Abstract
Dupuytren’s disease (DD) is a common chronic hand condition that affects patients worldwide. Presenting with palpable fibrotic nodules, the disease leads to progressive and irreversible flexion of digits, affecting patients’ hand function, impairing daily activities and potentially reducing the quality of life. Management techniques are primarily corrective and do not address the biological mechanisms underlying disease pathogenesis and progression. While non-surgical interventions are used to manage early stage DD, advanced disease requires surgical correction. This review provides an overview of the epidemiology and risk factors associated with DD and the latest research on the mechanisms underlying its progression. It summarizes the main non-surgical and surgical corrective options currently available and discusses the future of early stage DD treatment.
Introduction
Dupuytren’s disease (DD) is a chronic fibroproliferative disease that affects the palmar fascia (Gudmundsson et al., 2000; Karbowiak et al., 2021; Verhoekx et al., 2013). It is characterized by the formation of fibrotic nodules on the palmar surface of the hand, which may be tender to touch. In a minority of patients, disease progression leads to the formation of fibrous cords crossing the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, causing flexion deformities (Alser et al., 2020a). Joint contractures can lead to significant loss of hand function, contributing to a reduced quality of life (Van Den Berge et al., 2021; Wilburn et al., 2013).
Corrective surgical interventions in the late stages of the disease are the mainstay of treatment for DD (Bayat and McGrouther, 2006). However, it is an incurable condition with a high risk of recurrence after any intervention (Alser et al., 2020a; Van Den Berge et al., 2021). Current research is focusing on early treatment and the molecular biology of DD to target disease prevention (Nanchahal et al., 2022; Nanchahal and Chan, 2023). We review the latest knowledge on the epidemiology, genetics and biology of DD and discuss its clinical management and future research.
Epidemiology and risk factors
Epidemiology
The occurrence of DD varies globally, predominantly affecting individuals of European descent (Bayat and McGrouther, 2006; Hindocha et al., 2009). A recent genome-wide association meta-analysis delving into the potential underlying factors for this distribution posits that it may be linked to the inheritance of Neanderthal-origin haplotypes and variants of archaic humans who primarily inhabited Western and Eastern Eurasia (Ågren et al., 2023). Reported prevalence rates have ranged widely from 0.2 to 56% (Hindocha et al., 2009; Lanting et al., 2013) with a recent systematic review establishing a global prevalence of 8.2% (Salari et al., 2020). This variability in prevalence rates is attributed, in part, to differences in study populations, including varying definitions of diagnosis, demographics, geographical location, participant health status, the presence of specific genetic variants within populations, comorbidities and risk factors (Hindocha et al., 2009; Lanting et al., 2013).
Risk factors
Dupuytren’s disease is a complex disease in which a combination of genetic and non-genetic factors gives rise to the disease phenotype.
Non-genetic and environmental risk factors
Many non-genetic and environmental risk factors predispose individuals to DD and have recently been summarized in a systematic review (Alser et al., 2020b). Risk factors supported by strong evidence include increasing age, being male, high cholesterol, diabetes mellitus and lifestyle choices such as increased alcohol consumption and cigarette smoking (Alser et al., 2020b). Coeliac disease has also been recognized as a risk factor for the development of DD, particularly in women and older people (Yuan et al., 2025). Conversely, an increased body mass index is a protective factor (Alser et al., 2020b; Hacquebord et al., 2017).
Age is a highly significant factor influencing prevalence rates (Broekstra et al., 2022). Lanting et al. (2013) observed an increase in prevalence with advancing age in several Western countries, reporting rates of 12, 21 and 29% in individuals aged 55, 65 and 75 years, respectively. This association is partially influenced by biological sex, with men below the age of 54 years more likely to develop DD than women, with a ratio of 4:1. However, as age increases, this ratio approaches a more equal distribution of 1:1 (Anthony et al., 2008).
Increased exposure to manual labour and previous hand trauma have been associated with an increased risk of DD, although the connection between hand trauma and the disease has been a subject of debate owing to the varying definitions of hand trauma and ‘heavy manual work’ (Alser et al., 2020b; Descatha et al., 2014; Palmer et al., 2014). A population-based cohort study clarified this association and showed a distinct positive dose–response relationship, highlighting the correlation between cumulative manual work exposure and DD occurrence (Van Den Berge et al., 2023). (Van Den Berge et al., 2023). Similar trends have been observed with other types of hand trauma, including sports that cause significant repetitive hand strain, distal radius fractures and surgery for trigger finger and carpal tunnel release (Novo et al., 2025).
Comorbidities such as hypercholesterolaemia, diabetes mellitus, liver disease and epilepsy have been linked to DD (Alser et al., 2020b; Arafa et al., 1992; Broekstra et al., 2018; Sanderson et al., 1992). Lifestyle factors, such as dose-dependent alcohol consumption, are strongly associated with DD (Godtfredsen et al., 2004; Wang et al., 2023). Increased alcohol intake may predispose patients to develop a more aggressive form of DD with multiple digit involvement (Morelli et al., 2017). Similarly, several studies have identified cigarette smoking as a risk factor for DD (Alser et al., 2020b; Godtfredsen et al., 2004; Gudmundsson et al., 2000), although a recent Mendelian randomization study failed to support this association (Wang et al., 2023).
Dupuytren’s disease has been linked to increased mortality, including an increased risk of cancer; however, this association only becomes apparent 12 years after diagnosis (Kuo et al., 2020). Indeed, another study with a median follow-up of 5 years showed a survival benefit of DD (Van Den Berge et al., 2024). Therefore, it remains unclear whether DD is associated with any change in mortality and this area requires further investigation.
Genetic risk factors
Dupuytren’s disease is a highly heritable disease as evidenced by findings from family and twin studies (Lanting et al., 2013; Larsen et al., 2015). Genetic influences on DD have been reported by investigating familial clustering, molecular genetics and population studies (Dolmans et al., 2011; Finsen et al., 2002; Hu et al., 2005). Two studies revealed a positive family history in 41–47% of patients with the disease, as well as a 2.9–4.5 times higher risk of DD in individuals with an affected sibling compared with the general population (Capstick et al., 2013; Hindocha et al., 2006). Furthermore, a study of over 30,000 monozygotic and dizygotic twin pairs in Denmark showed a strong genetic influence with heritability estimates of 80–82% for both men and women (Larsen et al., 2015).
Over the past decade, numerous candidate genes potentially implicated in DD have emerged from comprehensive profiling studies exploring the condition at the genomic, transcriptomic and proteomic levels (Shih et al., 2012). A European genome-wide association study (GWAS) identified nine regions associated with the condition, all located in the non-protein-coding regions and primarily associated with the WNT signalling pathway (Dolmans et al., 2011). A subsequent GWAS identified 17 additional locations, with additional links to extracellular matrix remodelling and inflammatory pathways (Ng et al., 2017). In a more recent European GWAS and meta-analysis, the Hedgehog and Notch signalling pathways were implicated which also identified a significant genetic correlation with frozen shoulders (Ågren et al., 2023; Riesmeijer et al., 2024). Furthermore, a polygenic risk score was shown to strongly correlate with the risk of developing DD, which may help identify individuals at high risk of disease in future studies aimed at prevention. These findings highlight the multifaceted genetic underpinnings of DD and advance our knowledge of its pathogenesis and potential therapeutic targets.
Dupuytren’s diathesis
The progression of DD is variable and certain clinical characteristics in patients are associated with a more aggressive disease course or diathesis. Dupuytren’s diathesis includes early disease onset, bilateral involvement, positive family history and the presence of ectopic lesions (knuckle pads, Ledderhose disease and Peyronie’s disease) (Hueston and McFarlane, 1963). These criteria have been expanded to include men, early onset of disease at an age younger than 50 years and the presence of knuckle pads (Hindocha et al., 2006).
More recently, a study showed that patients with an age of disease onset <50 years, a positive family history and the presence of knuckle pads are significantly more likely to carry genetic risk variants for DD (Dolmans et al., 2012). Patients with all five diathesis features (men, bilateral disease, knuckle pads, age at onset <50 years and positive family history) have a 71% risk of recurrent DD compared with a baseline risk of 23% (Hindocha et al., 2006).
Clinical presentation
Dupuytren’s disease usually starts in the palm and subsequently progresses distally into the fingers. The most common presenting complaints are a palpable nodule and loss of dexterity, including a decreased range of motion and a feeling of stiffness when mobilizing the affected hand. Although the ring and little finger rays are the most commonly affected, DD can also present in other fingers and the thumbs (Karbowiak et al., 2021). The disease presents bilaterally in 46–54% of cases (Lanting et al., 2013; Mansur et al., 2018).
The hallmark clinical signs of DD are the presence of skin pits and nodules followed by the formation of fibrotic cords which gradually restrict finger extension. The thickening of the palmar fascia and laying down of abnormal collagen leads to skin adherence to underlying tissues and reduced skin mobility (Broekstra et al., 2022). Fibrotic cords, which join the dermis to the palmar fascia, contract to form micro-cords producing skin pitting, creasing and dimpling typically distal to the distal palmar crease. This pattern of pitting is an early pathognomonic sign of DD (Rayan, 2007).
In the early phase of the disease, nodules can be tender to palpation (Walthall et al., 2019). In both hands and all finger rays, nodules progress slowly during the course of the disease (Broekstra et al., 2022). As nodules grow, they can form fibrotic cords which thicken and contract over a period of months to years, leading to deformities that prevent straightening of the joints involved (Gudmundsson et al., 2001; Shaw et al., 2007). In some cases, nodules remain static or regress spontaneously (Broekstra et al., 2022).
Disease progression
A cross-sectional study by Lanting et al. (2013) found that most patients (over 80%) with DD have early-stage disease without any finger contractures, suggesting that progression is the exception rather than the rule. Indeed, longitudinal studies show 20% of patients have progressive disease at 7 years and 35% at 18 years (Van Den Berge et al., 2021; Gudmundsson et al., 2001).
Classifying disease progression
The use of classification systems to identify the degree of progression of DD has been useful for recommending treatment, predicting surgical outcomes and for understanding how the disease develops. However, the lack of a standardized system can pose a barrier to direct comparison of clinical studies (Akhavani et al., 2015).
Some classification systems focus on clinical signs, such as Iselin’s scale or Tubiana’s staging and describe the progression of contracture across the hand and joints (Augoff et al., 2006; Hindocha et al., 2008). Dias and Braybrooke (2006) described five stages: (1) no contraction; (2) mild contraction of the MCP only; (3) mild PIP joint (PIPJ) contracture or moderate MCP contracture; (4) moderate PIP contracture; and (5) Severe contracture of both MCP and PIP joints.
Luck’s (1959) classification, updated by Lam et al., (2010), focusses on the histopathological staging of DD. It identifies three key phases: the proliferative stage, the involutional (contractile) stage and the residual stage. In each stage, the composition and orientation of myofibroblasts and fibroblasts vary in relation to stages of tissue remodelling, with myofibroblasts being the primary cell responsible for Luck’s involutional stage (Gokel and Huebner, 1977). Lam et al. (2010) showed a decrease in Type III collagen as the stages progressed and suggested a staging system based on these findings.
Fibroblast-to-myofibroblast transition
Connective tissue throughout the body is primarily composed of fibroblasts embedded in a complex network of extracellular matrix (ECM) proteins. The fibroblasts are responsible for homeostatic regulation of the ECM through the production of structural proteins (such as collagen), adhesive proteins and ground substance (Kendall and Feghali-Bostwick, 2014). Several pathways can lead to increased fibroblast proliferation and signalling, referred to as fibroblast ‘activation’ (D’Urso and Kurniawan, 2020). When this takes place, fibroblasts can differentiate into myofibroblasts: a process also referred to as ‘fibroblast-to-myofibroblast transition’ (D’Urso and Kurniawan, 2020). Layton et al. (2022) noted a close interaction between endothelial and fibroblast cells, highlighting the role of the perivascular niche in fibrosis. As well as resident fibroblasts, other cell types in DD have been posed as myofibroblast precursors: these include pericytes (Layton et al., 2022), adipocytes (Karkampouna et al., 2016), peri-nodular dermal cells (Iqbal et al., 2012) and stem cells (On et al., 2017). Also, Layton et al. (2022) identified subsets of pericytes transitioning to myofibroblasts using CyTOF and scRNA-seq, observing intermediate cell states.
Myofibroblasts are specialized stromal cells recognized as the pathogenic driving force in many fibrotic conditions, including DD (D’Urso and Kurniawan, 2020; Lambi et al., 2023). Myofibroblasts are identified by the presence of α-smooth muscle actin, a cytoskeletal protein used as a marker of the cell type (Layton et al., 2020). Pathogenic myofibroblast activity leads to aberrant fibroproliferation and remodelling of palmar tissue through an interplay of molecular pathways (Layton et al., 2022). The myofibroblast sub-type involved in DD was identified by Dobie et al. (2022). This research used single-cell RNA sequencing to profile 35,250 cells from DD tissue, healthy dermis and non-pathogenic fascia. The sequencing revealed a pathogenic sub-population of mesenchymal cells, PDPN+/FAP+ myofibroblasts, found only in affected DD tissue. Upregulated pathways in this cell population were identified using transcriptomics. Understanding the biology of myofibroblasts, the ECM and their interactions is critical to designing new treatments in the future (Dobie et al., 2022).
Management and treatment
Expectant management
Early-stage DD is often managed purely through observation in a primary care setting. Expectant management is used when there is no functional impairment, the disease is stable and the patient is not in pain (Van Straalen et al., 2025). Most patients with nodules do not go on to develop a contracture and in some cases, nodules have been observed to regress completely (Hueston, 1992). One prospective cohort study found that after 7 years, 6.5% of patients no longer had palmar nodules. The mechanism behind this phenomenon is poorly understood (Van Den Berge et al., 2021). It is possible that this may occur at greater rates than is currently known – there may be members of the population who have barely perceptible nodules that regress before they are detected in a clinical setting.
Early-stage/non-operative treatment
Non-operative treatments targeting early-stage DD have been trialled, typically aiming to prevent or slow disease progression and alleviate pain. However, these treatments are only supported by limited evidence and are not endorsed by the National Institute of Care Excellence (Karbowiak et al., 2021). Patients may elect to try anecdotal treatments described on patient forums (such as acupuncture and stretching), but the efficacy of these treatments has not been substantiated (Karbowiak et al., 2021).
A recent systematic review grouped non-surgical interventions for early-stage DD into three categories – pharmacological approaches (such as oral, intramuscular, topical or intralesional steroids), radiotherapy and physical therapies (such as ultrasound, splinting, heat treatment and frictional massage) (Ball et al., 2016). A review in this journal explored recent data for these interventions (Nanchahal and Chan, 2023). Currently, the Dupuytren’s disease Evaluation of Preventative or Adjuvant Radiation Therapy multicentre randomized control trial is ongoing, with recent papers presenting secondary analysis data from the trial. Results showed mild to moderate adverse effects that were largely self-limiting (Burgess et al., 2025), minimal toxicity and possible quality of life improvement (Martin et al., 2026).
Corrective/operative treatment
As the disease progresses, patients may require surgery. Surgery has been the main method of treatment for DD for the last 200 years (Denkler et al., 2022). The aims of surgery include correcting the contracture and returning function to the hand, while maintaining low risks of recurrence and complications.
Initial indications for surgery include a positive Hueston’s tabletop test, where the patient is unable to place their hand flat on a table and evidence that the contracture significantly influences the patient’s quality of life (Karbowiak et al., 2021). The best practice pathway for Dupuytren’s Disease was developed by the BSSH using the ‘Getting if Right First Time’ platform, in collaboration with British Association of Plastic, Reconstructive and Aesthetic Surgeons and the British Orthopaedic Association. The listed thresholds for DD surgery are ‘flexion contracture of 30° or more at the MCPJ or 20° at the PIPJ’, ‘thumb contracture impairing function’, ‘previously failed non-operative management’ and ‘rapidly progressive disease’ (BSSH et al., 2023).
Common surgical procedures used to treat DD include percutaneous needle fasciotomy (PNF), limited fasciectomy (LF), dermofasciectomy (DF) and salvage procedures such as joint fusion and amputation. The complexity and risk of complications increase with more invasive procedures and multiple factors must be considered before choosing the type of treatment (Denkler et al., 2022). These include patient goals, age, lifestyle, severity of contracture, distribution of disease, diathesis factors and patient preference (Dahlin et al., 2012).
Alser et al. (2020a) carried out a longitudinal cohort study on data from 121,488 NHS patients who underwent 158,119 hand operations for DD, between 2007 and 2017. Overall, the probability of reoperation within 10 years decreased with more invasive treatments. This is linked to surgeon observations and clinical trial data showing that the more invasive the procedure (from PNF to LF to DF), the lower the risk of disease recurrence and the longer time-period until recurrence (Alser et al., 2020a; Dahlin et al., 2012). The studies showed that there were no serious systemic adverse events associated with PNF but there were with LF and DF at both 30 and 90 days after surgery. This was potentially linked to the use of general or regional anaesthesia in the latter two procedures (Alser et al., 2020a).
Percutaneous needle fasciotomy
Percutaneous needle fasciotomy is a minimally invasive procedure. It involves using a needle to mechanically disrupt the cord, which can then be ruptured by an extension force (Denkler et al., 2022). This can be carried out in an office-based, outpatient setting under local anaesthesia (Davis et al., 2020). For this reason, PNF is estimated to be seven times less expensive than limited fasciectomy (£111 vs. £777) (Davis et al., 2020).
Percutaneous needle fasciotomy is the least invasive corrective procedure available to patients, now that collagenase treatment is no longer available in many locations worldwide (Karbowiak et al., 2021). The initial recovery time is extremely rapid and shorter than that for other procedures (Van Rijssen et al., 2012; Rodrigues et al., 2015). In a randomized control study comparing LF and PNF outcomes at 6 weeks after surgery, patients who underwent PNF experienced better hand function and a lower degree of discomfort than LF patients and reduced complications (Mendelaar et al., 2019). The procedure is considered safe but there is a minor risk of skin tears and tendon rupture is very rare but does occasionally occur (Therkelsen et al., 2020). Undergoing PNF will not prevent patients from having other surgical procedures in the future, unlike DF and LF, which can lead to scarring, making subsequent surgical intervention more difficult and leading to a higher risk of complications (Denkler et al., 2022). The main disadvantage of PNF is the high rate of recurrence, with estimates ranging from 32 to 85% (Alser et al., 2020a; Van Rijssen et al., 2012). Overall, PNF may be the first treatment of choice for patients who are less concerned about recurrence, for example elderly patients and those who prefer a quicker return to function (Van Rijssen et al., 2012).
Percutaneous needle fasciotomy treatment has been developed further by Hovius et al. (2015) through the injection of lipoaspirate after the cord has been disrupted. This process is called percutaneous aponeurotomy and lipofilling (PALF). Although results were promising after a year, the procedure is not commonly used because of high long-term recurrence rates (Selles et al., 2018).
Limited fasciectomy
Limited fasciectomy excises the diseased tissue and is the most common treatment offered to DD patients (Van Rijssen et al., 2012). Recovery after the procedure takes around 6 weeks (Rodrigues et al., 2015). In a randomized control study comparing PNF and LF, LF patients experienced a greater statistically significant improvement in their total passive extension deficit after 6 weeks (Mendelaar et al., 2019). Complications include arterial damage (3.3–5%), nerve damage (2–3.8%), infection (2.4–9.6%) and tendon rupture (0.1%) (Denkler et al., 2022). Long-term complications include complex regional pain syndrome and a small risk of diffuse finger stiffness that can affect not only the operated finger but also other fingers of the hand. The recurrence rate after 5 years is 20.9% (Rodrigues et al., 2015).
Alser et al. (2020) showed that repeat LF surgery had a greatly increased risk of complications. The cumulative incidence of finger amputation after a primary LF was 0.3%, whereas the cumulative incidence of amputation after a secondary LF was 1.53% (Alser et al., 2020a).
Dermofasciectomy
Dermofasciectomy excises the affected DD fascia along with the overlying palmar skin; the resultant wound being resurfaced with a full thickness skin graft is thought to be more resistant to disease recurrence (Armstrong et al. 2000). This intervention is the most invasive and is associated with longer recovery times and increased risk of complications, such as skin graft failure, nerve injuries and infection (Dahlin et al., 2012; Denkler et al., 2022).
Comparison studies of surgical interventions
Limited fasciectomy vs. DF with a ‘firebreak’ skin graft: a prospective randomized trial by Ullah et al. (2009) trialled using DF with the addition of a ‘firebreak’ skin graft, proposed to prevent spreading of contracture across the tissues. However, a follow-up study after 3 years did not identify any significant improvements in recurrence or contracture correction.
Limited fasciectomy vs. PALF: A randomized control trial by Kan et al. (2016) showed that patients after PALF were able to return to daily activity more quickly than after LF. Both procedures had similar outcomes after 1 year. However, a follow-up study 5 years later established that the rates of recurrence with PALF were markedly worse (77% recurrence with PALF, compared with 32% recurrence with LF) (Selles et al., 2018). This highlights the importance of long-term monitoring of novel treatments.
Limited fasciectomy vs. PNF: A randomized clinical trial by Van Rijssen et al. (2012) showed recurrence after 5 years to be 84.9% in PNF, compared with 20.9% for limited fasciectomy. Additionally, recurrence after PNF was observed to begin earlier than after LF (Van Rijssen et al., 2012). The ongoing ‘Hand-2’ trial (ISRCTN12525655) looking into the clinical and cost-effectiveness of PNF vs. LF for treatment of Dupuytren’s contracture with postoperative follow-up of 2 years is scheduled to be completed in 2026 (Davis, 2024). It will provide further information about recurrence, patient-reported hand function and symptoms (Davis et al., 2020).
Salvage procedures
Proximal interphalangeal joint fusion or elective amputation at the PIPJ or proximal phalanx are possible salvage procedures for people with severe Dupuytren’s disease not amenable to any of the above procedures (Denkler et al., 2022). A retrospective cohort study by Bolt et al. (2021) reported long-term outcomes of 11 patients with severe recurrent DD who underwent PIPJ fusion. At a mean follow-up of 8 years and 9 months, no study participants required revision surgery. Overall, the patients reported a good quality of life after this procedure.
A study by Degreef and De Smet (2009) looked at data from a single secondary referral hand centre. Over 5 years, 12 of the 31 elective finger and ray amputations carried out at the centre were because of DD and 11 of them were because of recurrent DD and took place after a mean of 2.5 previous interventions.
Alser et al. (2020) showed that overall, the 90 day postoperative amputation rate was 0.55%. The 90 day amputation risk was low after primary surgery (0.3%) and higher after the first reoperation (1.5%). The 90 day risk rose markedly to 8% if the patient had undergone a LF after a previous DF. This may be owing to the scarring caused after previous extensive surgery, leading to an increased risk of arterial damage (Alser et al., 2020a).
A novel alternative to PIPJ fusion or amputation involving middle-phalanx excision and ligament construction has been described in two patients by Eiriksdottir and Atroshi (2019). The surgery created a shorter finger with a functioning joint that enabled finger flexion.
Future avenues of research
New studies have focused on identifying and targeting the molecular mechanisms that lead to disease progression. The main aim for treatment is to move away from surgical management and towards early-stage medical prevention strategies, a significant step-change in disease management. Overall, results have shown potential in vitro and in animal models and although human studies have been begun for some targets, the trials are yet to show full proof of the concept in humans (Nanchahal and Chan, 2023).
Anti-tumour necrosis factor (TNF) signalling has been shown to be an important pathway for DD progression (Verjee et al., 2013) and they showed that TNF, acting via the WNT signalling pathway, was necessary for fibroblast-to-myofibroblast transition. Collagen I contraction has also been shown to be dependent on local TNF production (Nanchahal et al., 2022). Dobie et al. (2022) observed the upregulation of TNF receptor TNFRSF12A in pathogenic cell populations. Inhibition of this receptor with polyclonal antibodies prevented the activation and proliferation of pathogenic myofibroblasts, identifying a potential pharmacological target for further investigation. Tumour necrosis factor therapy has subsequently progressed to human trials. Intranodular injections of adalimumab were tested for the treatment of early-stage DD in a randomized trial by Nanchahal et al. (2022). Preliminary results show that the therapy successfully reduced nodule size and hardness over 18 months of monitoring but the authors note that further long-term observation would be required to fully assess the efficacy of preventing surgery (Nanchahal et al., 2022).
Lambi et al. (2023) have focused on preventing fibrosis by targeting the downstream actions of TGF-β and to a lesser extent TNF, by inhibiting an extracellular signalling protein. Cell Communication Network Factor 2 (CCN2) is found in the ECM and is an essential mediator in TNF-β driven fibrosis. They suggested that inhibition of CCN2 via pamrevlumab, a monoclonal antibody inhibitor of CCN2, could be a possible method for slowing DD progression. Pamrevlumab has been used in vivo to successfully prevent and reverse fibrosis in rat musculoskeletal and dermal tissue fibrosis models. Although not tested directly in DD, the similarity in pathogenesis of the fibrogenic conditions indicates that CCN2 could be a viable therapeutic target for further study.
As well as increased collagen formation, atypical collagen maintenance in the hand has also been linked to the development of DD. Itoh et al. (2021) showed that myofibroblasts from DD patients carrying a variant in MMP14 had greatly impaired collagenolytic activity and a marked decrease in collagen breakdown. Compared with the wild-type enzyme, those with a homozygous variant had only 17% collagenolytic activity. Allosteric modulators of MMP14 may represent a future therapeutic option to restore collagen homeostasis.
A thorough understanding of the biology of DD is critical to future efforts to design treatments to prevent recurrence after surgery and perhaps the need for surgery in the first place.
Conclusion
Dupuytren’s disease is managed primarily via surgery, which carries a risk of complications and of recurrence. Repeat surgery carries increased risks and worse outcomes, whilst leaving an untreated affected hand can have a significant influence on quality of life. Currently, interventions are corrective procedures only. Even with an early diagnosis, we are unable to halt or reverse the progression of disease owing to lack of effective medical treatments. This highlights the relevance of the current intense research efforts that seek to understand the molecular biology and pathophysiology of the disease, particularly so that this knowledge can be used to identify therapeutic targets in the early stages of disease. Ideally, medical management would eventually eliminate the need for surgery but this is not yet feasible. In the meantime, ongoing clinical trials are aiming to optimize surgical decision making and outcomes.
Footnotes
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