Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals.

Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the second and third most strongly associated ones (P = 6.4 × 10-132 and P = 9.2 × 10-69, respectively). For the most strongly associated Neandertal variant, we identify EPDR1 as the causal gene. Dupuytren's disease is an example of how admixture with Neandertals has shaped regional differences in disease prevalence.

Biochemical and Histological Differences between Longitudinal and Vertical Fibres of Dupuytren's Palmar Aponeurosis and Innovative Clinical Implications.

Dupuytren's disease, a chronic and progressive fibroproliferative lesion of the hand, which affects the palmar fascia, has a recurrence rate after selective aponeurotomy of 20-40% at 5 years. This study focused, for the first time, on the microanatomical and histopathological characteristics of the longitudinal and vertical fibres (usually spared during surgery) in the aponeurosis with Dupuytren's disease, in different stages of the Tubiana's classification. Twelve human samples were collected and analysed by immunostaining, Total Collagen Assay, ELISA Immunoassay, and immunoblotting for the Von Willebrand factor, α-Sma, D2-40, CD-68, Total Collagen, Collagen-I and III, IL1ß, TNF-α to analyse the blood and lymphatic vascularization, the amount and distribution of collagen, and the inflammation. The results show a progressive increase in the arterial vascularization in the vertical fibres (from 8.8/mm2 in the early stage to 21.4/mm2 in stage 3/4), and a parallel progressive decrease in the lymphatic drainage (from 6.2/mm2 to 2.8/mm2), correlated with a local inflammatory context (increase in IL-1ß and TNF-α until the stage 2) in both the longitudinal and vertical fibres. The acute inflammation after stage 2 decreased, in favour of a fibrotic action, with the clear synthesis of new collagen (up to ~83 µg/mg), especially Collagen-I. These results clearly demonstrate the involvement of the septa of Legueu and Juvara in the disease pathology and the modifications with the disease's progression. A greater understanding of the pathology becomes fundamental for staging and the adequate therapeutic timing, to obtain the best morpho-functional result and the lowest risk of complications.

Collagenase clostridium histolyticum injection versus limited fasciectomy for the treatment of Dupuytren's disease: a systematic review and meta-analysis of comparative studies.

INTRODUCTION: The aim of the present study is to systematically review the literature on well-selected comparative studies for meta-analysis on outcome differences between collagenase clostridium histolyticum (CCH) injection and limited fasciectomy (LF) for Dupuytren's disease. MATERIALS AND METHODS: PubMed/Medline, Embase, and the Cochrane Library were searched for comparative studies assessing differences in outcomes of CCH and LF. Effect estimates were pooled across studies using random effects models and presented as weighted mean difference (MD) and odds ratio (OR) with corresponding 95% confidence interval (CI). RESULTS: A total of 11 studies encompassing 1'051 patients was included (619 patients in the CCH and 432 in the LF group). The residual contracture at a minimal average follow-up of three months was higher in the CCH group than in the LF group (27.8 vs. 16.2°, MD 11.6°, 95% CI [8.7, 14.5°], p < 0.001). The recurrence rate was significantly higher in the CCH group (25.8 vs. 9.3%, OR 5.2, 95% CI [1.5, 18.8], p = 0.01) while the rate of severe complications was significantly higher in the LF group (0.3 vs. 7.3%, OR 0.12, 95% CI [0.03, 0.42], p = 0.001). CONCLUSIONS: Evidence of the present study confirms that CCH injection has a higher rate of disease recurrence whereas LF carries a higher risk for severe complications. It's imperative that the trade-off between these aspects is considered, keeping in mind that CCH injections may be repeated in case of disease recurrence without increasing procedure related risks, especially in complex cases.

Soleful solutions: Advancements in treatment strategies for ledderhose disease.

INTRODUCTION: Ledderhose disease (plantar fibromatosis) is a benign and progressive proliferative disorder of the plantar fascia that forms fixed and painful nodules within the fascia, causing functional disability and decreased quality of life. METHODS: we conducted a narrative review using Pubmed (https://pubmed.ncbi.nlm.nih.gov/) and searched for the terms "Ledderhose disease" "plantar fibromatosis" "Ledderhose disease treatment" "plantar fibromatosis treatment" with further focused searches in Pubmed to supplement information regarding each intervention. RESULTS: many non-surgical therapeutic strategies are used in managing symptoms. These include pharmacological and non-pharmacological treatment options. Surgical treatment is employed when these therapies are not able to control the symptoms. CONCLUSION: understanding and exploring effective treatment modalities for Ledderhose disease (LD) is important in improving the functional disability and quality of life. This review aims to showcase a general outline of the condition and illustrate the present treatments used to manage the disease. LEVELS OF EVIDENCE: Therapeutic study, Level V.

Patients With Dupuytren Disease Use Excessive Grip Force When Lifting and Holding Small Objects, Independent of the Degree of Contracture.

OBJECTIVE: To identify the extent and quality of fine motor skill alteration in patients with Dupuytren disease (DD) using an instrumented device measuring grip forces, beyond the commonly used measurement of contracture. DESIGN: Case-control study. SETTING: University outpatient clinic. PARTICIPANTS: Patients with DD (N=27) and a contracture >45° (Tubiana stage II, III, and IV) were included and compared with age-matched healthy control patients (N=27). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES(S): All individuals were subjected to a set of specific tests using a new instrumented device ("manipulandum"). These included lifting, grasping, and then holding the "manipulandum" with 4 different object characteristics (light and heavy weight, rough and smooth surface) along with a measurement of the precision grip strength. Standard measurements including the Nine-Hole Peg Test, a two-point discrimination, and the Disability of Arm, Shoulder and Hand score were evaluated in comparison. RESULTS: Although the measurements of precision grip, two-point discrimination, Nine-Hole Peg Test, and Disability of Arm, Shoulder and Hand score showed no statistically significant differences between both groups, patients with DD applied significantly greater forces when tested with the different subtests using the "manipulandum." Analysis of the 2-phase movement (lifting and holding the "manipulandum") revealed highly significant differences between the groups. CONCLUSIONS: Patients with DD use excessive grip forces when lifting and holding the "manipulandum" when compared with healthy control patients, independent of the degree of contracture. As no differences in precision grip strength were seen, the presented approach is useful to obtain additional important information about fine motor function in diseased hands.

Assessing the Effect of Time from Injection of Collagenase to Manipulation on Success Rates in Dupuytren Disease.

PURPOSE: Dupuytren disease can be managed with an injection of collagenase Clostridium histolyticum enzyme followed by manual manipulation. Although the recommended time from injection to manipulation is 24-72 hours, patient and physician schedules may not accommodate this time frame. Therefore, we sought to study the impact of time from injection to manipulation on outcomes and complications of collagenase injection. METHODS: We performed a review of 309 patients who underwent an injection of collagenase Clostridium histolyticum for Dupuytren disease with manipulation at two, five, or seven days after injection. We compared preinjection and postinjection contracture angles as well as frequency of skin tears and tendon ruptures. RESULTS: Of the 309 patients, 207 underwent manipulation at two days, 32 at five days, and 70 at seven days. Patients had similar preinjection contracture angles. All patients demonstrated improvement in contracture after manipulation. Rates of skin tears and tendon ruptures were similar in all three groups. Significant predictors of complications included number of cords injected and history of previous collagenase injection, but not history of previous Dupuytren diagnosis. CONCLUSIONS: Although collagenase injection for Dupuytren disease is typically performed with plans for manipulation at 24-72 hours, postinjection manipulation could be performed as late as seven days without adversely affecting the frequency of skin and tendon complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Patient Insight With Collagenase Treatment for Dupuytren: A Prospective Study.

PURPOSE: There appears to be controversy regarding differing patient and physician perceptions of adverse effects (AEs) in the treatment of Dupuytren disease with collagenase clostridium histolyticum (CCH). The aim of this study was to compare the number, type, and severity of AEs perceived and reported by patients and by their physician METHODS: To assess AEs following CCH injection in a standardized way, patients were given a list of predefined complications and asked to rate their severity on a 4-point Likert scale ranging from 1 (serious) to 4 (insignificant). RESULTS: Eighty-five patients were included. Patients reported fewer AEs than their physician (mean, 1.48 vs 2.18). There was no agreement between physician- and patient-reported AEs except for skin lacerations, which showed fair agreement (κ = 0.257). CONCLUSIONS: Patients and physicians differ in their evaluation of AEs due to CCH treatment in Dupuytren disease. A fair level of agreement was observed for skin lacerations. CLINICAL RELEVANCE: Greater consensus is needed when defining AEs associated with CCH in the treatment of Dupuytren disease.

Targeting Myofibroblasts as a Treatment Modality for Dupuytren Disease.

PURPOSE: Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into adipocytes in vitro and alters their contractile nature in vivo. METHODS: Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry. RESULTS: Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treatments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not. CONCLUSIONS: Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion. CLINICAL RELEVANCE: The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture.

A shared genetic architecture between adhesive capsulitis and Dupuytren disease.

BACKGROUND: The etiology of adhesive capsulitis involves inflammation, thickening, and fibrosis of the shoulder capsule. The underlying genetic factors are poorly understood. The purpose of this study was to identify genetic variants associated with adhesive capsulitis using the UK Biobank (UKB) cohort and compare them with variants associated with Dupuytren disease investigating a common etiology between the 2 fibrotic disorders. METHODS: A genome-wide association study (GWAS) was performed using data from UKB with 10,773 cases of adhesive capsulitis, and a second GWAS was performed with 8891 cases of Dupuytren disease. Next, a comparison of association statistics was performed between adhesive capsulitis and Dupuytren disease using the data from both GWAS. Finally, single-nucleotide polymorphisms (SNPs) previously reported from candidate gene studies for adhesive capsulitis and Dupuytren disease were tested for association with adhesive capsulitis and Dupuytren disease using the summary statistics from their respective GWAS. RESULTS: The UKB GWAS for adhesive capsulitis identified 6 loci that reached genome-wide statistical significance: a cluster of 11 closely linked SNPs on chromosome 1; a single SNP on chromosome 2; a single SNP on chromosome 14; 2 closely linked SNPs on chromosome 21; 33 closely linked SNPs on chromosome 22; and 3 closely linked SNPs on the X chromosome. These SNPs were associated with 8 different genes including TSPAN2/NGF, SATB2, MRPL52/MMP14, ERG, WNT7B, and FGF13. A GWAS for Dupuytren disease was performed and a comparison to the adhesive capsulitis GWAS showed 13 loci significantly associated with both phenotypes. A validation attempt of 6 previously reported SNPs associated with adhesive capsulitis using UKB summary statistics was unable to confirm any of the previously reported SNPs (all P > .19). All 23 previously reported SNPs associated with Dupuytren disease were confirmed using the UKB summary statistics (P < 2.1 × 10-3) CONCLUSION: This GWAS investigating adhesive capsulitis has identified 6 novel loci involving 8 different genes to be associated with adhesive capsulitis. A GWAS investigating Dupuytren disease was performed and compared to the adhesive capsulitis GWAS, and 13 common loci were identified between the 2 disorders with genes involved in pathologic fibrosis. We were unable to validate the SNPs in candidate genes previously reported to be associated with adhesive capsulitis although we were able to confirm all previously reported SNPs associated with Dupuytren disease. The strong genetic overlap between the adhesive capsulitis and Dupuytren disease loci suggests a similar etiology between the 2 diseases.

Comparison of Rheological Properties of Healthy versus Dupuytren Fibroblasts When Treated with a Cell Contraction Inhibitor by Atomic Force Microscope.

Mechanical properties of healthy and Dupuytren fibroblasts were investigated by atomic force microscopy (AFM). In addition to standard force curves, rheological properties were assessed using an oscillatory testing methodology, in which the frequency was swept from 1 Hz to 1 kHz, and data were analyzed using the structural damping model. Dupuytren fibroblasts showed larger apparent Young's modulus values than healthy ones, which is in agreement with previous results. Moreover, cell mechanics were compared before and after ML-7 treatment, which is a myosin light chain kinase inhibitor (MLCK) that reduces myosin activity and hence cell contraction. We employed two different concentrations of ML-7 inhibitor and could observe distinct cell reactions. At 1 µM, healthy and scar fibroblasts did not show measurable changes in stiffness, but Dupuytren fibroblasts displayed a softening and recovery after some time. When increasing ML-7 concentration (3 µM), the majority of cells reacted, Dupuytren fibroblasts were the most susceptible, not being able to recover from the drug and dying. These results suggested that ML-7 is a potent inhibitor for MLCK and that myosin II is essential for cytoskeleton stabilization and cell survival.

Dupuytren's Disease Is Mediated by Insufficient TGF-ß1 Release and Degradation.

Dupuytren's disease (DD) is a fibroproliferative disorder affecting the palmar fascia, causing functional restrictions of the hand and thereby limiting patients' daily lives. The disturbed and excessive myofibroblastogenesis, causing DD, is mainly induced by transforming growth factor (TGF)-ß1. But, the extent to which impaired TGF-ß1 release or TGF-ß signal degradation is involved in pathologically altered myofibroblastogenesis in DD has been barely examined. Therefore, the complex in which TGF-ß1 is secreted in the extracellular matrix to elicit its biological activity, and proteins such as plasmin, integrins, and matrix metalloproteinases (MMPs), which are involved in the TGF-ß1 activation, were herein analyzed in DD-fibroblasts (DD-FBs). Additionally, TGF-ß signal degradation via caveolin-1 was examined with 5-fluoruracil (5-FU) in detail. Gene expression analysis was performed via Western blot, PCR, and immunofluorescence analyses. As a surrogate parameter for disturbed myofibroblastogenesis, 𝛼-smooth-muscle-actin (𝛼-SMA) expression was evaluated. It was demonstrated that latency-associated peptide (LAP)-TGF-ß and latent TGF-ß-binding protein (LTBP)-1 involved in TGF-ß-complex building were significantly upregulated in DD. Plasmin a serinprotease responsible for the TGF-ß release was significantly downregulated. The application of exogenous plasmin was able to inhibit disturbed myofibroblastogenesis, as measured via 𝛼-SMA expression. Furthermore, a reduced TGF-ß1 degradation was also involved in the pathological phenotype of DD, because caveolin-1 expression was significantly downregulated, and if rescued, myofibroblastogenesis was also inhibited. Therefore, our study demonstrates that a deficient release and degradation of TGF-ß1 are important players in the pathological phenotype of DD and should be addressed in future research studies to improve DD therapy or other related fibrotic conditions.

QuickDASH questionnaire items behave as 2 distinct subscales rather than one scale in Dupuytren's disease.

STUDY DESIGN: Retrospective cohort BACKGROUND: Exploratory Factor Analysis (EFA) and structural equation modelling (SEM) assess relationships between questionnaire items and the constructs ("factors") measured by a questionnaire. The QuickDASH has not been subjected to these analyses in Dupuytren's disease. PURPOSE: To undertake EFA and SEM to identify the factors measured by the QuickDASH in patients with Dupuytren's disease. METHODS: We identified 750 cases of surgery for Dupuytren's disease at a single center with preoperative QuickDASH scores. We performed EFA on QuickDASH responses in R, using established methodology. Based on the EFA results, we conducted SEM in a training sample of 200 participants. A test SEM analysis was performed in a second, independent sample of 200 participants. RESULTS: EFA suggested a 2-factor model. Items 1-6 measured one factor (we interpreted this as "hand function"), whereas items 9-11 measured a different factor ("hand symptoms"). Items 7 and 8 (social and work activities) did not reflect either of these factors well, and may be influenced by other variables. A structural equation model based on the EFA results, with 2 first-order factors, demonstrated excellent fit in our first SEM sample. This was confirmed with a second independent sample in a test analysis. CONCLUSIONS: The QuickDASH PROM may measure 2 distinct factors in patients with Dupuytren's disease. This aligns with previous analyses of the full-length DASH PROM. Separation of the QuickDASH PROM into 2 sub-scales with distinct scores to measure "hand function" and "hand symptoms" may improve its structural validity in patients with Dupuytren's disease.

Sorafenib in Dupuytren and Ledderhose Disease.

Palmar and plantar fibromatosis are benign proliferative processes which present as a diffuse thickening or nodules of the hands and/or feet and may lead to flexion contractures, pain, and functional impairment known as Dupuytren and Ledderhose diseases, respectively. Current treatments are noncurative and associated with significant morbidity. Here, we report on the outcomes of 5 patients with advanced disease, no longer surgical candidates, treated with sorafenib. Sorafenib exhibited an expected safety profile. All 5 patients demonstrated objective responses as evaluated by a decrease in tumor size and/or tumor cellularity from baseline and all 5 patients reported subjective pain relief and/or functional improvement. Mechanistically, immunohistochemistry revealed patchy positivity for PDGFRß, a known target of sorafenib. The outcomes of these 5 patients suggest the safety and efficacy of a relatively well-tolerated oral agent in the treatment of Dupuytren and Ledderhose diseases and suggest the need for future controlled studies.

Sensory innervation of the human palmar aponeurosis in healthy individuals and patients with palmar fibromatosis.

The human palmar aponeurosis is involved in hand proprioception, and it contains different sensory corpuscle morphotypes that serve this role. In palmar fibromatosis (classically referred to as Dupuytren's disease), the palmar aponeurosis undergoes fibrous structural changes that, presumably, also affect the nervous system, causing altered perception. We analysed the various sensory nerve formation morphotypes in the palmar aponeuroses of healthy subjects and patients with palmar fibromatosis. To do this, we used immunohistochemistry for corpuscular constituents and the putative mechanoproteins PIEZO2 and acid-sensing ion channel 2. Free nerve endings and Golgi-Mazzoni, Ruffini, paciniform and Pacinian corpuscles were identified in both the healthy and the pathological conditions. The densities of the free nerve endings and Golgi-Mazzoni corpuscles were slightly increased in the pathological tissues. Furthermore, the Pacinian corpuscles were enlarged and displayed an altered shape. Finally, there was also morphological and immunohistochemical evidence of occasional denervation of the Pacinian corpuscles, although no increase in their number was observed. Both PIEZO2 and acid-sensing ion channel 2 were absent from the altered corpuscles. These results indicate that the human palmar aponeurosis is richly innervated, and the free nerve endings and sensory corpuscles within the palmar aponeurosis undergo quantitative and qualitative changes in patients with palmar fibromatosis, which may explain the sensory alterations occasionally reported for this pathology.

Measuring functional outcome in Dupuytren's disease: A systematic review of patient-reported outcome measures.

BACKGROUND: Functional impairments related to Dupuytren's disease (DD) can be assessed using patient-reported outcome measures (PROMs). A systematic review was published in 2013 on outcome measures for assessing treatment in individuals with DD; however, several articles have since been published on this matter. PURPOSE: To conduct a systematic review to analyze the quality and content of the evidence on the psychometric properties of PROMs used in individuals with DD. STUDY DESIGN: Systematic review. METHODS: CINAHL, EBM reviews, Embase, Medline, and Web of Science were searched to identify studies evaluating the psychometric properties of PROMs used with individuals with DD. All studies retained were appraised by two independent assessors using two validated critical appraisal tools. RESULTS: Fifteen articles on the psychometric properties of 10 PROMs were included. Construct validity and responsiveness were the most studied. Eighty percent of the studies were of good to very good methodological quality according to MacDermid's Critical appraisal checklist for psychometric articles, whereas 67% of the studies comported risks of bias according to the COSMIN checklist. Of the 10 PROMs, three were specifically developed for DD but remain mostly under-studied for their psychometric properties (≤ 2 studies for the SDSS and DIF-CHUM). The QuickDASH, MHQ, BriefMHQ, and URAM present moderate to good convergent validity. Test-retest reliability was found to be good for the MHQ, briefMHQ, URAM, SDSS, SF-36, and the multi-attribute of the HUI-3. The MHQ and BriefMHQ are highly responsive. CONCLUSION: There is a need for more psychometric studies on the PROMs used with individuals with DD. However, to date, the results included in this systematic review support that the MHQ and briefMHQ are the PROMs with the most acceptable psychometric properties.

Biomimetic analyses of interactions between macrophages and palmar fascia myofibroblasts derived from Dupuytren's disease reveal distinct inflammatory cytokine responses.

Dupuytren's disease (DD) is a common and heritable fibrosis of the hand. It is characterized by the shortening and thickening of the palmar fascia into myofibroblastic nodules that can progress to palmar-digital contractures and permanent loss of dexterity. Molecular analyses of DD tissues and the presence of inflammatory cell infiltrates suggest a pathogenesis initiated by a proinflammatory fascial milieu that promotes myofibroblast activation and palmar fascia contractures. However, the relative contributions of vascular and/or tissue derived immune system cells and cytokine-sensitive stromal myofibroblasts to the development of this proinflammatory microenvironment are poorly understood. To gain insights into this process, we have developed and tested a collagen-based 3D tissue biomimetic co-culture system to assess paracrine interactions between THP-1-derived pro-inflammatory macrophages and primary human palmar fascia myofibroblasts (PFMs). We observed significant and reproducible impacts of collagen-adherent macrophage and PFM co-cultures on the cytokine gene expression profiles of these cells compared to their respective monocultures, and significant changes to the resulting cytokine milieu in their shared culture media, notably TNF and IL-6. Our findings are consistent with central roles for PFMs in cytokine production and immunoregulation of the pro-inflammatory milieu hypothesized to promote DD development.

Is Dupuytren's disease an occupational illness?

BACKGROUND: There is growing evidence for the risk of Dupuytren's disease (DD) from occupational exposure. For workers exposed to hand-transmitted vibrations (HTVs) and heavy manual work (HMW) who develop the disease, the inclusion of DD in hand-arm vibration syndrome and diseases of skeletal muscle overload could be beneficial for compensation purposes. AIMS: To assess the risk of DD in workers exposed to HTVs and HMW, and to evaluate the length of exposure times that may significantly affect the development of DD. METHODS: This study included male workers in Kosice, Slovak Republic. Participants were divided into three groups: those exposed to HTVs, those exposed to HMW and controls. We evaluated the association between DD and HTVs, HMW, cardiovascular diseases, metabolic diseases, epilepsy, smoking and alcohol consumption for all groups. We also compared the length of exposure time to HTV and HMW between workers with and without DD. RESULTS: The sample was comprised of 515 men, with 13% suffering from DD. Significant associations were found between DD and HTVs (OR 4.59 [95% CI 2.05-10.32]) and HMV (OR 3.10 [95% CI 1.21-7.91]). Highly significant associations were found between DD and older ages and alcohol consumption as well. No associations were found for the other variables. Exposure times greater than 15 years significantly increased the risk for DD (P < 0.01). CONCLUSIONS: This study confirms a significant association between DD and both HTVs and HMW after long exposures. We suggest that DD should be considered as an occupational disease.

Self-Perceived Hand Normality Before and After Surgical Treatment of Dupuytren Contracture.

PURPOSE: To describe patients' self-reported hand normality before and after surgery for Dupuytren contracture and to determine whether this metric could be used as an adjunct to determine the success of surgery. METHODS: Preoperative and 1-year postoperative Quick-Disabilities of the Arm, Shoulder, and Hand and EuroQol 5-Dimensions 5-level scores were collected prospectively over 5 years. Patients were asked "How normal is your hand?" Scores were recorded on a 100-point visual analog scale. Outcomes were available for 296 patients (77%). RESULTS: Median hand normality score improved significantly from 50 to 86 after surgery. Effect size of the change in normality was 1.2 SDs. The change in normality score correlated significantly with the Quick-Disabilities of the Arm, Shoulder, and Hand score. No significant floor or ceiling effects were observed. CONCLUSIONS: This study introduced the concept of self-perceived hand normality in Dupuytren disease. Hand normality improved after surgery for Dupuytren disease, and this score performed favorably compared with preexisting outcome measures, which suggests it may be a useful adjunct to gauge the success of surgery. CLINICAL RELEVANCE: This study introduces the concept of self-perceived hand normality in patients undergoing surgery for Dupuytren disease and quantifies improvement observed after surgery.

Content validity and responsiveness of the Patient-Specific Functional Scale in patients with Dupuytren's disease.

INTRODUCTION: Patient-reported outcome measures have become the standard tool for reflecting the patient's perspective on their treatment outcome for a wide variety of hand conditions. The Patient-Specific Functional Scale (PSFS), is an individualized questionnaire that enables patients to specify those activities with which they have difficulty in daily life. PURPOSE OF THE STUDY: This study aims to determine the content validity and responsiveness of the PSFS compared with the Michigan Hand Questionnaire (MHQ) in patients with Dupuytren's disease. STUDY DESIGN: Multicentre inception cohort. METHODS: Patients with Dupuytren's disease being treated with percutaneous needle aponeurotomy, limited fasciectomy, or skin graft were selected from a database with routine outcome measurements in usual care. To assess content validity of the PSFS, the activities specified by patients were classified into the International Classification of Function core set for hand conditions. The standardized response mean is calculated for the pre- and post-change scores of the PSFS to evaluate responsiveness. RESULTS: Three hundred and eight patients were analyzed before and three months after treatment. Content validity of the PSFS was appropriate because 95% of all items could be classified into the International Classification of Function activities and participation domain. The standardized response mean of the PSFS was 1.0 (95% confidence interval, 0.86-1.2), which was substantially larger than the standardized response mean of the MHQ score 0.58 (95% confidence interval, 0.42-0.74). DISCUSSION: The PSFS is a content-valid questionnaire which may be more responsive to change than a fixed-item instrument such as the MHQ in patients with Dupuytren's disease. CONCLUSIONS: The PSFS is a valuable tool to set therapy goals and evaluate the progress over time in patients with Dupuytren's disease.

Integrative analysis of Dupuytren's disease identifies novel risk locus and reveals a shared genetic etiology with BMI.

Dupuytren's disease is a common inherited tissue-specific fibrotic disorder, characterized by progressive and irreversible fibroblastic proliferation affecting the palmar fascia of the hand. Although genome-wide association study (GWAS) have identified 24 genomic regions associated with Dupuytrens risk, the biological mechanisms driving signal at these regions remain elusive. We identify potential biological mechanisms for Dupuytren's disease by integrating the most recent, largest GWAS (3,871 cases and 4,686 controls) with eQTLs (47 tissue panels from five consortia, total n = 3,975) to perform a transcriptome-wide association study. We identify 43 tissue-specific gene associations with Dupuytren's risk, including one in a novel risk region. We also estimate the genome-wide genetic correlation between Dupuytren's disease and 45 complex traits and find significant genetic correlations between Dupuytren's disease and body mass index (BMI), type II diabetes, triglycerides, and high-density lipoprotein (HDL), suggesting a shared genetic etiology between these traits. We further examine local genetic correlation to identify 8 and 3 novel regions significantly correlated with BMI and HDL respectively. Our results are consistent with previous epidemiological findings showing that lower BMI increases risk for Dupuytren's disease. These 12 novel risk regions provide new insight into the biological mechanisms of Dupuytren's disease and serve as a starting point for functional validation.