Med. J. Cairo Univ., Vol. 83, No. 2, June: 13-21, 2015 www.medicaljournalofcairouniversity.net

Ultrasonographic Evaluation of Hand and Wrist Tendons in Patients with Rheumatoid Arthritis HALA I. ELGENDY, M.D.*; HATEM M. ELAZIZI, M.D.** and RASMIA M. ELGOHARY, M.Sc.* The Departments of Internal Medicine* and Radiodiagnosis**, Faculty of Medicine, Cairo University

function impairment and eventually permanent disability [2] .

Abstract Introduction: To evaluate hand and wrist tendons involvement in rheumatoid arthritis patients (RA) and to determine the factors that are potentially associated with more frequent tendon involvement.

Tenosynovitis is one of the key features and is likely to be the primary event of the RA [3] . Long standing tenosynovitis may result in tendon damage either by synovial proliferation or by bone attrition resulting in tendon rupture with consequent disability [4] .

Material and Methods: Thirty patients with RA and 20 healthy controls matched by age, sex and body mass index (BMI) were subjected to: Full history, thorough clinical examination, radiographic assessment and ultrasound assessment of tendons at the level of fingers and wrists. This study was performed on patients attended the rheumatology & immunology outpatient clinic, internal medicine department of Kasr Al-Ainy Hospital, Cairo University, during (20112013).

Ultrasonography (US) allows for a sensitive detection of periarticular soft-tissue involvement including tendon inflammation and damage [5] . The Ultrasonography is quick, easy to perform, and safe [6] . Moreover, US allows a dynamic multiplanar information that helps to make an accurate diagnosis and also guides interventional diagnostic and/or therapeutic procedures [7] .

Results: Tenosynovitis/tendonitis was found in at least one tendon in 15 (50%) of 30 patients. Tendon damage was found in at least one tendon in 6 (20%) patients. Global disease activity and local joint synovitis were significantly related to inflammation of hand & wrist tendons ( p-value 3.2 and ≤ 5.1) High activity (DAS 28 >5.1)

0 1 (3.3) 11 (36.7) 18 (60)

Total joint damage score Total erosion score JSN score

25 (83.3) 23 (76.7) 21 (70)

IQR Interquartiles ranges. BMI Body massindex. HAQ Health associated questionnaire. Anti-CCP: Anti cyclic citrulinated peptide.

Mean

9.07 ± 12.8 3.67 ± 4.7 5.40± 8.5

4.5 (1-10) 2 (0.75-4.5) 2.5 (0-6)

ESR : Erythrocyte sedimentation rate. DAS 28 : Disease activity score-28. JSN : Total joint space narrowing score.

The studied group showed different degrees of disease activity as defined by DAS 28-ESR (mean 5.3 ± 1.2), with none of our patients in remission. The studied group had generally mild levels of functional impairment, as measured by the modified HAQ (mean 0.7 ±0.6). The majority of patients [25 of 30 (83.3%)] had evidence of radiographic joint damage, as assessed using the Van der Heijdemodified Sharp scoring method. At time of study, 36.66% of the cohort currently taking corticosteroids (mean dose 6.9 ± 2.3mg/day), 73.3% was currently taking DMARDs, 40% of them were taking one DMARD and 33.33% were

taking combination DMARD therapy. DMARD included; methotrexate (50%, mean dose 17.0 ±6.1 mg/day), leflunomide (30%), sulfasalazine (3.3%), etanercept (3.3%). Three patients received no drugs. Distribution of tendon involvement in different tendon groups: Tenosynovitis/tendonitis was found in at least one tendon in 15 (50%) of 30 patients. Tendon damage was found in at least one tendon in 6 (20%) patients. At the level of hands, flexor tenosynovitis (Fig. 1) was found in 7 of 240 (2.9%) tendons, while extensor tenosynovitis was found in 10 of 240 (4.2%) tendons.

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Ultrasonographic Evaluation of Hand & Wrist Tendons

Fig. (1): Finger Flexor Tenosynovitis. Finger flexor tendon at the level of metacarpophalangeal (MCP) joint. Sonographic images, obtained in longitudinal (A) and transverse (B) scans, show peritendon effusion and synovial hypertrophy taking Doppler signals.

The most frequently involved tendons were the extensor and flexor tendons of the 5 th finger. The flexor tendon damage was found in 2 of 240 (0.8%) tendons, while extensor tendon damage was found 8

(A)

6.7%

in 3 of 240 (1.3%) tendons. The most frequently involved tendons were the extensor tendon of the 5 th finger and the flexor tendon of the 4 th finger. The distribution of US findings is reported in Figs. (2,3). 10

10%

(B)

4

%

%

6 3.3%

5 3.3%

3.3%

1.7%

2

0%

0%

0

0 FFT2

FFT3

FFT4

FFT5

FET2

FET3

Synovial effusion

Synovial hypertrophy

Peritendon PD

Intratendon PD

FET4

FET5

Tenosynovitis/tendinitis Fig. (2): Distribution of US findings indicative of finger tendon inflammation. (A) Flexor tendons at finger level. (B) Extensor tendons at finger level. FFT: Finger flexor tendon, FET: Finger extensor tendon, PD: Power Doppler.

4

(A)

5

3.3%

5%

(B)

4

%

%

3 2

2 1 0%

0%

0%

0%

0%

0%

0

0 FFT2

FFT3

FFT4

FFT5

FET2

FET3

Echotexture derangement

Diffuse swelling

Focal swelling

Tendon damage

FET4

FET5

Fig. (3): Distribution of US findings indicative of finger tendon damage. (A) Flexor tendons at finger level. (B) Extensor tendons at finger level.

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Hala I. Elgendy, et al.

At the level of the wrist, flexor peritendonitis was found in 4 of 180 (2.2%) tendons, while extensor tenosynovitis was found in 12 of 360 (3.3%) tendons. The most frequently involved tendons 6

were the extensor carpi ulnaris (ECU) and flexor digitorum. The extensor carpi ulnaris tendon was the only tendon affected by damage. The distribution of US findings is reported in Fig. (4). 10

(A)

5%

(B)

10%

8 4 %

%

6 1.7%

2

3.3%

4

3.3% 1.7%

1.7%

2 0%

0%

0

0 PCR

FD

FPL

CET1 CET2 CET3 CET4 CET5 CET6

Peritendon effusion

Intratendon Doppler signal

Peritendon synovial (hypertrophy SH)

Tenosynovitis/tendinitis

Peritendon Doppler signal Fig. (4): Distribution of US findings indicative of tendon inflammation at wrist level. (A) Flexor tendons at wrist level. (B) Extensor tendons at wrist level. CET: Compartment extensor tendon.

Analysis of factors that may influence the involvement of tendons of hands and wrist in RA patients: The relation between US findings of tendon involvement and disease activity as assessed by DAS 28-ESR and the corresponding joint US synovitis score is reported in Table (3). The relation between US findings of tendon

involvement and radiographic joint damage is reported in Table (4). Table (5) demonstrates other factors that are potentially associated with more frequent tendon involvement in RA patients. Anti-CCP was the only variable associated ( p=0.049) with the tendon inflammation. On the other hand, the dominant hand was the only variable associated with the tendon damage (p=0.001).

Table (3): Relation between tendon involvement and disease activity. Tenosynovitis/tendinitis

Tendon groups

Tendon damage

Coefficients

t

p-value

Coefficients

t

p-value

All Tendons

DAS-28

.017

3.397

.001

.001

.472

.637

Finger tendons

Finger SH score Finger PDU score

.021 .051

2.268 4.168

.024 .000

.004 .007

.852 1.057

.394 .291

Wrist tendons

Wrist SH score Wrist PDU score

.023 .015

3.213 1.714

.001 .087

.003 .003

1.827 1.390

.068 .165

DAS 28: Disease activity score-28. SH: Synovial hypertrophy. US: Ultrasound.

PDU: Power Doppler ultrasonography.

Table (4): Relationship between tendon involvement and radiographic damage. Tenosynovitis

Tendon groups

Tendon damage

Coefficients

t

p-value

Coefficients

t

p-value

Finger tendons

Total erosion score Total JSN score

–3.212E-5 –5.416E-5

–.018 –.053

.986 .958

.003 .002

3.085 3.160

.002 .002

Wrist tendons

Total erosion score Total JSN score

.002 .002

1.328 1.851

.185 .065

.000 1.605E-5

–.573 .072

.567 .943

JSN: Joint space narrowing.

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Ultrasonographic Evaluation of Hand & Wrist Tendons

Table (5): Multiple regression model for analyzing the factors influencing tendon involvement in RA patients. Independent variables Sex Age BMI Hand Duration Work RF Anti-CCP

Tendon inflammation

Tendon damage

Coefficients

Std. Error

t

Sig.

Coefficients

Std. Error

t

Sig.

–.037 .000 –.001 .011 –.001 –.013 –.020 .036

.025 .001 .001 .012 .001 .015 .016 .018

–1.495 –.444 –.744 .941 –1.253 –.831 –1.232 1.968

.135 .657 .457 .347 .211 .406 .218 .049

–.015 –.001 .000 .023 .000 -9.254E -5 .013 –.013

.014 .000 .001 .007 .001 .009 .009 .010

–1.042 –1.851 .401 3.273 .226 –.010 1.427 –1.255

.297 .064 .688 .001 .821 .992 .154 .210

BMI: Body mass index. RF: Rheumatoid factor. Anti-CCP: Anti-cyclic citrulinated peptide.

Discussion This study is one of few studies providing data on distribution of US findings with respect to tendon involvement in Egyptian RA patients, obtained with a high frequency probe and includes tendons at the level of fingers and wrists. Our study showed more tenosynovitis of finger extensor tendons (4.2%) compared to finger flexor tendons (2.9%). This was surprising because the finger flexor tenosynovitis had previously been shown to be more common than finger extensor tenosynovitis in RA patients. This data, however, refer to early untreated RA patients as reported by Wakefield et al., [2] who conducted their study on 50 patients with early untreated RA. They found finger flexor tenosynovitis in 57 (28.5%) of 200 joints and finger extensor tenosynovitis in 14 (7%) joints. Backhaus et al., [18] conducted their study on established RA patients and reported tendon sheath widening in 21 % of finger flexor tendons and 5% of finger extensor tendons. However they used a low frequency probe (7.5 MzH) that poorly differentiate extensor peritendon inflammatory changes from the surrounding joint synovitis, and this may explain the low prevalence of periextensor tendon disease in their study. However larger samples were needed for a final conclusion. Our results showed relatively lower incidence of tenosynovitis at the level of hands and wrists when compared with the study by Filippucci et al., 2012 [5] who demonstrated tenosynovitis (except for extensor finger tendons that were not included in their study) in 44 (48.8%) of 90 RA patients and in 193 (8.3%) of 2340 tendons. The most frequently involved tendons were the ECU as well as the flexor tendons of the second, third, and fourth fingers. Their patients had median (range) age of 61.5 yr (23-83), mean DAS 28 of 4.19 ( ± 1.4), mean

HAQ of 1.34 (±0.8) and median (range) disease duration of 9 years (7-11). The preponderance of the ECU tenosynovitis is consistent with our finding and supported by other reports as a tendon frequently affected by inflammation and damage [19] . Moreover, in the prospective study done by Lillegraven et al., they found that the presence of ECU tensynovitis predicts the development of erosions [20] . The outcome of our study may therefore support the use of the ECU, being commonly involved tendon, as a reliable biomarker for damage. Our work revealed tendon damage in 6 (20%) of patients at the level of fingers and wrist. The main pathology was focal echotexture derangement. We found no evidence of tendon tears in our patients. The only involved tendons were the ECU, extensor tendon of fifth finger and flexor tendon of fourth finger. Only a few studies have looked at the ultrasound assessment of tendon damage in RA, observing a wide variability. Filippucci et al., 2012 [5] reported more tendon damage in their cohort, where they found tendon damage of 39 (43.3%) of 90 patients. They reported focal tendon echotexture derangement in 294 of 5400 (5.4%) tendons, partial tears in 14 (0.3%) and complete tears in 3 (0.06%). The tendon tears were only demonstrated at the level of wrist and the ECU was the most frequently involved tendon. The higher prevalence of tendon damage in the latter study may be due to the longer disease duration of their patients [median (range) disease duration of 9 years (7-11)] in comparison to our patients, based on the fact that in a longstanding disease the inflammation may lead to more tendon damage as in joints [21] .

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Hala I. Elgendy, et al.

Bruyn et al., [4] studied the posterior tibialis tendons at both ankles and the five medial extensor compartments at both wrists in 12 RA patients with median age (range) of 66.5 years (36-74), median disease duration (range) of 6.3 years (1-8.7) and median DAS 28; 3.79 (2.41-5.6). They revealed a partial rupture in 21% and a complete rupture in 2%. The ECU tendon was commonly involved. However in their study they graded the tendon damage only as partial and complete tear, and this lake of consensus on elementary lesions and definition of tendon damage may explain the discrepancy with our study and restricted the comparison. In general, the low prevalence of complete tendon rupture at the level of hands and wrists is probably due to the current treat-to-target strategy. In our study we evaluated the possible factors that may influence tendon involvement in our patients. We found that global disease activity and local joint synovitis were significantly related to finger and wrist tendons inflammation ( p-value 0.0217) and DAS 28 was the only variable associated with tendon inflammation. Our study has a few limitations. As, other comparable method for assessing the tendon lesion, such MRI was not done. However, a validity study showed comparative accuracy in diagnosing tendon damage between ultrasound and MRI [24] . With respect to tenosynovitis, Hoving et al., found US equivalent to MRI in the detection of tendon sheath disease at the hand and wrist in RA patients with early disease [25] . Conclusion and Recommendation: In conclusion, the present study provides a description of ultrasound detected tendon abnormalities in RA patients. Considering that the US can be time-consuming, the identification of the most commonly affected sites may facilitate US examination that can be focused on the target tendons in RA. The present study suggests that fourth and fifth finger tendons & extensor carpi ulnaris tendons should be included in US scorings for follow-up of RA patients. Also, in this study we tried to evaluate the relationship between tendon and joint involvement as well as other factors that are potentially associated with more frequent tendon involvement in RA patients. References 1- GENC HAKAN, CAKIT BURCU DUYUR, ERDEM HATICE RANA and TUNCBILEK ISIL: Ultrasonographic evaluation of tendons and enthesal sites in rheumatoid arthritis: Comparison with ankylosing spondylitis and healthy subjects. Clin. Rheumato., l24: 272-277, 2005.

Moreover they failed to identify a causal relationship between adjacent bone erosions and tendon rupture, as in many instances the erosions, although involving adjacent bones, were not directly under the path of the tendons in question [22] .

2- WAKEFIELD R.J., O’CONNOR P.J., CONAGHAN P.G., MCGONAGLED D., HENSOR E.A., et al.: Finger tendon disease in untreated early rheumatoid arthritis: A comparison of ultrasound and magnetic resonance imaging. Arthritis & Rheumatism, 57: 1158-1164, 2007.

Multivariate analysis of other factors that are potentially associated with more frequent tendon

3- BIANCHI S., MARTINOLI C. and ABDELWAHAB I.F.: Ultrasound of tendon tears Part 1: general considerations and upper extremity. Skeletal Radiol., 34: 500-12, 2005.

20 4- BRUYN GEORGE A.W., HANOVA PETRA, IAGNOCCO ANNAMARIA, D’AGOSTINO MARIA–ANTONIETTA, MÖLLER INGRID, et al.: Ultrasound definition of tendon damage in patients with rheumatoid arthritis, Results of the OMERACT consensus-based ultrasound score focusing on the diagnostic reliability. Ann. Rheum. Dis. doi: 10. 113 6/annrheumdis-2013 -203 596, 2013. 5- FILIPPUCCI EMILIO, GABBA ALESSANDRA, GESO LUCA DI, GIROLIMETTI RITA, SALAFFI FAUSTO and GRASSI WALTER: Hand tendon involvement in rheumatoid arthritis: An ultrasound study. Seminars in Arthritis and Rheumatism, 41: 752-760, 2012. 6- KIM HYUN AH, KIM SU HO and SEO YOUNG: Ultrasonographic findings of the shoulder in patients with rheumatoid arthritis and comparison with physical examination. J. Korean Med. Sci., 22: 660-6, 2007. 7- FILLIPUCCI E., IAGNOCCO A., MEENAGH G., DELLE A. SEDIE, RIENTE L., et al.: Ultrasound imaging for the rheumatologist II: Ultrasonography of the hand and wrist. Clin. Exp. Rheumatol., 24: 118-22, 2006. 8- ARNETT F.C., EDWORTHY S.M., BLOCH D.A., McSHANE D.J., FRIES J.F., et al.: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum., 31: 315, 1988. 9- ALETAHA DANIEL, NEOGI TUHINA, SILMAN ALAN J., FUNOVITS JULIA, FELSON DAVID T., et al.: Rheumatoid arthritis classification criteria. Arthritis & Rheumatism, 62: 2569-2581, 2010. 10- SCHUELLER-WEIDEKAMM CLAUDIA: Quantification of synovial and erosive changes in rheumatoid arthritis with Ultrasound. European Journal of Radiology, 71: 225231, 2009. 11- SOKKATUULIKKI: Radiographic scoring in rheumatoid arthritis, a Short introduction to the methods. Bulletin of the NYU Hospital for Joint Diseases, 66 (2): 166-8, 2008. 12- Van der HEIJDE D.: How to read radiographs according to the Sharp/van der Heijde method. J. Rheumatol., 27 (1): 261-3, 2000. 13- BACKHAUS M., BURMESTER G.R., GERBER T., GRASSI W., MACHOLD K.P., et al.: Guidelines for musculoskeletal ultrasound in rheumatology. Annals of the Rheumatic Diseases, 60: 641-649, 2001. 14- WAKEFIELD R.J., BALINT P.V., SZKUDLAREK M., FILIPPUCCI E., BACKHAUS M., et al.: OMERACT 7 special interest group; musculoskeletal ultrasound including definitions for ultrasonographic pathology. J. Rheumatol., 32 (12): 2485-7, 2005. 15- NAREDO E., COLLADO P., CRUZ A., PALOP M.J., CABERO F., et al.: Longitudinal power Doppler ultrasonographic assessment of joint inflammatory activity in early rheumatoid arthritis: Predictive value in disease

Ultrasonographic Evaluation of Hand & Wrist Tendons activity and radiologic progression. Arthritis Rheum., 57: 16-24, 2007. 16- NAREDO E., WAKEFIELD R.J., IAGNOCCO A., TERSLEV L., FILIPPUCCI E., et al.: The OMERACT ultrasound task force; summary of advances and priorities. J. Rheumatol., 38: 2063-7, 2011. 17- SZKUDLAREK M., COURT-PAYEN M., JACOBSEN S., KLARLUNDMETTE, KLAUSEN T., OSTERGAARD M., et al.: Inter observer agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. Arthritis Rheum., 48: 955-962, 2003. 18- BACKHAUS M., KAMRADT T., SANDROCK D., LORECK D., FRITZ J., et al.: Arthritis of the finger joints: A comprehensive approach comparing conventional radiography, scintigraphy, ultrasound, and contrastenhanced magnetic resonance imaging. Arthritis Rheum., 42: 1323-45, 1999. 19- MICUMIHAELA C., SERRA SARA, FODOR DANIELA, CRESPO MANUEL and NAREDO ESPERANZA: Interobserver reliability of ultrasound detection of tendon abnormalities at the wrist and ankle in patients with rheumatoid arthritis. Rheumatology, 50: 1120-1124, 2011. 20- LILLEGRAVEN S., BOYESEN P., HAMMER H.B., OSTERGAARD M., UHLIG T., et al.: Tenosynovitis of the extensor carpi ulnaris tendon predicts erosive progression in early rheumatoid arthritis. Ann. Rheum. Dis., 70: 2049-50, 2011. 21- SMOLEN JOSEF S., ALETAHA DANIEL and STEINER G.: Does damage cause inflammation? Revisiting the link between joint damage and inflammation. Ann. Rheum. Dis., 68: 159-62, 2009. 22- McQUEEN F., BECKLEY V., CRABBE J., ROBINSON E., YEOMAN S. and STEWART N.: Magnetic resonance imaging evidence of tendinopathy in early rheumatoid arthritis predicts tendon rupture at six years. Arthritis & Rheum., 52 (3): 744-51, 2005. 23- ALCALDE MARIA, D’AGOSTINO MARIA ANTONIETTA, BRUYN GEORGE A.W., MÖLLER, INGRID, IAGNOCCO ANNAMARIA, et al.: A systematic literature review of US definitions, scoring systems and validity according to the OMERACT filter for tendon lesion in RA and other inflammatory joint diseases. Rheumatology (Oxford), 51 (7): 1246-60, 2012. 24- SWEN W.A.A., JACOBS J.W.G. and HUBACH P.C.: Comparison of sonography and magnetic resonance imaging for the diagnosis of partial tears of finger extensor tendons in rheumatoid arthritis. Rheumatology, 39: 5562, 2000. 25- HOVING J.L., BUCHBINDER R., HALL S., LAWLER G., COOMBS P., et al.: A comparison of magnetic resonance imaging, sonography, and radiography of the hand in patients with early rheumatoid arthritis. J. Rheumatol., 31: 663-75, 2004.

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