Eighteen years follow-up study of the clinical manifestations and progression of Dupuytren's disease

Guðmundsson, Kristján G.; Arngrı́msson, Reynir; Jónsson, Þorbjörn

doi:10.1080/030097401750065292

Cited by 55 publications

(18 citation statements)

References 14 publications

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“…Dupuytren’s disease (DD) is extremely common and is estimated to affect approximately 4% of the general UK and US populations 1 . Between 35–50% of patients with early DD manifest as nodules on the palmar aspect of the hand go on to develop finger contractures 2 , 3 . The nodules are typically quiescent for a period and then become active, progressing to flexion deformities over a period of months 4 .…”

Section: Introductionmentioning

confidence: 99%

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with an embedded dose response study.

Nanchahal¹,

Ball²,

Swettenham³

et al. 2017

Wellcome Open Res

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Dupuytren’s disease is a common fibrotic condition of the hand affecting 4% of the population and causes the fingers to curl irreversibly into the palm. It has a strong familial tendency, there is no approved treatment for early stage disease, and patients with established digital contractures are most commonly treated by surgery. This is associated with prolonged recovery, and less invasive techniques have high recurrence rates. The myofibroblasts, the cells responsible for the excessive matrix deposition and contraction, are aggregated in nodules. Using excised diseased and control human tissue, we found that immune cells interspersed amongst the myofibroblasts secrete cytokines. Of these, only tumour necrosis factor (TNF) promoted the development of myofibroblasts. The clinically approved anti-TNF agents led to inhibition of the myofibroblast phenotype in vitro. This clinical trial is designed to assess the efficacy of the anti-TNF agent adalimumab on participants with early disease. The first part is a dose-ranging study where nodules of participants already scheduled for surgery will be injected with either placebo (saline) or varying doses of adalimumab. The excised tissue will then be analysed for markers of myofibroblast activity. The second part of the study will recruit participants with early stage disease. They will be randomised 1: 1 to receive either adalimumab or placebo at 3 month intervals over 1 year and will then be followed for a further 6 months. Outcome measures will include nodule hardness, size and disease progression. The trial will also determine the cost-effectiveness of adalimumb treatment for this group of participants.

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Section: Introductionmentioning

confidence: 99%

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with an embedded dose response study.

Nanchahal¹,

Ball²,

Swettenham³

et al. 2017

Wellcome Open Res

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“…However they all suffer from disadvantages. The ideal would be a treatment that prevents progression in the 30–50 % [ 5 , 6 ] of at risk patients with early DD. A variety of treatments have been proposed for early DD but there is currently no clear evidence for their role and efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…However, it may be difficult to ascribe nodule resolution to treatment as nodules have been reported to regress spontaneously. An epidemiological study conducted in Iceland reported that of 56 men initially noted to have nodules or cords, 8 were judged to have normal hands 18 years later [ 5 ]. The variation in diagnostic criteria for DD has been noted [ 3 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

“…This is followed by a final stage as the cords mature and irreversible digital contractures develop, resulting in significant impairment of hand function [ 4 ]. However disease progression is not inevitable, with only 30-50 % going on to develop progressive flexion deformities [ 5 , 6 ] and that the course of DD may fluctuate over time [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Systematic review of non-surgical treatments for early Dupuytren’s disease

Ball

Izadi

Verjee

et al. 2016

BMC Musculoskelet Disord

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BackgroundDupuytren’s disease is a common fibrotic disorder of the palm characterized by the development of progressive flexion deformities in the digits, leading to significant functional impairment. Surgical excision remains the most common treatment. However, this is only indicated in patients with established contractures rather than those with early disease. Early disease is generally characterized by the presence of palmar nodules with limited or no contracture of the fingers. The ideal treatment would be directed at patients with early progressive disease to prevent future deterioration. Various non-surgical treatment modalities have been described but there is currently no systematic assessment of the role and efficacy of these treatments in patients with early disease.MethodsUsing a PICOS analysis we reviewed publications of studies of patients with early disease who had received physical therapies, pharmacological treatment, or radiotherapy. Following PRISMA guidelines titles and abstract were screened using predefined criteria to identify those reporting outcomes specifically relating to the treatment of early disease. In the absence of a definition of early disease studies were included if early DD was described clinically, with digital contractures not exceeding 30°, Tubiana grades N to 1, and which reported identifiable data. Studies were excluded if data for early DD patients could not be extracted for analysis.ResultsIn this systematic review, 26 studies were identified and analyzed to evaluate the effect of pharmacological therapy (n = 11), physical therapy (n = 5) and radiotherapy (n = 10) on early Dupuytren’s disease. The studies comprised 20 case series, 1 cohort study with the remainder reporting case studies. All publications were graded level of evidence 4 or 5 assessed using the Oxford Centre for Evidence Based Medicine grading. Narrative descriptions of the data are presented.ConclusionsPhysical therapies were the most robustly assessed, using objective measures but the studies were under powered, providing insufficient evidence of efficacy. Intralesional steroid injection and radiotherapy appeared to lead to softening of nodules and to retard disease progression but lacked rigorous evaluation and studies were poorly designed. There is an urgent need for adequately powered double blinded randomized trials for this common disorder which affects 4 % of the population.Trial registrationThe protocol was registered (CRD42015008986 16 November 2015) with the PROSPERO international prospective register of systematic reviews.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1200-y) contains supplementary material, which is available to authorized users.

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“…Between 35–50% of patients with early DD manifest as nodules on the palmar aspect of the hand go on to develop finger contractures 2, 3 . The nodules are typically quiescent for a period and then become active, progressing to flexion deformities over a period of months 4 .…”

Section: Introductionmentioning

confidence: 99%

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with an embedded dose response study.

et al. 2017

View full text Add to dashboard Cite

Dupuytren's disease is a common fibrotic condition of the hand affecting 4% of the population and causes the fingers to curl irreversibly into the palm. It has a strong familial tendency, there is no approved treatment for early stage disease, and patients with established digital contractures are most commonly treated by surgery. This is associated with prolonged recovery, and less invasive techniques have high recurrence rates.The myofibroblasts, the cells responsible for the excessive matrix deposition and contraction, are aggregated in nodules. Using excised diseased and control human tissue, we found that immune cells interspersed amongst the myofibroblasts secrete cytokines. Of these, only tumour necrosis factor (TNF) promoted the development of myofibroblasts. The clinically approved anti-TNF agents led to inhibition of the myofibroblast phenotype . This clinical trial is designed to in vitro assess the efficacy of the anti-TNF agent adalimumab on participants with early disease. The first part is a dose-ranging study where nodules of participants already scheduled for surgery will be injected with either placebo (saline) or varying doses of adalimumab. The excised tissue will then be analysed for markers of myofibroblast activity.The second part of the study will recruit participants with early stage disease. They will be randomised 1: 1 to receive either adalimumab or placebo at 3 month intervals over 1 year and will then be followed for a further 6 months. Outcome measures will include nodule hardness, size and disease progression. The trial will also determine the cost-effectiveness of adalimumb treatment for this group of participants.

show abstract

Eighteen years follow-up study of the clinical manifestations and progression of Dupuytren's disease

Abstract: The incidence of Dupuytren's disease is high in elderly men. Dupuytren's disease is progressive in nature and most operated patients have recurrent finger contractures.

Cited by 55 publications

References 14 publications

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with an embedded dose response study.

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with an embedded dose response study.

Systematic review of non-surgical treatments for early Dupuytren’s disease

Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with an embedded dose response study.

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