The association between echogenicity and progression of Dupuytren's disease (DD): Birth of an imaging biomarker?

BACKGROUND: The shift of focus towards disease-controlling treatments to prevent DD progression at an early stage underlines the need for objective and reliable measurements that can monitor and predict the course of disease. Ultrasound has been studied as a potential tool for this purpose. This study examined to what extent echogenicity of early DD nodules predicts clinical progression. METHODS: Sonographic assessments of Dupuytren's nodules were performed by the same observer on 151 participants as part of an ongoing prospective cohort study on the course of DD. Echogenicity was assessed by determining the greyness of a nodule relative to the surrounding tissue, using ImageJ software. Progression of disease was defined as 1) an increase in total passive extension deficit (TPED) of ≥15 degrees and 2) surgical intervention of the examined ray, both occurring after the sonographic assessment. The associations between echogenicity and time to progression were estimated using Cox-regression models. RESULTS: The association between echogenicity and time to TPED progression showed that for every additional decrease of 1% in relative greyness (darker image) of a nodule, the risk of TPED progression during follow-up increases by 3.4% (hazard ratio [HR] = 0.966, 95% confidence interval [CI]: 0.935-0.966). Similarly, echogenicity was also associated with time to surgical intervention (HR = 0.967, 95% CI: 0.938-0.997), which indicates a higher risk for surgery during follow-up for darker nodules. CONCLUSIONS: These results suggest that echogenicity is predictive of the prognosis of the early stages of DD and might potentially be used as a prognostic imaging biomarker in the future.

Delayed vascular complication after collagenase injection for Dupuytren disease.

BACKGROUND: Vascular adverse events after collagenase injection for Dupuytren disease are absent in large trials and systematic reviews. The aim of this study is to present a case series of delayed vascular complications after collagenase treatment. METHODS: A prospective evaluation of 1181 consecutively treated patients at one orthopedic department identified three patients reporting symptoms of possible vascular complication. Baseline demographics and description of symptoms were collected, with a physical examination documenting extension deficit and neurovascular status. All patients completed the Cold Intolerance Symptom Severity (CISS) scale (range 4-100, lower is better) and underwent Doppler sonography examination of the digital arteries. RESULTS: All patients were treated in the small finger and two had an isolated proximal interphalangeal joint contracture. All patients had a delayed presentation of a few months, with episodes of white discoloration of the treated finger relieved within 30 min and associated with variable pain, paresthesia, stiffness and weakness. Two of the patients reported cold exposure as an episode trigger and had a pathological CISS score (40 and 36, respectively). Doppler sonography identified a nonpatent ulnar digital artery in one patient. CONCLUSIONS: Delayed vascular complication after collagenase treatment is rare, but surgeons and patients should be aware of the risk, especially when treating the small finger.

Tardigrade and Manifold Sign: Two New Signs in Dupuytren's Disease.

Dupuytren's disease (DD) is a chronic benign fibroproliferative disorder of the palmar and digital fasciae. It is characterized by formation of nodules and fibrous cords that may eventually lead to contractures with permanent flexion of the finger joints. Correction of the flexion contractures in advanced disease is still performed by open limited fasciectomy; ultrasonography (US)-guided minimally invasive treatment is preferred for early disease.We provide an overview of the detailed anatomy of the palmar aponeurosis and the structures that may be involved in DD. Although magnetic resonance imaging is used as the gold standard, these small anatomical structures are often better visible on US. We describe two new morphological signs due to thickening of these small structures in patients with DD: the tardigrade sign and the manifold sign. Familiarity with detailed imaging anatomy and these new imaging signs of DD will help confirm a correct and early diagnosis and distinguish this disease from various other entities.

Ultrasound-guided aponeurotomy and interphalangeal joint capsular release for treatment of Dupuytren's disease.

This study describes a new ultrasound-guided surgical technique for aponeurotomy and interphalangeal joint capsular release in patients with Dupuytren's disease and analyses the clinical outcomes. We carried out a retrospective review of 70 digits in 35 patients who underwent ultrasound-guided aponeurotomy and interphalangeal joint capsular release, with a minimum follow-up of 2 years. The primary outcome was the correction of the deformity and the QuickDASH questionnaire score after surgery and at 1 and 2 years. The secondary outcome was the presence of residual contracture immediately after surgery. The mean QuickDASH score fell from 28 before surgery to 14 after surgery. A significant decrease of -63° was observed for the global contracture, -35° the metacarpophalangeal joint contracture and -28° for the proximal interphalangeal joint contracture. Ultrasound-guided aponeurotomy and interphalangeal joint capsular and palmar plate releases are highly accurate and safe.Level of evidence: IV.

Echogenicity of Dupuytren's nodules is correlated to myofibroblast load and nodule hardness.

This study aimed to determine the association between the echogenicity of Dupuytren's disease nodules and myofibroblast load, and between echogenicity and nodule hardness. Thirty-eight nodules were assessed sonographically. The echogenicity of nodules was measured objectively with Image J (grey-value) and subjectively by visual inspection (hypo-, mixed and hyper-echogenicity). These findings were compared with myofibroblast load measured by histopathological analysis. In a different cohort, 97 nodules were assessed for grey-value and nodule hardness using a tonometer. There was a moderate, significant, negative association between grey-value and myofibroblast load and the subjective visual measurements corresponded to this finding. There was also a moderate, significant, negative association between grey-value and nodule hardness. Ultrasound and tonometry may be useful in the selection of patients for possible future preventive treatments.

Can collagenase effectiveness in Dupuytren's contracture be improved by using ultrasound-guided Injection? A comparative study.

The objective of this study was to compare the effectiveness of ultrasound-guided injection of collagenase Clostridium histolyticum (CCH) in patients with Dupuytren's contracture (DC), with the standard injection. We hypothesised that the ultrasound-guided Injection of CCH is more effective than the standard injection. A prospective cohorts study in patients with DC was done. We treated consecutively 47 fingers with the standard injection and 43 with the ultrasound-guided. Patients in both groups had the same inclusion criteria. The degrees of contracture of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were measured before treatment and after three months. We compared the effectiveness of each type of injection in respect to obtaining a complete finger extension and to the percentage of improvement in each finger and in each joint. With ultrasound-guided injection, complete finger extension was obtained in 54% of cases and an 81% mean percentage of correction of the finger contracture; with standard injection 49% and 77%, respectively. In the MCP joint, the mean percentage of correction was 92.5 % in the ultrasound-guided Injection group and 84% in the standard injection group. In the PIP joint, it was 75.1% in the ultrasound-guided injection group and 65.3% in the standard injection group. These results showed no statistical significance. Hand surgeons must balance the possible benefits of the ultrasound-guided injection with the complexity and resources needed to perform the technique.

Magnetic resonance imaging of diffusion characteristics following collagenase clostridium histolyticum injection in Dupuytren's contracture.

PurposeWe aimed to evaluate the extent of collagenase clostridium histolyticum (CCH) diffusion in Dupuytren's contracture (DC) for tissues outside of the contracture cord using Magnetic Resonance Imaging (MRI) immediately after CCH injection. Methods: 10 male patients aged 57-79 with DC of the metacarpophalangeal (MCP) joints were examined. Extension deficits were 10-60°(mean, 34.3) and 0-60°(mean, 26.6) in the MCP and proximal interphalangeal (PIP) joints, respectively. CCH injection was performed according to the standard method. MRI was performed within 15 min of CCH injection. Results: In all 10 cases, the extended area of high-intensity signal change outside of the cord was observed on short-T1 inversion recovery images (STIRs). Continuity from the insertion site was observed in the area of signal change involving the flexor tendon and neurovascular bundle. The signal change area spanned distally and proximally beyond the injection level. The signal change area expanded along the tendon sheath but no signal changes were observed inside the flexor tendon, suggesting the tendon sheath serves as a protective barrier from the CCH solution. After 1 week of injection, the mean decrease in contracture was 32.5°(94.7%) for the MCP joint and 19.8°(74.4%) for the PIP joint. In nine out of 10 cases, the extension deficit was within five degrees of full extension in the affected finger. There was no neurovascular injury or tendon rupture at 3 months of observation. Conclusions: MRI indicated the possible leakage of the drug outside of the cord during the early phase after administration, suggesting that CCH could persistently affect healthy tissues until CCH inactivates its enzyme process.

Preoperative ultrasonography and magnetic resonance imaging evaluation of the position of the neurovascular bundle for Dupuytren's disease of the fifth digit.

BACKGROUND: Dupuytren's contracture (DC) is a fibrosing disor-der that produces pathological subcutaneous nodules and cords in the normal fascia. The isolated occurrence of Dupuytren's disease of the fifth digit is uncommon. This study is aimed to describe the imaging features of an isolated digital cord of the small finger and its relationship with the neurovascular bundle. METHODS: A total of 13 hands in 13 patients who were clinically diagnosed with an isolated occurrence of Dupuytren's disease of the small finger were included between October 2008 and October 2013. Two independent radiologists used ultrasound and magnetic reso-nance imaging (MRI) to record size, signal or echogenicity, contrast enhancement or hyperemia, calcification, and anatomical features of the cord and its relationship with the neurovascular bundle. RESULTS: We found that ultrasound and MRI were accurate for the detection of the cords and neurovascular bundles in the small finger. The intermodality agreement between MRI and ultrasound was 100% for the detection of 6 spiraling bundles containing 13 isolated cords (46.2%). Among the subjects examined, 100% of the hands had ab-ductor digiti minimi (ADM) area involvement, and the distal insertion of the cord was on the ulnar side of the base of the middle phalanx. On MRI, all of the cords showed predominantly low signal intensity on both T1- and T2-weighted images. On ultrasound, the ulnar cord showed a hyperechoic or isoechoic appearance in 69.3% of hands and a hypoechoic appearance in 30.7% of hands. CONCLUSIONS: The spiraling of the bundle in the isolated occurrence of Dupuytren's disease at the small finger is a frequent occurrence. MRI and ultrasound are good imaging modalities for the evaluation of the relationship between the neurovascular bundle and the isolated cord.

Ultrasound as a complementary diagnostic method for Dupuytren's Contracture.

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Reliability and Interpretability of Sonographic Measurements of Palmar Dupuytren Nodules.

PURPOSE: In the future, it is expected that treatment of Dupuytren disease (DD) may shift toward control of early disease. Ultrasound might be an accurate method to measure the outcome of such treatment. The aim of this study was to assess the reliability of sonographic measurement of palmar nodules. METHODS: Fifty patients with nodules characteristic for early disease were assessed with ultrasound by 2 observers. Four different aspects of DD nodules were measured in the transversal and sagittal planes, width, depth, circumference, and area. The intra- and interobserver reliabilities were calculated using the intraclass correlation coefficient (ICC). The standard error of measurement (SEM) and the smallest detectable change (SDC) were also calculated for each aspect. RESULTS: The intraobserver reliability was good (ICC, 0.724 [0.562-0.833] to 0.886 [0.808-0.934]), except for width in the sagittal direction (ICC, 0.671 [0.484-0.799]). The interobserver reliability was moderate (ICC, 0.385 [0.126-0.596] to 0.757 [0.538-0.869]). The intraobserver ICCs of area were highest (transverse, 0.847 [0.744-0.893]; sagittal, 0.886 [0.808-0.934]). The SEM and SDC of area were 6.1 and 16.9 mm2 in the transverse and 8.0 and 22.2 mm2 in the sagittal plane. CONCLUSIONS: The intraobserver reliability of sonographic assessment of DD nodules is good. The measurement of area is the most reliable and is, therefore, recommended for future studies. However, even single-observer measurements have a clear dispersion, and a change beyond 16.9 (61%) and 22.2 mm2 (79%) has to be observed in the transverse and sagittal planes, respectively, before it can be considered as regression or progression. CLINICAL RELEVANCE: Repeated ultrasonographic measurements in DD should ideally be done by a single observer, using area of the nodule in the sagittal plane. Change beyond 16.9 (transverse) and 22.2 (sagittal) mm2 can be considered as a real change in nodule size.

OPTIMAL INJECTION DEPTH FOR COLLAGENASE CLOSTRIDIUM HISTOLYTICUM DETERMINED BY ULTRASONOGRAPHY IN THE TREATMENT OF DUPUYTREN´S DISEASE.

INTRODUCTION: A non-surgical procedure for the treatment of Dupuytrens disease is a palmar injection of Collagenase Clostridium Histolyticum to the recommended depth of “around 2-3 mm”. However, there is little supporting evidence from the literature to substantiate this. The aim of this study was to evaluate the “optimal depth” for injection of Collagenase Clostridium Histolyticum by ultrasonography for the treatment of Dupuytrens disease. MATERIAL AND METHODS: A total of 43 patients were enrolled in this study. We marked the collagenase injection point on the skin above the cord before injection. We then measured the distance from the surface of the skin to the middle of the cord by ultrasonography long axis imaging and defined this as the “optimal depth”. RESULTS: The average depth from the skin to the centre of the cord was 2.4 mm. The average distance from the surface of the skin to the proximal surface of the cord was 1.0 mm and the average thickness of the cord was 2.7 mm. CONCLUSION: By precise measurement of individual cases utilising ultrasonography we were able to confirm that the recommendations for injection depth as provided by the supplier of Collagenase Clostridium Histolyticum (2-3 mm) were in agreement with our findings. However no objective guide was supplied as with regards to interindividual variability between patients and we suggest that the use of preliminary ultrasonography will likely provide improved outcomes.

Imaging for Dupuytren disease: a systematic review of the literature.

BACKGROUND: As treatment of Dupuytren disease (DD) is expected to shift towards prevention of progression, the use of imaging in patients with DD becomes more important. In this systematic review an overview is given of the different methods for and applications of imaging for DD that have been described. METHODS: The MEDLINE and EMBASE databases were searched for articles reporting the use of imaging in patients with DD, published before May 17, 2018. Studies were systematically examined in two rounds by two observers according to the PRISMA systematic. All studies containing original data on imaging for DD were considered for inclusion. RESULTS: Three hundred and seven unique studies were identified, of which 23 were included in the study. Only studies on the use of ultrasound (US) and magnetic resonance imaging (MRI) were identified. Broadly, articles could be divided into 5 categories. Seven studies were found on diagnosis, two on measurement of disease extent, four on measurement of disease activity, seven on guidance of minimally invasive procedures and five studies on evaluation of treatment. According to the Oxford CEBM, the levels of evidence were low, ranging from level 3 to 5. CONCLUSIONS: A variety of applications for US and MRI for patients with DD has been described. Based on the results of this review, the largest value for imaging lies in the measurement of disease activity and the follow-up of treatment of patients with early stage disease. Unfortunately, the overall level of evidence of the available literature was low. Future research is necessary to define the exact value of US and MRI in the management of patients with DD.

Ultrasound Features of Palmar Fibromatosis or Dupuytren Contracture.

OBJECTIVES: To retrospectively characterize the ultrasound appearance of palmar fibromatosis in patients with a surgical or clinical diagnosis of palmar fibromatosis. METHODS: A search of ultrasound reports from 2005 to 2015 and a subsequent search of medical records were performed to identify patients with a surgical or clinical diagnosis of palmar fibromatosis. The ultrasound images were retrospectively reviewed to record the lesion location, size, echogenicity, compressibility, hyperemia, and calcification. RESULTS: A total of 36 patients were identified (average age, 60 years; 61% male), yielding a total of 55 palmar fibromatosis lesions, of which 2%, 7%, 29%, 36%, 20%, and 5% were located at the first, second, third, fourth, and fifth digits and between the fourth and fifth digits, respectively. The lesions were located directly superficial to the flexor tendons in 93% with their epicenters at the distal metacarpal in 89%. Average lesion dimensions were 13.1 mm in length, 6.8 mm in width, and 2.5 mm in depth. On ultrasound images, the lesions were characteristically hypoechoic (98%) and noncompressible (95%). Atypical features included calcification (2%), compressibility (5%), hyperemia on color Doppler images (6%), epicenters at the metacarpophalangeal joint (7%) or proximal phalanx (4%), and location superficial but lateral to the flexor tendons (7%). CONCLUSIONS: Palmar fibromatosis most commonly appears hypoechoic and is located directly superficial to the flexor tendons with an epicenter at the distal metacarpal, most commonly the fourth digit. However, the epicenter location may be at the distal metacarpal and proximal phalanx of other digits, adjacent to the flexor tendons, with possible hyperemia and calcification.

High-energy focused extracorporeal shockwave therapy relieved pain in Dupuytren's disease: a series of seven hands.

BACKGROUND: Dupuytren's disease of the hand is characterized by progressive thickening and shortening of palmar fascia resulting in flexion deformities of the digits and hence limitation of hand function. The objective of this study was to evaluate the effectiveness of shock-wave therapy on patients with Dupuytren's disease of the hand. CASE REPORT: A case series study observed a total of four patients with Dupuytren's disease of the hand. All 4 patients had diabetes. Three patients had bilateral hand involvement. Two patients had flexion deformity. High-energy focused extracorporeal shockwave therapy was applied using a Storz Duolith SD1 (2000 impulses, 3 Hz, 1.24 mJ/mm2) in 5 sessions with 7 days between. Outcome measured included pain score, tender score, hand grip, and nodule size from the Michigan Hand Outcome Questionnaire, JAMAR hand held dynamometer, and ultrasonography. Data was collected at the entry and conclusion of the study at 0 and 8 weeks. CLINICAL REHABILITATION IMPACT: Significant statistical improvement was observed for pain score 8.7±0.5 vs. 2.0±0.9, P<0.001 and for tender score 8.5±0.5 vs. 2.5±0.9, P<0.009 after the therapy. Decrease in size of nodules with improvement of flexion deformity was observed in one patient who had multiple bilateral nodules. No adverse effects were noted. Extracorporeal shockwave therapy was beneficial in relieving symptoms in Dupuytren's disease of the hand.

Morphological patterns of the pretendinous cord in Dupuytren's disease: a predictor of clinical outcome?

The morphology of the pretendinous cord in Dupuytren's disease is poorly described in vivo and especially with respect to recurrence after treatment. This prospective study was designed to describe the morphology of Dupuytren's cords by ultrasound and to identify possible correlation between the ultrasonographic characteristics of these cords and the clinical outcomes two years after treatment. Thirty-nine patients with a contracture of at least 20° in the metacarpophalangeal (MCP) joint, who were scheduled for local treatment by either injectable collagenase clostridium histolyticum (CCH) or percutaneous needle fasciotomy (PNF), were examined by ultrasound. The echogenicity and position of the pretendinous cords in relation to flexor tendons and neurovascular bundles were categorized. The structure of the cords was described and characterized as predominantly nodular or fibrillar. All 39 patients were assessed clinically after two years. A majority of the patients (84%) had cords with nodular components, and six patients (16%) had fibrillar cords. After two years, the clinical results were compared to the ultrasonographic findings before treatment. Three patients had recurrent contracture, and a retrospective analysis showed that all of these patients had cords with mixed echogenicity and nodules before treatment. Fifteen patients had a palpable pretendinous cord, and all but one of these had cords with mixed echogenicity and nodular structure before treatment. This pilot study indicates that some ultrasonographic features of the Dupuytren's cord, such as mixed echogenicity and nodular structure, may predict recurrence after minimally invasive treatment for Dupuytren's contracture. However, a larger study in correlation with histological examination of the excised cords would be necessary to confirm the pathoanatomical significance of these ultrasonographic features.

T2 signal intensity as an imaging biomarker for patients with superficial Fibromatoses of the hands (Dupuytren's disease) and feet (Ledderhose disease) undergoing definitive electron beam irradiation.

OBJECTIVE: Electron beam therapy is a definitive radiation treatment option for superficial fibromatoses of the hands and feet. Because objective criteria for treatment response remain poorly defined, we sought to describe changes in electron beam treated lesions on MRI. MATERIALS AND METHODS: The study included 1 male and 9 female patients with a total of 37 superficial fibromatoses; average age was 60.7 years. Standard 6 MeV electron beam treatment included 3 Gy per fraction for 10 or 12 treatments using split-course with 3-month halfway break. Pre- and post-treatment MRIs were evaluated to determine lesion size (cm3), T2 signal intensity and contrast enhancement (5-point ordinal scales) by a fellowship trained musculoskeletal radiologist. MRI findings were correlated with clinical response using a composite 1-5 ordinal scale, Karnofsky Performance Scale and patient-reported 10-point visual analog scale for pain. RESULTS: Mean volume decreased from 1.5 to 1.2 cm3 (p = 0.01, paired t-test). Mean T2 hyperintensity score decreased from 3.0 to 2.1 (p < 0.0001, Wilcoxon signed-rank). Mean enhancement score available for 22 lesions decreased from 3.8 to 3.0 (p < 0.0001, Wilcoxon signed-rank). Performance scores improved from 78.9 ± 13.7 to 84.6 ± 6.9 (p = 0.007, paired t-test). Pain scores decreased from 3.0 ± 3.3 to 1.1 ± 2.0 (p = 0.0001, paired t-test). Post-treatment T2 signal correlated weakly with performance and pain (Spearman's ρ = -0.37 and 0.16, respectively). CONCLUSIONS: MRI is valuable for evaluating patients undergoing electron beam therapy for superficial fibromatoses: higher pretreatment T2 intensity may predict benefit from radiotherapy. T2 hypointensity may be a better marker than size for therapeutic effect.

Ultrasonographic examination of the ruptured cord after collagenase treatment or needle fasciotomy for Dupuytren's contracture.

Local treatment of Dupuytren's contracture, either by collagenase or needle fasciotomy, allows disruption of the pathological cord during forced extension. The purpose of this study was to investigate the cord before and after both treatments by ultrasound. A total of 39 patients with a minimum of 20° contracture in the metacarpophalangeal joint were included and randomized to treatment with either collagenase (20 patients) or needle fasciotomy (19 patients). The distance between the distal and the proximal parts of the ruptured cord was measured by ultrasound and the difference in passive joint movement before and after treatment was measured with a goniomenter. There were no significant differences between the collagenase and needle fasciotomy groups in the size of the rupture or gain of mobility. Most cords treated with collagenase and subsequent forced extension had the same ultrasonographic appearance as cords disrupted mechanically by needle fasciotomy. LEVEL OF EVIDENCE: III.

Long-term follow-up of Dupuytren disease after injection of triamcinolone acetonide in Chinese patients in Taiwan.

Injection of triamcinolone acetonide is a non-operative treatment for early-stage Dupuytren disease in Caucasians, but its effectiveness in non-Caucasians is unclear. We report averaged 5-year follow-up results of 37 patients (49 affected hands) with early-stage Dupuytren disease for patients in Taiwan (non-Caucasian) who received a single dose of 5 mg triamcinolone acetonide injection into nodules monthly for 3 months. Using ultrasound, we recorded no progression of sizes of the modules following injection after 6 months. After an average 5-year follow-up, two patients with three hands (6%) experienced reactivation of the treated nodules. None required surgical intervention. Ultrasound examination showed that sizes of the treated Dupuytren nodules decreased significantly by 40% 6 months after injection and 56% at the final follow-up. We conclude that in these Chinese patients in Taiwan with early Dupuytren nodules, triamcinolone acetonide injection was effective in reducing the size of the Dupuytren nodules and maintaining long-term durable control of the nodular growth. LEVEL OF EVIDENCE: III.

Patient Satisfaction With Collagenase.

PURPOSE: To establish patient satisfaction after collagenase clostridium histolyticum (CCH) injection. METHODS: In a cross-sectional study, 213 patients who had been treated for Dupuytren disease with CCH were reviewed between 37 and 1421 days after injection. RESULTS: A total of 73% of the patients were very satisfied or satisfied, and 21% were dissatisfied; 75% would probably or definitely have CCH again, whereas 17% probably or definitely would not. We found that satisfaction and willingness to undergo a second treatment decreased over time and had a negative relationship with recurrence. Dissatisfaction was greater in those with a poor initial outcome but not in those with an initial complication. Of 212 patients, 78 had previously experienced surgery for Dupuytren disease of whom 71% would prefer CCH to surgery and 15% the converse. Satisfaction shows a relationship with function as measured by both QuickDASH and the Southampton Dupuytren Scoring Scheme. CONCLUSIONS: Patient satisfaction with CCH is generally high but deteriorates over time as the disease recurs. To manage patient expectation, this issue should be made explicit to patients in the consent process. CLINICAL RELEVANCE: Overall satisfaction with CCH is high, with initial satisfaction rates especially good. Forewarning of complications and recurrence can help maintain satisfaction levels.