However, as the studies of McGrouther (1985) and McFarlane (1974, 1985b) have shown, the distribution of the lesions in Dupuytren's disease is not random but on the contrary follows the anatomical structures of the palmar and digital fascia. It could thus be possible that Dupuytren's disease arises not as pathological disorder but rather as the consequence of normal adaptive responses to applied stimuli to one or the other part of the fascia (Flint, 1990).
The analysis of the histological, biochemical and metabolical mechanism brought into play in the development of the disease shows indeed that most of them are non specific responses common to the different forms of connective tissue (Flint, 1990).
Examination of the organisation of the fibre bundles by the scanning electron microscope reveals significant changes in the general architecture of the collagen bundles compared to the normal fascia (Legge et al., 1981). Yet the aspect of individual fibres is normal.
Using indirect immunofluorescence, it is possible to determine the distribution of the various collagen types in tissues. When the normal aponeurosis is stained with antibodies to type I collagen, uniform staining occurs as expected (Bailey, 1993). With type III and V, the staining is limited to the periphery of the regularly arranged bundles. The nodules are intensely stained with antibodies to types III and V fibres, which are both randomly distributed amongst the major type I fibres, and the bundles are grossly disorganised. The fibrous bands reveal aligned fibres which stain for both type I and type III, but the type III fibres are randomly distributed rather than confined to the bundle sheaths as observed in the normal aponeurosis. Staining of the apparently unaffected areas reveals much of the same picture as for the normal aponeurosis, except that in some areas the staining of the bundle sheath is more intense. This clearly suggest that it is at the higher level of order of the fibre bundles or fascicles that the structure has broken down rather than at the level of the individual fibres themselves.
Murrell et al. (1989, 1991) have suggested that the change in the type I to III ratio is due to a decrease in the synthesis of type I collagen. This is unlikely because the decrease in type I necessary to account for the apparent increase in type III would be dramatic and improbable in fibrotic conditions (Bailey 1993).
The same changes in the proportions of the different types of collagen are observed in hypertrophic scars and granulation tissues. One would expect the greatest amount of type III in the nodules, where there is a rapid proliferation of collagen, and decreasing amounts in the bands as they mature, if Dupuytren's contracture follows the pattern of normal wounds and fibrotic lesions. However, a large amount of type III would be retained over a long period of time if the bands follow a similar course to those of the hypertrophic scar. Cross-link studies show that Dupuytren's disease bands do not mature (Bailey 1993), indicating more rapid turnover of collagen in the band. In addition, analysis of collagen from patients with long-standing Dupuytren's reveals biochemical changes similar to those in short-term disease (Brinkley-Parson et al. 1981), indicating a failure to mature analogous to what occurs in hypertrophic scars.
The major biochemical features of Dupuytren's disease are similar to those of hypertrophic scar tissue in that the tissue fails to mature as in normal scars but, instead, maintains a high turnover rate.
The ultrastructure studies have demonstrated that the collagen fibres themselves are normal, but it is at the higher level of the fibre bundle structure of the aponeurosis that irreversible damage is seen.
| Tissue | Glycosaminoglycans | Hyaluronic acid | Dermatan-sulfate | Chondroïtine-sulfate |
| Normal fascia | 100 | 100 | 100 | 100 |
| Active cord | 398 | 84 | 482 | 1164 |
| Nodule | 334 | 93 | 404 | 905 |
| Fibrous band | 200 | 68 | 257 | 449 |
These changes in the absolute level and in the proportions of the glycosaminoglycans are reflected in the spatial architecture of the extracellular matrix. Studies by Brandes et al. (1993) have shown that in the normal palmar fascia, the fibroblasts are embedded in an extracellular matrix containing parallel bundles of collagen fibrils with a diameter between 50 and 80 nm connected to each other by 3-4 nm thick, short, filaments of proteoglycans. These are orthogonally oriented along the fibrils at distances of 10-25 nm. In addition, long branched filaments with a similar thickness and a length of about 100 nm lay mainly parallel to the collagen fibrils and form a network in the broader interfibrillar spaces. In the nodules of Dupuytren's disease, the cells are surrounded by a tight network of 2-3 nm thick and about 100 nm long branched filaments. They bind at distances of 10-25 nm to collagen fibrils, about 40-60 nm thick. At greater distances from the cells, the collagen fibrils are very irregularly oriented abruptly changing their course but packed closer together than in the pericellular matrix.
The shorter filaments connected to the collagen fibrils could be composed of dermatan sulfate proteoglycans since they are present in normal and diseased fascia. The tight network of long branched filaments predominantly seen in the nodules around the myofibroblasts could contain most of the chondroitin sulfate. The small dermatan sulfate proteoglycans seem to have an important role in the fibrillogenesis and the alignment of newly formed collagen fibrils. In comparison, the large chondroitin sulfate proteoglycans of the hyaline cartilage and of Dupuytren's nodules fill the broad interfibrillar spaces and are typically found with small, randomy oriented collagen fibrils. These macromolecules are responsible of the resilience of the tissue: acting pressure forces the water between the glycosaminoglycan chains to be squeezed out and the fibrillar constituents to be stretched. Since after unloading the proteoglycans can again bind water, the tissue recovers to its previous state.
This also shows that the tissues involved in Dupuytren's disease retain their ability to adapt to acting forces.
In Dupuytren's disease, four types of connective tissue responses occur, sequentially or simultaneously:
The thickening of the palmar aponeurosis can be compared to the thickening and increase deposition of collagen observed in tendons as a response to increased loading (Carlstedt 1987).
The studies of Flint (1990) suggest that the modifications observed in the nodules are similar histologically and biochemically to those seen in partial intratendinous ruptures of the long head of the biceps for example. The intratendinous rupture leads to the development of nodular formations within the tendon. These nodules are very slow to heal spontaneously. The analysis of the acting forces shows that the interrupted fibres are not subjected to longitudinal forces any more but instead to compression forces (fig. 1 and 2).
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| Figure 7-1: Orientation of longitudinal fibre bundles around an intrafascial or intratendinous nodule (from Flint 1990) | Figure 7-2: Figure 2: The tension applied on the peripheral intact fibers engenders compressive forces on the central core defect (from Flint 1990). |
These forces inhibit the longitudinal organisation and the alignment of the collagen bundles. The development of nodules in Dupuytren's disease could be the consequence of the intrafascial rupture of some fibres.
Other studies have confirmed the remarkable plasticity of the contracted bands. Brandes et al (1994) have shown that the contracted fascia in patients treated with the continuous extension technique of Messina (1991, 1993) reacts to external forces with neoformation and reorientation of all tissue components to such an extent that nodules and cords are no longer clinically recognisable.
These observations plead for a functional origin of Dupuytren's disease that would arise as the consequence of normal adaptive responses to applied stimuli rather than for a tumor-like evolution.
This has practical consequences. If the contracture is an exaggerated response to mechanical stresses, then, by changing the way constraints are transmitted to the aponeurosis, we should be able to influence the evolution of the disease. This approach is encouraged by the demonstration of the plasticity of cords submitted to a continuous traction.