Factors in the pathogenesis of Dupuytren's contracture

This article reviews the basic science elements involved in the pathogenesis of Dupuytren's disease. Dupuytren's contracture is effected by a multitude of complex processes at the cellular level and the exact relative contribution of each is unknown. Various investigators have proposed different theories and documented individual findings regarding the pathophysiology of Dupuytren's contracture. The current report attempts to summarize many of these findings together in a schema of pathogenesis.     

The collagen changes of Dupuytren's contracture

In Dupuytren's contracture there is an increase in the ratio of type III to type I collagen. The objective of this study was to determine if fibroblasts from patients with Dupuytren's contracture have an intrinsic aberration in collagen production or whether local factors govern the collagen changes in Dupuytren's contracture. Using a new collagen micro-method, we found that fibroblasts cultured from palmar fascia affected by Dupuytren's contracture produced similar collagen to fibroblasts derived from the palmar fascia of age- and sex-matched patients with carpal tunnel syndrome. Furthermore, the collagen changes of Dupuytren's contracture could be reproduced in all cell lines by increasing fibroblast density. At high fibroblast density, type I collagen production was inhibited: a finding that could account for the increased types III/I collagen ratio in Dupuytren's contracture. These results suggest that a genetic defect in collagen production is unlikely and that the important phenomenon is an increase in fibroblast density.     

Clinical aspects and surgical treatment of Dupuytren contracture

The etiology of Dupuytren's contracture is still not clear. Many theories have been proposed, but no basic data are currently available that would make it possible to treat Dupuytren's contracture by other methods than surgical intervention. The surgical technique used in our clinic is described, and a postoperative treatment is also outlined. This paper is designed to propose an acceptable technique for practicing trauma and hand surgeons.     

Dupuytren's contracture: morphological and biochemical changes in palmar aponeurosis

The palmar aponeurosis removed from ten patients with Dupuytren's contracture was studied using morphological and biochemical approaches. The histological characteristic of Dupuytren's contracture is the presence of numerous nodules among the lamellar structures of the collagen fibres. In the nodules, there are many active fibroblasts which are surrounded by immature fibres and metachromatic substances demonstrated by toluidine blue staining. Ultrastructurally, the active fibroblasts have the characteristics of myofibroblasts, as previously reported by Dr. Gabbiani. We found that some fibroblasts have intracellular collagen fibrils in the cytoplasm. When assayed by Siegel and Martin's method, lysyl oxidase activity of the palmar aponeurosis was significantly higher in Dupuytren's contracture than in normal hands. Biochemical studies such as electrophoretic analysis of mucopolysaccharides, determination of uronic acid and collagen contents were undertaken to compare the aponeurosis of Dupuytren's contracture with normal cases. The uronic acid contents were higher in Dupuytren's contracture than in the controls. However, no difference between the two groups was found in the collagen contents and in the composition of the mucopolysaccharides. These characteristic features; existence of myofibroblasts and intracellular collagen fibrils and increase in the activity of lysyl oxidase probably play a significant role in the establishment of flexion contracture of the fingers in Dupuytren's contracture.     

The Surgical Release of Dupuytren's Contracture Using Multiple Transverse Incisions

Dupuytren's contracture is a condition commonly encountered by hand surgeons, although it is rare in the Asian population. Various surgical procedures for Dupuytren's contracture have been reported, and the outcomes vary according to the treatment modalities. We report the treatment results of segmental fasciectomies with multiple transverse incisions for patients with Dupuytren's contracture. The cases of seven patients who underwent multiple segmental fasciectomies with multiple transverse incisions for Dupuytren's contracture from 2006 to 2011 were reviewed retrospectively. Multiple transverse incisions to the severe contracture sites were performed initially, and additional incisions to the metacarpophalangeal (MCP) joints, and the proximal interphalangeal (PIP) joints were performed if necessary. Segmental fasciectomies by removing the fibromatous nodules or cords between the incision lines were performed and the wound margins were approximated. The mean range of motion of the involved MCP joints and PIP joints was fully recovered. During the follow-up periods, there was no evidence of recurrence or progression of disease. Multiple transverse incisions for Dupuytren's contracture are technically challenging, and require a high skill level of hand surgeons. However, we achieved excellent correction of contractures with no associated complications. Therefore, segmental fasciectomies with multiple transverse incisions can be a good treatment option for Dupuytren's contracture.     

An investigation into the role of inflammatory cells in Dupuytren's disease

An immunohistochemical study was performed on nodules excised from the palmar fascia of patients with Dupuytren's contracture. In cellular nodules, antibodies to actin (used as a marker for myofibroblasts), desmin, vimentin, Mac 387 (a macrophage marker) and leucocyte common antigen were used. A correlation was demonstrated between the numbers of macrophages and the presence of myofibroblasts. The presence of myofibroblasts is generally considered to indicate the active stage of the disease. Inflammatory cells other than macrophages were largely absent from the nodules, although lymphocytes were frequent in the tissue around the nodules. Microvascular changes were prominent in the nodules and pericyte proliferation was observed around occluded capillaries. Release of growth factors from macrophages may be important in Dupuytren's contracture, as is the case in other fibrotic diseases. The possible role of macrophages in the aetiology of Dupuytren's disease is discussed.     

Gelatinase A activity in Dupuytren's disease

PURPOSE: Dupuytren's contracture is a fibroproliferative disorder of the hand characterized by an abnormal myofibroblast and fibroblast proliferation and extracellular matrix deposition leading to retraction and deformation of the palm. Recent studies have shown that molecules of extracellular matrix may coordinate morphogenesis, cell differentiation, and most importantly, fibrogenesis in tissue. Gelatinase A (MMP-2) is a member of the matrix metalloproteinase family of proteolytic enzymes that contribute to remodeling the extracellular matrix by degrading its components. The aim of this study was to determine the level of MMP-2 activation in the palmar fascia of patients with Dupuytren's contracture with reference to the clinical stages of disease progression and recurrence of the contracture after surgery. METHODS: The level of relative MMP-2 activation, expressed by the active to latent MMP-2 ratio, was investigated with use of zymography and computerized densitometry in 16 normal and 71 pathologic tissues characterizing different clinical stages of the disease progression. RESULTS: We found that the level of MMP-2 activation was significantly elevated in the palmar fascias with Dupuytren's contracture compared with normal tissues. We did not find statistically significant differences between groups with different stages of the disease progression. We also did not find a relation between a high level of MMP-2 activation and the recurrence in the area of surgically treated Dupuytren's contracture. CONCLUSIONS: The differences in MMP-2 activation between contractured and normal fascia suggest a participation of this enzyme in the promotion of Dupuytren's disease. We did not find a relationship, however, between the level of MMP-2 activation and the secondary contracture.     

Langerhans cells in Dupuytren's contracture

We have examined biopsies of Dupuytren's contracture palmar fascia, overlying subcutis and skin, and have correlated the distribution of gross macroscopic changes in the hand, mapped pre- and intraoperatively, with light microscopic immunohistochemical findings. We report increased numbers of S100 positive Langerhans cells (an epidermal cell of dendritic lineage) and CD45 positive cells, both in "nodules" and at dermo-epidermal junctions, in the biopsied tissues. This suggests that Langerhans cells migrate from the epidermis into Dupuytren's contracture tissue, possibly in response to local changes in levels of inflammatory cytokines within the tissue. Our findings, together with other reports of increased numbers of dermal dendrocytes and inflammatory cells in Dupuytren's contracture tissue, lend circumstantial support to the "extrinsic theory" of the pathogenesis of Dupuytren's contracture. However, the earliest stages of the disease process have not been defined, and therefore the events which ultimately produce fibrosis in the palmar fascial complex in susceptible individuals could begin in the skin and/or within deeper tissues, especially where there is dysregulation of the immune system.     

Clinical effectiveness of post-operative splinting after surgical release of Dupuytren's contracture: a systematic review

Background  

Splinting after contracture release for Dupuytren's disease of the hand is widely advocated. The purpose of this systematic review was to evaluate the quantity and quality of evidence regarding the effectiveness of splinting in the post-surgical management of Dupuytren's contractures.     

Dupuytren's contracture and sarcoma

In order to study possible connections between Dupuytren's contracture and sarcoma we analysed the records of 18 patients who developed sarcoma 5 years or more after surgery for Dupuytren's contracture. We found an increased frequency of fibrosarcoma and malignant fibrous histiocytoma, but these patients did not differ from the other patients in the study group. Our analysis suggests that neither smoking, diabetes nor cancer syndromes can explain why patients with Dupuytren's contracture have a higher incidence of sarcoma.     

Skin tension in the aetiology of Dupuytren's disease; a prospective trial

Tension in the palmar fascia has been proposed as a factor causing Dupuytren's disease. If tension does stimulate the growth of new Dupuytren's tissue, relieving longitudinal tension should reduce the recurrence rate following surgery. Thirty patients with palmar Dupuytren's contracture of a single ray that affected only the metacarpophalangeal joint were divided into two groups. Both groups had a fasciotomy: one group through a transverse incision that was closed directly and the other through a longitudinal incision with Z-plasty closure. Half the patients (seven of 14) who had direct closure had recurrence at 2 years as compared to two of the 13 in the Z-plasty group. The trial was stopped at the interim analysis stage due to the high recurrence rate in the first group. These results are consistent with the tension hypothesis for the aetiology of Dupuytren's disease.     

Androgen receptors in Dupuytren's contracture.

Palmar fascia tissue and cultured cells from patients with Dupuytren's contracture and from normal subjects were characterized and analyzed for androgen receptor expression. Androgen receptors have never been studied in Dupuytren's myofibroblasts and may have a role in its high male predominance. Surgical samples were collected from eight patients undergoing surgery for Dupuytren's contracture and from four patients with carpal tunnel syndrome, used as control tissue. Immunohistochemical analysis was performed on tissue samples and on cell cultures with anti-androgen receptor, anti-alpha-smooth muscle actin, anti-fibronectin, and anti-type I and III collagen antibodies using the biotin avidin peroxidase method as revelatory system. Immunostaining for androgen receptors in tissue samples and cultured cells revealed nuclear reaction in many Dupuytren's myofibroblasts, but in few fibroblasts of the normal palmar fascia. In a double-labeling study, androgen receptors were seen to co-localize with alpha-actin in both cell cultures and tissue samples. We present the first evidence that the palmar fascia is a target tissue for androgen action and that the expression of androgen receptors in Dupuytren's contracture is considerably higher than in the normal palmar fascia. Further studies will need to evaluate whether the androgen-responsive state of the tissue is related to the high incidence of Dupuytren's contracture in the male sex.     

The role of the fibroblast in Dupuytren's contracture.

Ultrastructural, immunohistochemical, and biochemical studies to date show that the fibroblast in Dupuytren's contracture is identical to palmar fascia fibroblasts in patients unaffected by Dupuytren's contracture, and to all other fibroblasts. The major difference relating to fibroblasts is that in Dupuytren's contracture there are more of them, and they are clustered around narrowed microvessels. It is probable that these two phenomena are linked because recent studies indicate a greater potential for ischemia-induced oxygen free radical generation in Dupuytren's contracture, and because oxygen free radicals in these concentrations can stimulate fibroblast proliferation. The major source of oxygen free radicals is likely to be from microvascular endothelial xanthine oxidase-catalyzed reactions. These observations also account for many of the epidemiologic associations of Dupuytren's contracture, because (1) age, race, and diabetes are associated with microvessel narrowing and (2) age, diabetes, alcohol consumption, HIV infection, cigarette smoking, and trauma are associated with increased free radical generation. Nonsteroidal anti-inflammatory drugs and allopurinol are two agents that decrease oxygen free radical release and may inhibit or prevent Dupuytren's contracture.     

Dupuytren's contracture: a retrospective database analysis to assess clinical management and costs in England

Background  

Dupuytren's disease is a fibro-proliferative disorder affecting ~3-5% of the UK population. Current surgical treatments for Dupuytren's contracture (DC) include fasciectomy and fasciotomy. We assessed the clinical management of DC in England over a 5-year period; associated NHS costs were assessed for a 1-year period.     

An accessory superficialis tendon involved by Dupuytren's contracture

A 60-year-old Caucasian male presented with Dupuytren's contracture affecting his left little finger. On exploration he was found to have a band of Dupuytren's tissue attached to an accessory superficialis tendon.     

Cigarette smoking and Dupuytren's contracture of the hand

Microvascular occlusion has been implicated as a possible causative factor of Dupuytren's contracture. Cigarette smoking is one of the most significant factors in the development of peripheral vasculopathy. The relationship between smoking and Dupuytren's contracture of the hand is explored in this article. One hundred thirty-two consecutive patients who had a partial fasciectomy for treatment of Dupuytren's contracture from 1980 to 1985, were analyzed retrospectively. There were 111 males and 21 females. Ninety (68.2%) of 132 patients smoked cigarettes compared with 110 (37.2%) of 296 randomized hospitalized control patients (p less than 0.00001). Eighty (72.1%) of 111 men smoked cigarettes compared with 65 (44.2%) of 147 male control patients (p = 0.000015). Cigarette smoking is linked statistically to Dupuytren's disease and may be involved in its pathogenesis by producing microvascular occlusion and subsequent fibrosis and contracture or by some other mechanism.     

A retrospective review of the management of Dupuytren's nodules

PURPOSE: To evaluate the progression of Depuytren's nodules with more than 6 years of follow-up study. METHODS: Fifty-nine patients who presented initially with Dupuytren's nodules returned for physical examination at an average follow-up period of 8.7 years (range, 6-15 y). Patients were questioned regarding family history of Dupuytren's disease, family ethnicity, alcohol consumption, smoking, liver disease, seizures, diabetes, and signs of systemic disease such as knuckle pads and plantar nodules. Physical examination evaluated disease state, loss of extension of the finger joints, and disease location. RESULTS: Thirty of the 59 patients with previously diagnosed isolated nodules developed a cord. Twenty-two percent of patients presented with bilateral disease and another 26% developed bilateral disease. Of those patients whose disease progressed 43% had European heritage, 37% had disease onset before the age of 50 years, 30% had bilateral disease, 23% had a family history of Dupuytren's disease, and 13% had plantar nodules. Five patients lost extension averaging 60 degrees at the metacarpophalangeal joint and 40 degrees at the proximal interphalangeal joint. Three of these 5 had surgical excision because they had a flexion contracture of the metacarpophalangeal or proximal interphalangeal joints averaging 60 degrees and 43 degrees , respectively. Another 7 patients did not meet standard criteria but had surgery for persistent pain associated with grasping objects (without contracture). All surgically treated patients had at least 1 risk factor and 7 patients had more than 1 risk factor. In 7 patients the Dupuytren's nodule had resolved at the time of follow-up evaluation. CONCLUSIONS: The progression of the nodular form of Dupuytren's disease to cord-like disease is common but not inevitable. This evaluation of Dupuytren's nodules has shown that at an average of 8.7 years after diagnosis 5 patients met standard surgical criteria of metacarpophalangeal contracture of greater than 30 degrees or any proximal interphalangeal contracture. Age of onset (before 50 years) is correlated most closely with disease progression, and the disease regressed in 7 patients (12%).     

Some medicolegal aspects of Dupuytren's contracture.

This article presents the medical and legal aspects of Dupuytren's contracture. It also presents a rational basis for the assessment of the relationship, if any, between a patient's occupation and the development of Dupuytren's contracture.     

Enzymes of glucose metabolism in palmar fascia and Dupuytren's contracture.

Several enzymes participating in glucose metabolism and some of the acid hydrolases were assayed in palmar fascia and Dupuytren's contracture with fluorometric microanalytical methods. The enzyme activities of glucose metabolism were lower in normal palmar fascia than in dermis. The fascia of Dupuytren's contracture exhibited a general increase in the enzyme activities of glucose catabolism. Little alteration was found in alanine aminotransferase and UDP-glucose dehydrogenase activity in the lesion. Lysosomal hydrolytic enzyme activities were increased five to ten times in Dupuytren's tissue. The dermis overlying Dupuytren's contracture exhibited an increase in the enzyme activities of glucose catabolism, but to a lesser degree than did the fascia of the lesion. The epidermis of involved palmar skin displayed normal enzyme activities.