A systematic review and meta-analysis on the prevalence of Dupuytren disease in the general population of Western countries

Abstract

Background: Dupuytren disease is a fibroproliferative disease of palmar fascia of the hand. Its prevalence has been the subject of several reviews; however, an accurate description of the prevalence range in the general population--and of the relation between age and disease--is lacking.

Methods: Embase and PubMed were searched using database-specific Medical Subject Headings; titles and abstracts were searched for the words "Dupuytren," "incidence," and "prevalence." Two reviewers independently assessed the articles using inclusion and exclusion criteria, and rated the included studies with a quality assessment instrument. In a meta-analysis, the median prevalence, as a function of age by sex, was estimated, accompanied by 95 percent prediction intervals. The observed heterogeneity in prevalence was investigated with respect to study quality and geographic location.

Results: Twenty-three of 199 unique identified articles were included. The number of participants ranged from 37 to 97,537, and age ranged from 18 to 100 years. Prevalence varied from 0.6 to 31.6 percent. The quality of studies differed but could not explain the heterogeneity among studies. Mean prevalence was estimated as 12, 21, and 29 percent at ages 55, 65, and 75 years, respectively, based on the relation between age and prevalence determined from 10 studies.

Conclusions: The authors describe a prevalence range of Dupuytren disease in the general population of Western countries. The relation between age and prevalence of Dupuytren disease is given according to sex, including 95 percent prediction intervals. It is possible to determine disease prevalence at a certain age for the total population, and for men and women separately.

Fig. 72.1

Types of cells derived as a result of chemical (polyethylene glycol/dimethyl sulfoxide - PEG/DMSO) ex vivo fusion of two different cell lineages. Fusion of cells derived from the same lineages creates syncytium with multiple nuclei N ≥ 2 (1) or with single nucleus – homotypic synkaryon (2). Fusion of cells derived from different lineages creates heterotypic synkaryon (3) or heterokaryon (4). If the fusion of cells derived from different lineages is not complete, hemi-fused cells are created (5). Toxicity of fusion can cause cell death (6). Cells can also not undergo fusion due to lack of other cells in proximity or inappropriate fusion conditions (7)

Fig. 72.2

The mechanism of polyethylene glycol/dimethyl sulfoxide (PEG/DMSO) induced donor-recipient chimeric cells creation via ex vivo cell fusion (CF). PEG mediated CF is a three-step process requiring the following: (1) aggregation or “close” (the intercellular distance may vary for different cells and fusion models) approach of membrane lipid bilayers due to hydrophobic properties of PEG that causes membrane dehydration; (2) removal of the water between adjacent cells; (3) the intermediate membrane destabilization (facilitated by PEG) is followed by creation of pores (facilitated by DMSO) in the membranes of cells undergoing fusion; (4) positive osmotic pressure created by PEG improves stabilization of fusion intermediates and leads to expansion of the pores, cell swelling and cell-to-cell fusion. The products of PEG/DMSO solution induced cell fusion may include (5) heterokaryon and synkaryon cells as well as cells that did not undergo fusion process. More detailed descriptions of cell fusion mechanism can be found in articles by Lentz [62, 63]

Fig. 72.3

Experimental model of ex vivo creation of the donor-recipient chimeric cells (DRCC). DRCC will be created ex vivo by the chemical polyethylene glycol (PEG) induced cell fusion of the bone marrow cells harvested from the ACI (RT1^a) and Lewis (RT1^l) rat donors. Isolated bone marrow cells will be separately stained with two different (red/orange and green) fluorescent dyes. Next, the ex vivo fusion will be performed using PEG. Supportive therapy using the fused DRCC will be given based on the double fluorescent staining and will be injected into the bone of Lewis (RT1^l) rat recipients along with the donor matching (ACI) VCA (skin allograft) transplant. * – Seven day protocol of combined αβ-TCR mAb (250 μg/day) and CsA (16 mg/kg/day) therapy

Fig. 72.4

Future applications of the ex vivo created donor-recipient chimeric cells used as supportive therapy in the clinical scenario. Human donor-recipient chimeric cells can be utilized as a supportive therapy for solid organ (living donor- kidney, liver transplantation) and in the future for vascularized composite allotransplantation (VCA). Progenitor cells derived from sources such as bone marrow or cord blood will be isolated, fluorescently labeled using two different cell membrane dyes (PKH26 and PKH67), and will be fused ex vivo using PEG technique creating the donor-recipient chimeric cells. Based on the double fluorescent staining, the ex vivo fused chimeric cells will be sorted out and delivered via either the intraosseous or intravenous route to the recipient at the day of solid organ or VCA transplants. Panel (a) – Patients receiving transplant from the living donor will be supported with the bone marrow derived donor-recipient chimeric cells collected from both the donor and the transplant recipient. Panel (b) – If access to the donor and/or recipients bone marrow cells is not possible (i.e. recipient is suffering from severe bone marrow deficiencies due to gamma irradiation or organ donor deceased), the donor and recipient HLA-matched cord blood cells can be used to create an ex vivo donor-recipient chimeric cells and to apply them as a supportive therapy