,97



Some general limitations of the studies included in this re-view should be noted, such as the small number of patients in-cluded, short follow-up period, heterogeneity in their design, andthe absence of control subjects for a possible placebo effectfrom the US procedure itself that may explain the lack of betterclinical outcomes.

An important feature of our analysis is the existing evidenceaccording to the different anatomical areas. Our approach revealedan imbalance of the available data at the different anatomicalregions, with more RCTs and better-quality studies focusedon shoulder, knee, and hip joints. Therefore, there is a lack ofevidence of USGPs in small joints, tendons, and periarticularstructures.

One limitation of our review is the absence of data about therole of USGPs in the entheses and carpal tunnel syndrome. Thescarce data available and the lack of the search criteria for this re-view were mandatory for not including these topics. It is remark-able also that, despite the availability of 2 methods of guiding theneedle with US: direct (with total visualization of the needle dur-ing the procedure) and indirect method (where US is used only toselect the point of access), there are no studies comparing resultsbetween these different methods. Future studies should be ori-ented in this way.

In conclusion, although several studies have addressed thatUS may help the rheumatologist in interventional procedures, itis clear that further studies are needed to determine the degreeof benefit, especially long-term studies regarding efficacy andclinical outcomes that could be achieved with the accuracy ofUS guidance procedure.

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Ultrasound-Guided Procedures in Rheumatology. What Is the Evidence?

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