Systematic review of non-surgical treatments for early dupuytren's disease.

BACKGROUND: Dupuytren'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. METHODS: Using 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. RESULTS: In 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. CONCLUSIONS: Physical 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 REGISTRATION: The protocol was registered ( CRD42015008986 16 November 2015) with the PROSPERO international prospective register of systematic reviews.

Post-transcriptional regulation of alpha-smooth muscle actin determines the contractile phenotype of Dupuytren's nodular cells.

The objective was to study Dupuytren's myofibroblast cells in constrained collagen matrices in order to more closely emulate their in vivo environment and, to correlate their contractility with alpha-smooth muscle actin (alpha-SMA) expression and determine if dermal fibroblasts regulate Dupuytren's myofibroblast phenotype. Isotonic and isometric force contraction by cells isolated from Dupuytren's nodules, palmar and non-palmar skin fibroblasts was measured in collagen matrices. The effect of co-culturing nodule cells with dermal fibroblasts on isometric contraction was examined. Isometric contraction was correlated with levels of alpha-SMA mRNA by pcr and protein by Western blotting, and alpha-SMA distribution assessed by immunofluorescence. Dupuytren's nodule cells exhibited similar levels of isotonic contraction to both palmar and non-palmar dermal fibroblasts. However, nodule cells generated high levels of isometric force (mean: 3.5 dynes/h), which continued to increase over 24 h to a maximum of 173 dynes. In contrast, dermal fibroblasts initially exhibited low levels of contraction (mean: 0.5 dynes/h) and reached tensional homeostasis on average after 15 h (range: 4-20 h), with a maximum force of 52 dynes. Although all three cell types had similar alpha-SMA mRNA levels, increased levels of alpha-SMA protein were observed in nodule cells compared to dermal fibroblasts. alpha-SMA localised to stress fibres in 35% (range: 26-50%) of nodule cells compared to only 3% (range:0-6%) of dermal fibroblasts. Co-cultures of Dupuytren's cells and dermal fibroblasts showed no contractile differences. The contractile phenotype of Dupuytren's myofibroblasts is determined by increased alpha-SMA protein distributed in stress fibres, not by cellular mRNA levels. Dupuytren's cell contractility is not influenced by dermal fibroblasts.

Rotation in the interphalangeal thumb joint in vivo.

PURPOSE: To investigate rotation at the thumb interphalangeal (IP) joint in vivo to optimize the position of fusion of this joint. METHODS: Standardized photographs were taken of 176 thumbs end-on (88 asymptomatic volunteers) placed on a custom-made splint with the IP joint at 40 degrees . Three blinded investigators measured rotation at the IP joint from these photographs as the angle between a line aligning the eponychial folds and a line aligning the proximal phalanx condyles. Gender, age, hand dominance, and type of occupation of the asymptomatic vounteers were recorded. RESULTS: The variable pronation at the IP joint of the thumb (range, 0 degrees to 12 degrees) was significantly greater on the left than right (p=.001), although the actual difference was only 1 degrees . In subjects who performed fine dexterous work, thumb IP joint pronation was significantly less than in subjects who performed administrative or manual work (p=.009), but we found no statistical difference between manual and administrative groups. There was no correlation between thumb IP joint rotation and hand dominance (p=.2), age (p=.4) or gender (p=.5). CONCLUSIONS: There is functional pronation at the IP joint of the thumb. We propose that this should be taken into account when performing arthrodesis on the joint or designing a joint replacement. The degree of rotation may be associated with occupation.

Myofibroblast distribution in Dupuytren's cords: correlation with digital contracture.

PURPOSE: Dupuytren's tissue has typically been described as being composed of myofibroblast-rich palmar nodules and relatively acellular tendon-like cords. We aimed to determine myofibroblast distribution (alpha-smooth muscle actin [alpha-SMA] positive cells) within Dupuytren's tissue and to correlate histologically defined alpha-SMA-positive nodules with digital contracture and recurrent disease. METHODS: One hundred and three digital Dupuytren's cords (72 fasciectomy, 31 dermofasciectomy) were stained with anti-alpha-SMA antibody. The presence of alpha-SMA-positive nodules, their surface area, and alpha-SMA-positive cells were quantified throughout excised Dupuytren's tissue. Clinical data on diathesis, flexion deformity, and previous surgeries were collected. RESULTS: Cords were nodular (66%) or non-nodular (34%). Nodular cords contained 1 (55%), 2 (33%), or 3 or more nodules (12%) composed of localized collections of cells. The mean total nodule surface area was 23 mm(2) (range, 1.3-105 mm(2)). Nodules contained the highest number of alpha-SMA-positive cells (mean 97%, 2374 cells/mm(2)) compared to peri-nodular areas (mean 32%, 763 cells/mm(2)), and more distant cord (mean 8%, 495 cells/mm(2)). Non-nodular cords contained 9% to 17% alpha-SMA-positive cells (mean 475-663 cells/mm(2)), with higher numbers distally. There was greater digital contracture in patients with non-nodular cords. Thirty-six of 38 proximal interphalangeal (PIP) joint-marked samples had a nodule that co-localized with the PIP joint. Nodule size did not correlate with flexion deformity or with primary or recurrent disease. CONCLUSIONS: We found that two thirds of digital cords were nodular. Nodules were hypercellular, the majority being alpha-SMA-positive cells. Nodules varied in size and co-localized with the PIP joint. Cord was relatively cellular throughout; a proportion of these cells were alpha-SMA-positive and cells aligned with collagen fibers. Non-nodular cords correlated with significantly greater digital flexion contracture. We propose that cells in nodular cords contract and deposit extracellular matrix components. The matrix is then remodeled in shortened configuration, and as fixed flexion deformity develops, stress shielding eventually leads to myofibroblast apoptosis, and cord becomes less cellular.

Cutaneous endometriosis: a plastic surgery perspective.

Cutaneous endometriosis is a rare skin pathology that may present to the gynaecologist, general surgeon, dermatologist, or plastic surgeon. It is often misdiagnosed due to its rarity and variable appearance. In the current literature recommendations for its management vary greatly. We present a case of cutaneous endometriosis presenting to a plastic surgery service, as well as a review of the literature. Cutaneous endometriosis should be considered as a differential in any female presenting with an umbilical lesion, and should be diagnosed histiologically following an excision biopsy with 2 mm margins.