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The Oncologist Mar 2022Palmar 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...
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 PDGFRβ, 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.
Topics: Dupuytren Contracture; Fibromatosis, Plantar; Humans; Pain; Pain Management; Sorafenib
PubMed: 35274715
DOI: 10.1093/oncolo/oyab050 -
Medicina (Kaunas, Lithuania) Jun 2020Dupuytren's contracture is a chronic fibroproliferative hand disorder with a varying pattern of genetic predisposition across different regions and populations....
Dupuytren's contracture is a chronic fibroproliferative hand disorder with a varying pattern of genetic predisposition across different regions and populations. Traumatic events have been found to have influence on the development of this illness and are likely to trigger different clinical forms of this disease. The aim of this study was to evaluate the phenomenon of development of Dupuytren's contracture (DC) following an acute injury to the hand, and to observe the incidence and clinical diversity of such cases in daily clinical practice. We collected data of patients presenting with primary Dupuytren's contracture in the Lithuanian population and evaluated the occurrence and clinical manifestation of this specific type of DC, arising following acute hand trauma. The diagnosis of DC was based on clinical signs and physical examination. Digit contractures were measured by goniometry, and the staging was done according to Tubiana classification. Injury-induced (injury-related) cases were identified using the "Criteria for recognition of Dupuytren's contracture after acute injury" (established by Elliot and Ragoowansi). 29 (22%) of a total of 132 cases were injury-induced DCs. Twenty-six of 29 patients in this group presented with stage I-II contractures. Duration of symptoms was 6 (SD 2.2) and 3.8 (SD 2.2) years in the injury-related and injury-unrelated DC groups, respectively. Mean age on the onset of symptoms in the injury-induced and non-injury-induced groups was 52 (SD 10.7) and 56 (SD 10.9), respectively. Patients from both groups expressed strong predisposition towards development of DC. Around one-fifth of patients seeking treatment for primary Dupuytren's contracture seemed to suffer from injury-induced Dupuytren's contracture. We noted that injury to the wrist and hand seems to trigger the development of less progressive Dupuytren's contracture in younger age. Prospective randomized studies are required to confirm our findings.
Topics: Adult; Aged; Dupuytren Contracture; Female; Genetic Predisposition to Disease; Humans; Incidence; Male; Middle Aged; Prospective Studies
PubMed: 32629785
DOI: 10.3390/medicina56070323 -
Hand (New York, N.Y.) Nov 2022With numerous treatment modalities available, it is unclear whether the treatment of recurrent Dupuytren disease is as effective as its initial treatment. We aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With numerous treatment modalities available, it is unclear whether the treatment of recurrent Dupuytren disease is as effective as its initial treatment. We aimed to investigate the outcomes of management of recurrent Dupuytren contracture.
METHODS
Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, MEDLINE, Embase, PubMed, CINAHL, and Cochrane Central Register of Controlled Trials were searched from their inception to April 2020. Studies of patients aged above 18 years undergoing treatment for recurrent Dupuytren contractures were included. The Risk Of Bias In Non-randomized Studies-of Interventions tool was used for quality assessment. The study was registered with Open Science Foundation.
RESULTS
A systematic review identified 12 studies: 311 patients with 224 affected digits-index (n = 5; 2.2%), long (n = 17; 7.6%), ring (n = 57; 25.4%), small (n = 112; 50%), and unspecified (n = 33; 14.7%); of these, there were 76 metacarpophalangeal joints (MCPJ; 45.5%), 90 proximal phalangeal joints (PIPJ; 53.9%), and 1 distal interphalangeal joint (0.6%). Previous treatment included the following: percutaneous needle aponeurotomy (n = 103 of 311 patients; 33.1%), collagenase clostridium histolyticum-injection (CCH; n = 75 of 311; 24.1%), limited fasciectomy (LF) ± skin graft (n = 83 of 311; 26.7%), fasciotomy (n = 1 of 311; 0.3%), and unspecified (n = 64 of 311; 20.6%). Recurrence was treated by percutaneous needle aponeurotomy (n = 68 of 311 patients; 21.9%); CCH injection (n = 53 of 311; 17.0%); aponeurotomy or dermofasciectomy or LF (n = 176 of 311; 56.6%); ray/digit amputation (n = 8 of 311; 2.6%); and PIPJ arthrodesis (n = 6 of 293; 2.0%). Range of motion was improved by 23.31° (95% confidence interval [CI] = 13.13°-33.50°; = 67%; = .05) and 15.49° (95% CI = 2.67°-28.31°; = 76%; = .01) for MCPJ and PIPJ, respectively.
CONCLUSIONS
There is low level of evidence that both surgical and nonsurgical treatments provide clinically important improvements for recurrent Dupuytren contracture.
Topics: Humans; Aged; Dupuytren Contracture; Microbial Collagenase; Treatment Outcome; Fasciotomy; Injections
PubMed: 33618538
DOI: 10.1177/1558944721994220 -
BMC Musculoskeletal Disorders May 2011In view of the conflicting opinions published, a meta-analysis was undertaken on epidemiological studies in order to assess any association between Dupuytren's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In view of the conflicting opinions published, a meta-analysis was undertaken on epidemiological studies in order to assess any association between Dupuytren's contracture and work exposure.
METHODS
Using the key words: "occupational disease", "work" and "Dupuytren contracture" without limitation on language or year of publication, epidemiological studies were selected from four databases (Pub-Med, Embase, Web of science, BDSP) after two rounds (valid control group, valid work exposure). A quality assessment list was constructed and used to isolate papers with high quality methodological criteria (scores of 13 or above, HQMC). Relevant associations between manual work, vibration exposure (at work) and Dupuytren's contracture were extracted from the articles and a metarisk calculated using the generic variance approach (meta-odds ratios, meta-OR).
RESULTS
From 1951 to 2007, 14 epidemiological studies (including 2 cohort studies, 3 case-control studies, and 9 cross-sectional studies/population surveys) were included. Two different results could be extracted from five studies (based on different types of exposure), leading to 19 results, 12 for manual work (9 studies), and 7 for vibration exposure (5 studies). Six studies met the HQMC, yielding 9 results, 5 for manual work and 4 for vibration exposure. Five studies found a dose-response relationship. The meta-OR for manual work was 2.02[1.57;2.60] (HQMC studies only: 2.01[1.51;2.66]), and the meta-OR for vibration exposure was 2.88 [1.36;6.07] (HQMC studies only: 2.14[1.59;2.88]).
CONCLUSION
These results support the hypothesis of an association between high levels of work exposure (manual work and vibration exposure) and Dupuytren's contracture in certain cases.
Topics: Dupuytren Contracture; Humans; Occupational Diseases; Occupational Exposure; Odds Ratio; Risk Assessment; Risk Factors; Vibration
PubMed: 21575231
DOI: 10.1186/1471-2474-12-96 -
The Journal of Hand Surgery, European... Feb 2015Safety was evaluated for collagenase Clostridium histolyticum (CCH) based on 11 clinical trials (N = 1082) and compared with fasciectomy data in a structured literature... (Review)
Review
Safety was evaluated for collagenase Clostridium histolyticum (CCH) based on 11 clinical trials (N = 1082) and compared with fasciectomy data in a structured literature review of 48 European studies (N = 7727) for treatment of Dupuytren's contracture. Incidence of adverse events was numerically lower with CCH vs. equivalent complications from fasciectomy (median [range] incidence), including nerve injury (0% vs. 3.8% [0%-50+%]), neurapraxia (4.4% vs. 9.4% [0%-51.3%]), complex regional pain syndrome (0.1% vs. 4.5% [1.3%-18.5%]) and arterial injury (0% vs. 5.5% [0.8%-16.5%]). Tendon injury (0.3% vs. 0.1% [0%-0.2%]), skin injury (16.2% vs. 2.8% [0%-25.9%]) and haematoma (77.7% vs. 2.0% [0%-25%]) occurred at a numerically higher incidence with CCH than surgery. Adverse events in CCH trials not reported after fasciectomy included peripheral oedema; extremity pain; injection site pain, haemorrhage and swelling; tenderness; pruritus and lymphadenopathy. CCH-related adverse events were reported as predominantly injection-related and transient. These results may support clinical decision-making for treatment of Dupuytren's contracture.
Topics: Dupuytren Contracture; Fasciotomy; Humans; Injections, Intralesional; Microbial Collagenase; Treatment Outcome
PubMed: 24698851
DOI: 10.1177/1753193414528843 -
Cureus Dec 2021Introduction Dupuytren's contracture is a disabling and progressive flexion contracture of the hand that is often treated by a surgical release. Collagenase clostridium...
Introduction Dupuytren's contracture is a disabling and progressive flexion contracture of the hand that is often treated by a surgical release. Collagenase clostridium histolyticum injection (CCH-I) was introduced to the UK in 2011 as an alternative and less invasive treatment for contracture. The purpose of this study was to evaluate the cost-effectiveness and patient-reported outcome measures (PROMs) of treating Dupuytren's contracture with collagenase compared to surgery. Methods A retrospective review identified 151 patients who underwent CCH-I (n=94), limited fasciectomy (LF; n=38) and percutaneous needle fasciotomy (PNF; n=19). Outcomes included PROMs (satisfaction, QuickDASH), complication rates (recurrence, reintervention) and direct costs. Results Standardised treatment costs for CCH-I, LF and PNF were £1,125.82, £3,438.28 and £1,143.32 respectively. Collagenase presented a cost-benefit of £88,205 had the LF/PNF group undergone CCH-I. At a mean six-year follow-up, there were no significant differences in complication rates (=0.621) or QuickDASH scores (p=0.157). Collagenase-treated patients reported the highest satisfaction and lowest recurrence rates. Discussion Collagenase presents a significant cost reduction with superior PROMs relative to surgery for treating single-digit contracture. Conclusion Outpatient CCH-I is a cost-effective treatment with fewer clinical encounters, a similar risk profile to LF/PNF and high levels of patient satisfaction, which warrants serious consideration in light of overburdened waiting lists due to COVID-19.
PubMed: 35070563
DOI: 10.7759/cureus.20530 -
Occupational and Environmental Medicine Apr 2014The relation between Dupuytren's contracture and occupational exposure to hand-transmitted vibration (HTV) has frequently been debated. We explored associations in a...
AIMS
The relation between Dupuytren's contracture and occupational exposure to hand-transmitted vibration (HTV) has frequently been debated. We explored associations in a representative national sample of workers with well-characterised exposure to HTV.
METHODS
We mailed a questionnaire to 21 201 subjects aged 16-64 years, selected at random from the age-sex registers of 34 general practices in Great Britain and to 993 subjects chosen randomly from military pay records, asking about occupational exposure to 39 sources of HTV and about fixed flexion contracture of the little or ring finger. Analysis was restricted to men at work in the previous week. Estimates were made of average daily vibration dose (A(8) root mean squared velocity (rms)) over that week. Associations with Dupuytren's contracture were estimated by Poisson regression, for lifetime exposure to HTV and for exposures in the past week >A(8) of 2.8 ms(-2) rms. Estimates of relative risk (prevalence ratio (PR)) were adjusted for age, smoking status, social class and certain manual activities at work.
RESULTS
In all 4969 eligible male respondents supplied full information on the study variables. These included 72 men with Dupuytren's contracture, 2287 with occupational exposure to HTV and 409 with A(8)>2.8 ms(-2) in the past week. PRs for occupational exposure to HTV were elevated 1.5-fold. For men with an A(8)>2.8 ms(-2) in the past week, the adjusted PR was 2.85 (95% CI 1.37 to 5.97).
CONCLUSIONS
Our findings suggest that risk of Dupuytren's contracture is more than doubled in men with high levels of weekly exposure to HTV.
Topics: Adolescent; Adult; Dupuytren Contracture; Fingers; Hand; Hand-Arm Vibration Syndrome; Humans; Male; Middle Aged; Occupational Exposure; Prevalence; Range of Motion, Articular; Risk Factors; Surveys and Questionnaires; United Kingdom; Vibration; Young Adult
PubMed: 24449599
DOI: 10.1136/oemed-2013-101981 -
Annals of the Rheumatic Diseases Apr 1986Reported alcohol consumption was quantified and scored by a validated questionnaire administered by an interviewer to 64 patients (10 female) with Dupuytren's...
Reported alcohol consumption was quantified and scored by a validated questionnaire administered by an interviewer to 64 patients (10 female) with Dupuytren's contracture (DC) before hand surgery and to 89 controls (44 female) admitted for other hand or foot surgery. Serum urate (SUA), gamma-glutamyl transferase (GGT), and mean red cell volume (MCV) were measured on admission. Thirteen of 54 men with DC reported current daily alcohol intake of 40 g or more compared with one of 45 male controls (p = 0.0001). Two of 10 women with DC (but none of 44 controls) admitted consuming at least 40 g alcohol daily (p = 0.03). MCV was higher in men (but not women) with DC than in controls (p less than 0.0005). Current alcohol consumption score of patients with DC correlated with SUA (r = 0.308, p less than 0.05), MCV (r = 0.44, p less than 0.01), and GGT (r = 0.54, p much less than 0.001) on admission. DC among men is strongly associated with heavy drinking, reflected both in self reporting and haematological data.
Topics: Aged; Alcohol Drinking; Dupuytren Contracture; Erythrocyte Indices; Female; Humans; Male; Middle Aged; Sex Factors; Uric Acid; gamma-Glutamyltransferase
PubMed: 2871816
DOI: 10.1136/ard.45.4.304 -
Communications Biology Nov 2023Dupuytren's contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide...
Dupuytren's contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signalling dysregulation in the onset and progression of Dupuytren's contracture remains unclear. Here, using a fibrosis mouse model and clinical samples of human Dupuytren's contractures, we demonstrate that the activation of Wnt/β-catenin signalling in Tppp3-positive cells in the dermis of the paw is associated with the development of fibrosis. Fibrosis development and progression via Wnt/β-catenin signalling are closely related to stromal cell-macrophage interactions, and Wnt/β-catenin signalling activation in Tppp3-positive stromal cells causes M2 macrophage infiltration via chemokine Cxcl14, resulting in the formation of a TGF-β-expressing fibrotic niche. Inhibition of Cxcl14 mitigates fibrosis by decreasing macrophage infiltration. These findings suggest that Cxcl14-mediated stromal cell-macrophage interaction is a promising therapeutic target for Wnt/β-catenin-induced fibrosis.
Topics: Animals; Mice; Humans; Dupuytren Contracture; beta Catenin; Ligands; Wnt Signaling Pathway; Fibrosis
PubMed: 37980373
DOI: 10.1038/s42003-023-05558-8 -
BMC Medical Genomics Sep 2023The correlation between smoking and alcohol consumption and the development of Dupuytren's disease (DD) has been acknowledged. However, the definitive causal...
BACKGROUND
The correlation between smoking and alcohol consumption and the development of Dupuytren's disease (DD) has been acknowledged. However, the definitive causal relationship between these two factors and DD remains elusive. In order to establish a causal connection, we employed the two-sample Mendelian randomization method to evaluate the relationship between smoking and alcohol consumption and DD.
METHODS
Based on publicly available genome-wide association studies (GWAS), two-sample univariate MR analyses were performed to assess the causal effects of drinks per week, cigarettes per day, smoking initiation, age of initiation, and smoking cessation on DD. We used inverse variance weighted (IVW) to generate the primary results for the MR analysis. Furthermore, we performed sensitivity MR analyses based on various methods to assess the robustness of estimations. Bidirectional MR analyses were used to study the interaction between smoking and alcohol consumption. Multivariate MR analyses were used to obtain independent causal effects of smoking or drinking on DD.
RESULTS
Our two-sample MR, which was predominately based on IVW, revealed a causal relationship between drinks per week and DD (OR = 2.948, 95%CI: 1.746-4.975, P = 5.16E-05). In addition, there is no causal association between cigarettes per day, smoking initiation, age of initiation, smoking cessation and DD. Similar conclusions were reached by other MR methods. The results of the bidirectional MR analyses showed that the causal relationships between age of initiation and drinks per week were robust and significant. Multivariate MR results indicated that the causal effect of alcohol consumption on DD was independent of smoking.
CONCLUSION
Our Mendelian Randomization study indicated that there is a causality between drinking alcohol and DD, but no such causality was found between smoking and DD. This is the first study to prove that drinking alcohol could cause DD. This could help people who are trying to prevent DD from happening in the first place.
Topics: Humans; Smoking; Dupuytren Contracture; Genome-Wide Association Study; Mendelian Randomization Analysis; Ethanol; Alcohol Drinking
PubMed: 37679690
DOI: 10.1186/s12920-023-01650-4