Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration (Dupuytren’s Disease)

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 non-myofibroblast cell types (stem cell-like cells), their pro-inflammatory and pro-fibrotic role that may account for abnormal wound healing response.

Verteporfin ameliorates fibrotic aspects of Dupuytren’s disease nodular fibroblasts irrespective the activation state of the cells

“…DD is a chronic, fibroproliferative disorder of the hand fascia, which results in impairment of the extension of fingers and therefore hinders a normal use of the hand. Treatments for DD in early stages unfortunately show lack of effectiveness, while the management of the final stage is invasive and often results in disease recurrence 15 . Therefore, the need for a treatment that at least prevents the progression of the disease is high.…”

“…The late stage contractures are treated by surgical interventions such as fasciotomy, fasciectomy or dermofasciectomy and skin grafting 1 , 2 , 6 , 7 , 13 , 14 . However, all of the above interventions frequently lead to recurrences 15 – 17 . Unfortunately, as is the case with fibrosis in general, an effective pharmacological treatment has not been developed yet.…”

Clinical Insights into the Importance of Scars and Scar Release in Paediatric Chronic Myofascial Pain

“…If the healing process is interrupted by tissue disruption, infection or a comorbid disease process, then a pathological scar may occur, which may be atrophic, hypertrophic, tethered, or keloid in nature. Development of pathological scars may be related to genetics, as well as differences in the duration, and intensity of the inflammatory process in the reticular dermis [56,[59][60][61]. Excessive scar tissue movement, scar rubbing, scar scratching or abnormal tension related to surgery or injury may also induce an enhanced neurogenic inflammatory response [18,[62][63][64][65].…”

Basic science approaches to common hand surgery problems

“…One of the most vexing and researched conditions related to fibrosis in the hand is Dupuytren's disease. Immune cells, including monocytes macrophages and T cells, can be seen in abundance in Dupuytren's disease and suggest some inflammatory effectors of this process (Karkampouna et al, 2016). However, recent genomic-wide analysis of human Dupuytren's samples suggest decreased WNT pathway antagonist secreted frizzled-related protein (SFRP) 4 may be a common mutation in developing Dupuytren's, implicating the WNT pathway role in promoting fibrosis within the fascia (Ng et al, 2017).…”