Search

Background The focus of research and management of Dupuytren’s disease (DD) is shifting from relieving symptoms in the later stages of disease towards the prevention of contractures. Treatment services might likewise shift towards primary care. Studying characteristics of DD patients who seek medical care for the first time, may identify a symptomatic target group for early DD treatments. We present the first study that estimates the incidence and prevalence of DD in primary care by applying a text-mining algorithm to registration data.Methods This is a population-based cohort study using electronic health records from Dutch general practices involved in a regional research network. Descriptive statistics were used to describe sex, age, comorbidities and lifestyle factors, the latter two were identified via International Classification of Primary Care (ICPC) codes. Incidence rate was calculated as number of patients with a first contact for DD/1000 person years for the years 2017–2021, point prevalence as the percentage of patients with a contact for DD in 2021. DD contacts were identified using a text-mining algorithm.Results The incidence ranged between 1.41 and 1.72/1000 person years and the overall prevalence was 1.99%. Incidence and prevalence are higher among males and increase with age, peaking between 61 and 80 years.Conclusions Our results of prevalence and incidence of DD in primary care give an insight into the relevant population of patients with symptomatic DD that might be the future target group for potential disease controlling treatments.

Abstract Dupuytren’s disease (DD) is a highly heritable fibrotic disorder of the hand with incompletely understood etiology. A number of genetic loci, including Wnt signaling members, have been previously identified. Our overall aim was to identify novel genetic loci, to prioritize genes within the loci for functional studies, and to assess genetic correlation with associated disorders. We performed a meta-analysis of six DD genome-wide association studies from three European countries and extensive bioinformatic follow-up analyses. Leveraging 11,320 cases and 47,023 controls, we identified 85 genome-wide significant single nucleotide polymorphisms in 56 loci, of which 11 were novel, explaining 13.3–38.1% of disease variance. Gene prioritization implicated the Hedgehog and Notch signaling pathways. We also identified a significant genetic correlation with frozen shoulder. The pathways identified highlight the potential for new therapeutic targets and provide a basis for additional mechanistic studies for a common disorder that can severely impact hand function.

Abstract Dupuytren’s disease is a chronic, progressive fibroproliferative condition of the hand fascia which results in digital contraction. So far, treatments do not directly interfere with the (myo)fibroblasts that are responsible for the formation of the collagen-rich cords and its contraction. Here we investigated whether verteporfin (VP) is able to inhibit the activation and subsequent differentiation of DD nodular fibroblasts into myofibroblasts. Fibroblasts were isolated from nodules of 7 Dupuytren patients. Cells are treated (1) for 48 h with 5 ng/ml transforming growth factor β1 (TGF-β1) followed by 48 h with/without 250 nM VP in the absence of TGF-β1, or treated (2) for 48 h with TGF-β1 followed by 48 h with/without VP in the presence of TGF-β1. mRNA levels were measured by means of Real-Time PCR, and proteins were visualized by means of Western blotting and/or immunofluorescence. Quantitative data were statistically analyzed with GraphPad Prism using the paired t-test. We found that fibroblasts activated for 48 h with TGF-β1 show a decrease in mRNA levels of COL1A1, COL3A1, COL4A1, PLOD2, FN1EDA, CCN2 and SERPINE1 when exposed for another 48 h with VP, whereas no decrease is seen for ACTA2, YAP1, SMAD2 and SMAD3 mRNA levels. Cells exposed for an additional 48 h with TGF-β1, but now in the presence of VP, are not further activated anymore, whereas in the absence of VP the cells continue to differentiate into myofibroblasts. Collagen type I, fibronectin-extra domain A, α-smooth muscle actin, YAP1, Smad2 and Smad3 protein levels were attenuated by both VP treatments. We conclude that VP has strong anti-fibrotic properties: it is able to halt the differentiation of fibroblasts into myofibroblasts, and is also able to reverse the activation status of fibroblasts. The decreased protein levels of YAP1, Smad2 and Smad3 in the presence of VP explain in part the strong anti-fibrotic properties of VP. Verteporfin is clinically used as a photosensitizer for photodynamic therapy to eliminate abnormal blood vessels in the eye to attenuate macular degeneration. The antifibrotic properties of VP do not rely on photo-activation, as we used the molecule in its non-photoinduced state.

Abstract Purpose Patient-reported outcome measures are essential in the evaluation of facial palsy. Aim of this study was to translate and validate the Facial Disability Index (FDI) for use in the Netherlands. Methods The FDI was translated into Dutch according to a forward-backward method. Construct validity was assessed by formulating 22 hypotheses regarding associations of FDI scores with the Facial Clinimetric Evaluation scale, the Synkinesis Assessment Questionnaire, the Short Form-12 and the Sunnybrook Facial Grading System. Validity was considered adequate if at least 75% (i.e. 17 out of 22) of the hypotheses were confirmed. Additionally, confirmatory factor analysis was performed. Cronbach’s α was calculated as a measure of internal consistency. Participants were asked to fill out the FDI a second time after 2 weeks to analyse test-retest reliability. Lastly, smallest detectable change was calculated. Results In total, 19 hypotheses (86.4%) were confirmed. Confirmatory factor analysis showed acceptable fit for the two factor structure of the original FDI (root mean square error of approximation = 0.064, standardized root mean square residual = 0.081, comparative fit index = 0.925, Chi-square = 50.22 with 34 degrees of freedom). Internal consistency for the FDI physical function scale was good (α > 0.720). Internal consistency for the FDI social/well-being scale was slightly less (α > 0.574). Test-retest reliability for both scales was good (intraclass correlation coefficients > 0.786). Smallest detectable change at the level of the individual was 17.6 points for the physical function and 17.7 points for the social/well-being function, and at group level 1.9 points for both scales. Conclusion The Dutch version FDI shows good psychometric properties. The relatively large values for individual smallest detectable change may limit clinical use. The translation and widespread use of the FDI in multiple languages can help to compare treatment results internationally.

Abstract 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.

Background: Paralytic ectropion patients suffer from impairment of function and appearance of the lower eyelid and are at high risk of developing an exposure keratitis. A canthoplasty procedure can reduce the horizontal eyelid laxity and elevate the lower eyelid. We used a periosteal flap from the outer orbit to create a new canthal ligament. This study investigates the long-term outcomes of this technique. Methods: Cross-sectional outcome study in which 30 cases of paralytic ectropion are treated with a lateral periosteal flap canthoplasty after adequate eyelid shortening. At the desired canthal height, a periosteal flap from the outer temporal orbital rim is mobilized around the rim and sutured in a double-breasted fashion to a tarsal strip. Effect of the operation is measured by comparing preoperative and postoperative photographs for signs of ectropion. For this purpose, a new photograph-based scoring method [the Ectropion Severity Score (ESS)] was developed and evaluated. Results: The ESS proved to be reliable and sensitive to the presence of ectropion. Significant improvement of the ectropion sequelae was measured after a mean follow-up period of 2 years. In 3 cases (13%), a revision procedure was necessary because of relapse of lower eyelid sagging after a mean time of 1.9 years. In these cases, the periosteal flap could be reused. Conclusions: The ESS is a useful instrument to score the severity of paralytic ectropion. The periosteal flap canthoplasty is an effective procedure, with durable results in paralytic ectropion patients. The same periosteal flap can be used in a revision procedure.