Connective Tissue Degeneration Mechanisms of Palm

Authors: S Karkampouna M Kreulen M C Obdeijn P Kloen A L Dorjée F Rivellese A Chojnowski I Clark Marianna Kruithofde Julio

Publish Date: 2016/07/14

Volume: 2, Issue: 3, Pages: 133-140

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Abstract

Dupuytren’s disease is a connective tissue disorder of the hand causing excessive palmar fascial fibrosis with associated finger contracture and disability The aetiology of the disease is heterogeneous with both genetic and environmental components The connective tissue is abnormally infiltrated by myofibroblasts that deposit collagen and other extracellular matrix proteins We describe the clinical profile of Dupuytren’s disease along with current therapeutic schemes Recent findings on molecular and cellular parameters that are dysregulated in Dupuytren’s disease which may contribute to the onset of the disease and the role of resident inflammation promoting fibrosis are highlighted We review recent literature focusing on nonmyofibroblast cell types stem celllike cells their proinflammatory and profibrotic role that may account for abnormal wound healing responseWound repair and tissue regeneration after injury is widely accepted to occur during the adult life of large mammals In humans liver regeneration after partial hepatectomy 1 or gum regeneration 2 is a complete and restorative process However skin wounds incisions or excisions lead to formation of scar tissue which does not resolve for a long term thus the cellmediated tissue regeneration is incomplete while scar tissue persists Embryonic skin wounds lead to scarfree completely regenerated tissues while the majority of mechanical injuries during adult life lead to scar tissue formation 3 Thus there might exist a “codependent” link between tissue regeneration cell replenishment and scarring The early phases of the wound healing response are dependent on inflammation and fibrogenesis recruitment of platelets immune cell and fibroblast invasion proinflammatory cytokine secretion differentiation of fibroblasts to myofibroblasts and fibrin clot formation If the damaging stimuli are repetitive this will lead to persistent inflammation higher levels of interleukins tumor necrosis factor alpha TNFα and profibrogenic transforming growth factor beta TGFβ and therefore scarring It has been proposed that the same signals that regulate scarfree embryonic regeneration also regulate the adult wound healing response These cellular processes might be controlled by the levels and/or localization of those same signals as well as of the extracellular context developmental stage tissue specificity and repetitive versus acute injuryIn the case of Dupuytren’s disease DD although it is not clear whether its pathogenesis is of mechanical or biochemical nature the net result is the same excess production of matrix proteins and excessive accumulation of extracellular matrix scarring which changes tissue architecture and causes digital contraction Perhaps we should reevaluate DD not only as excess scarring but also as a condition of abnormal tissue regenerationa Clinical presentation of Dupuytren’s disease preoperative rigid contracture surgical incision during palmar fasciectomy with prevalent collagen cord resected nodule and cord specimen b Immune cell types leukocytes monocytes B and T cells residing in nodules from DD patient material FACS analysis N = 3 c Immunofluorescence of CD3 alpha smooth muscle actin αSMA tryptase and CD68 expression in Dupuytren’s nodules DAPI nuclei d Ex vivo culture of Dupuytren’s nodules and treatments with mast cell stabilizer chromolyn Immunofluorescence for αSMA myofibroblasts and tryptase expression mast cells e Ex vivo culture of Dupuytren’s nodules and treatment with antiTNFa antibody golimumab and control IgG Immunofluorescence for αSMA myofibroblasts and CD68 expression macrophagesDisease progression leads to longitudinally oriented cordlike structures that limit extension of the involved fingers and ultimately to metacarpophalangeal MCP and interphalangeal joint PIP or DIP contractures 5 Younger patients often have a more aggressive disease progression Most patients with a first presentation of DD do not have pain or functional disability and require no treatment A small extension deficit of the MCP joints might lead to a positive “tabletop test” the hand cannot lie flat on a tabletop but few patients experience functional limitations The indications for treatment are governed by functional loss and progression and may be subject to local healthcare system guidelines An extension deficit greater than 30° may lead to contracture of the accessory collateral ligaments and the palmar plate of the PIP joint PIP joint contractures are generally regarded as more difficult to treat than MCP contractures because of the secondary joint contracture and weakening of the extensor mechanism caused by palmar fibrosisA wide range of treatment options are available 6 generally involving mechanical release or excision of excessive fibrotic tissue However recurrence rates are high ranging from 8 to 66  average 33  7 The surgeon and patient should be aware that there is no curative treatment for the disease

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