Luck Classification and Related Histology

Luck described a progression of three histologic stages: proliferative , involutional , and residual, roughly corresponding to nodules, nodular cords, and nonnodular cords, respectively. The key cell is the myofibroblast , which under light microscopy resembles a fibroblast but has ultrastructural differences: stress fibers, cell membrane adhesion complexes, fibronectin fibers, smooth muscle α-actin, and other unique characteristics. The proliferative cellular stage is characterized by highly cellular, mitotic histology with randomly oriented myofibroblasts and sparse, randomly oriented collagen fibrils. Specimens of the involutional fibrocellular stage are less cellular with no mitoses, and show some parallel orientation of myofibroblasts and collagen fibrils. Residual fibrotic stage histology is characterized by relatively acellular collagen with flattened cells within areas of uniformly oriented densely packed collagen bundles. Occluded microvessels and basal lamina thickening are also present in cords, nodules, and perinodular areas.

Luck staging correlates with collagen type. Normal palmar fascia has little or no type III collagen. Abnormally high levels of type III collagen exist in the palmar fascia of DD patients even in the absence of contracture. The ratio of type III to type I collagen is highest in the proliferative stage (>35%). This ratio decreases to the range of 20 to 35% in involutional specimens, and to less than 20% in residual specimens. Type III collagen persists in affected tissues: the involutional stage is static, but not normal.

Luck staging correlates with recurrence rate after fasciectomy. Balaguer et al analyzed outcomes at 8 to 9 years after fasciectomy and reported that proliferative histology more than doubled recurrence compared to involutional histology and more than tripled recurrence compared to residual histology. This Luck stage parallels clinical assessment of nodularity and may prove applicable for preoperative recurrence prediction or for procedures performed without tissue sampling.

Tubiana Staging

The Tubiana stage is an index of composite flexion contracture. The composite MCP + PIP joint flexion contracture of each ray is placed in a group of 45-degree increments:

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  Stage 0: no contracture

  
  
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  Stage 1: 0 to 45 degrees

  
  
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  Stage 2: 45 to 90 degrees

  
  
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  Stage 3: 90 to 135 degrees

  
  
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  Stage 4: greater than 135 degrees

This classification has been modified to include notations for the presence of nodules or distal IP hyperextension for each ray, and a summary number for the entire hand as well as other notations ; however, the most common use is as a quick descriptor—the stage number of the affected finger. This classification has the unique advantage of summarizing contractures from cords that span both MCP and PIP joints and complements individual joint measurements. A variation of the Tubiana stage is the total contracture index (TCI), which is the composite MCP + PIP flexion contracture in degrees.

Individual Joint Measurements

Range-of-motion measurement of individual joints using a goniometer might seem to be the most objective documentation. However, two DD-specific issues can result in a pattern of bias affecting individual joint measurements. First, limited joint motion from Dupuytren cords may produce static or dynamic contractures. Cords spanning sequential joints produce dynamic contractures via fasciodesis: measurements at one joint are linked to the position of the adjacent spanned joint. Grotesman found dynamic contractures in more than one-third of rays having combined MCP + PIP contractures, primarily affecting a PIP joint.

This is consistent with the report of correction of untreated PIP contractures in more than one-third of combined MCP + PIP contractures in which only the MCP joint was treated with collagenase clostridium histolyticum (CCH) injection. Cords extending to the proximal palm are affected by CMC joint position, which cannot easily be measured and can affect both MCP and PIP joint measurements in a zigzag fashion ( Figure 4.6 ). Second, although cords themselves are inelastic, they arise from soft tissues that have elastic attachments: passive range-of-motion measurements are subject to examiner bias from the force applied to the finger.

Demonstration of dynamic contractures with carpometacarpal (CMC) fasciodesis. A, Patients use a trick motion to compensate for tight fascia, flexing their ring and small CMC joints to allow metacarpophalangeal (MCP) extension. B, CMC flexion allows 10 degrees of active MCP hyperextension. C, When CMC flexion is blocked, active MCP extension is limited to 20 degrees, which in turn improves active proximal interphalangeal extension by 10 degrees. D, blocking CMC flexion changes passive MCP extension from 0 to 65 degrees.

Location of Disease

Although much has been written regarding the anatomical basis of cords, not all cord areas have been named, and published reports lack a precise, standard system to tag cord and nodule locations in the palm based on physical examination. A diagram developed for this purpose based on skin landmarks and common patterns of DD is shown in Figure 4.7 . Forms based on this are available at http://dupuytrens.org/research-publications/forms-for-documentation , and these allow documentation of initial evaluation disease location, joint measurements, and treatment details.

This diagram is based on common zones of involvement and allows standard documentation of the location of physical findings, procedures, and joint measurements. PDF versions of this as evaluation and procedure forms are available at http://dupuytrens.org/research-publications/forms-for-documentation .

Diathesis Score and Severity

Biologic severity affects the clinical course both before and after treatment. Biologic severity is reflected both in the rate of progression from diagnosis to the need for treatment and the risk of recurrence, extension, stiffness, and inflammatory reaction after treatment. Biologic severity varies greatly between individuals and is not simply contracture severity. One index of biologic severity is association with specific fibrotic conditions: that is, DDN, Peyronie, Ledderhose, frozen shoulder. Despite conflicting reports, each of these is probably associated with increased risk of DD and vice versa. Why is this?

Each of these conditions occurs where inelastic fascial structures are subjected to high peak shearing or traction forces . The author’s opinion is that there is an underlying connective tissue disorder triggered by the mechanics at each of these sites, which would explain the observed overlap of risk factors; family history of DD increases the risk both of Ledderhose and of DDN. In contrast, other fibrotic conditions, such as keloid or scleroderma, are not associated with increased DD risk and appear to have different molecular pathways.

Diathesis factors predict biologic severity. Diathesis factors include bilateral palmar disease, DDN, Ledderhose disease, positive family history, age of onset younger than 50, male gender, first ray disease, and involvement of more than two digits. There has not been full agreement on the relative importance of each, but in general, the greater the number of diathesis factors, the higher the recurrence rate after surgery. The strongest predictor of greater biologic severity is younger age of onset .

Similarly, rate of recurrence drops with greater age at the time of first treatment. Some factors, such as frozen shoulder and Peyronie disease, increase the incidence risk of DD but not the rate of recurrence after surgery. This paradox might be explained by the effect of index event bias on interpretation of recurrence data, and more clarification is needed. Diathesis factors share genetic markers. Patients with early age of onset, DDNs, and a positive family history were found to have a greater likelihood of having a high genetic risk score based on a profile of single nucleotide polymorphisms associated with DD.

Documentation of DD biologic severity should include diathesis factors: family history of DD in siblings or parents; gender; age of onset of DD; current age; age of first treatment; bilaterality of DD; number of digits involved; thumb involvement; presence of nodules; presence of DDNs; presence of Ledderhose disease; presence of Peyronie disease; and history of frozen shoulder. A high diathesis score implies three or more of these factors: age of onset younger than 50, positive family history, DDN, bilateral disease, Ledderhose.

Treatment Outcome Score

Outcome assessment is most meaningful in the context of the initial contracture. Two useful objective comparative outcome measures are the Thomine coefficient ([degrees of improvement]/[degrees of initial contracture]) and CCH success ([number of joints corrected to 5 degrees or less]/[number of treated joints]). The fact that neither adequately reflects functional change in all patients reflects the difficulty of this issue. Consider, for example, a patient with a 40-degree contracture and a patient with a 140-degree contracture. For these patients, complete correction would give the same outcome score by either measure, despite very different changes in function. A 30-degree improvement would not be considered a CCH success for either, but the first patient would likely be happier than the second. Patient satisfaction correlates poorly with range-of-motion measurements regardless. Roush and Stern reported results of surgery for recurrence in which 95% of patients were “unconditionally satisfied and stated that they would have the procedure again” despite lack of improvement in average total active motion.

Recurrence Assessment

Because recurrence is a lifetime issue, recurrence percentages are meaningless unless duration is also specified. Recurrence is most accurately described as a percent per year rate , not simply a percent, and also not an average of a broad range of follow-up intervals. Many definitions of recurrence exist. Quantitative definitions include need for repeat treatment, loss of a defined percent of initial correction, or loss of a defined number of degrees of correction. Different metrics cannot be easily compared. For example, recurrence as defined in CCH studies excludes the subset of treated patients not corrected to within 5 degrees of complete extension, a group known to have a higher recurrence rate ; this skews recurrence results favorably compared to other recurrence definitions. In addition, many published studies define recurrence qualitatively or not at all.

Not all contracture recurrence is Dupuytren recurrence. Contracture recurrence falls into three categories: early, progressive, and late ( Table 4.1 ). Early recontracture develops during the first 3 postoperative months, followed by a plateau. This pattern is not recurrent Dupuytren contracture. It is due to incomplete correction of secondary pathology at the time of treatment. Central slip laxity, oblique retinacular ligament tightness, mild PIP anterior cruciate ligament (ACL), or capsular tightness may not prevent improvement at the time of treatment, but their persistent effects result in loss of initial gains over the following weeks. Because these are static influences, their effects plateau. Progressive recontracture is a steady worsening of contracture that continues to progress after the first 3 postoperative months. This is due to inadequate treatment of primary pathology: inadequate fasciotomy/ectomy of all mechanically important cord(s).

Both severe contractures and diffuse disease are more likely to have multiple cords affecting the same joint, some of which may escape treatment. Residual cords with soft tissue attachments may stretch without becoming discontinuous and remain biologically active and contractile during the early postoperative period. Late recontracture develops after an initial period of stability lasting a year or more after treatment.

Similar to extension of disease after treatment, late recontracture is due to progression of new Dupuytren activity and represents true recurrence . Failure to clearly separate these groups has led to confusion regarding outcomes. The author recommends the definition of recurrence published by the international Dupuytren Delphi group: “an increase in joint contracture in any treated joint of at least 20 degrees at 1 year posttreatment compared to 6 weeks posttreatment . ”

Palm

The superficial palmar fascia lies in a coronal plane deep beneath the palmar subcutaneous tissue and covers a triangular area of the central palm, the proximal corner facing directly proximal. The palmaris longus tendon, when present, terminates in continuity with the fibers of this proximal corner. From this common point, four central bands of fascia extend distally toward each of the fingers. There is no central band for the thumb. Confluent proximally, these bands separate and diverge at the distal edge of the underlying transverse retinacular ligament, each following the path of the underlying ray. At the level of the distal palmar crease, the central bands are bridged transversely by the superficial transverse palmar ligament . At the radial border of the index central band, the superficial transverse palmar ligament is in continuity with the proximal first-web-space ligament , which continues to a point roughly superficial to the radial sesamoid of the thumb MCP joint. Although the superficial transverse palmar ligament appears to lie deep beneath the central bands, fibers from the central bands pass above, below, and through it. At this level, each central band branches in the following three directions.

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  Superficial fibers track superficially to merge with vertical retinacular fibers at the undersurface of the dermis in the distal palm in areas between skin flexion creases, where nodules commonly arise.

  
  
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  Intermediate fibers split transversely into two sections, which extend toward the lateral border of the base of the digit. This track of fibers is called the spiral band because fibers track around the neurovascular bundle: proximally, they are central and superficial to the bundle; distally, lateral and deep beneath it. Neurovascular spiral bundles result from involvement of these fibers.

  
  
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  Deep fibers continue dorsally to merge with the sagittally oriented interosseous fascia and pierce the transverse MP ligament to merge with fibers of the sagittal bands of the extensor mechanism. These fibers are rarely involved in contractures.

Web Spaces

A subdermal fascial layer borders the periphery of the web spaces from thumb to little finger. Fascial fibers follow the direction of this layer. The section of this structure spanning the fingers is referred to as the natatory ligament ; its continuation across the first-web space is referred to as the distal first-web-space ligament . It crosses the thumb to join fibers of the proximal first-web-space ligament over the radial sesamoid area. Fibers from the natatory ligament extend distally at the lateral base of each finger in continuity with the Grayson ligament and the lateral digit dermis.

Digits

Contradictory descriptions exist of the digital fascia anatomy because of difficulties inherent in dissecting fascial structures in the digits : fibrous strands less than 1-mm thick follow oblique curved paths; distortion from release of skin attachments are needed for exposure; distortion when fingers preserved in flexion are later straightened for dissection. Zwanenburg et al. recently reported a clarification of anatomy, as shown earlier in Figure 4.8 . The digital neurovascular structures are circumferentially enveloped within thin layers of fascia.

The traditional name for components of this envelope dorsal to the neurovascular bundle is Cleland ligament , and the traditional name for components palmar to the neurovascular bundle is Grayson ligament . These “ligaments” are actually a loose meshwork of multiple layers of crossing oblique curved fibers. There is a common zone of origin of these fibers in continuity with the retinacular ligaments of the fingers, the floor of the flexor tendon sheath, and the network of retinacular fibers that attach to the palmar digital skin. On the ulnar border of the small finger, this pattern of lateral fascial attachments continues in continuity with the abductor digiti minimi fascia and tendon. What has been described in the digits as the retrovascular band is actually a dissection artifact created by releasing skin attachments of this lateral fascial complex.

Primary Pathology

Core elements of Dupuytren biology are shared with other fibrotic diseases: myofibroblasts, collagen, cytokines, and mechanical stress on the extracellular matrix. Nodules are the most active sites of this process. Nodules arise on the palmar surface of the fascia in areas where shear forces from gripping are resisted by retinacular fibers that anchor dermis to fascia and result in local mechanical strain. Typical light microscopic changes are described in the earlier discussion of the Luck classification. The known process begins as fibroblasts in an extracellular matrix subjected to mechanical stress and in the presence of TGFβ1 differentiate into myofibroblasts.

Myofibroblast gene expression results in the appearance of new intracellular α-SMA microfilaments, large cell-matrix attachments, and intercellular junctions. Cell-matrix attachments (focal adhesions) of collagen strands to myofibroblast cell membranes signal myofibroblasts to contract in response to mechanical stress on the extracellular matrix. Individual collagen strands are folded by myofibroblast contraction, and extracellular matrix enzymes crosslink across these folds ( Figure 4.9 ).

Myofibroblast cycle of extracellular matrix (ECM) remodeling. Relaxed ( green lines ) and contracting ( red lines ) intracellular stress fibers are joined to extracellular collagen strands via focal adhesions ( green circles ) in the cell membrane. 1: Mechanical stress on the ECM triggers global contraction of all stress fibers. 2: This generates slack in individual collagen strands along lines of mechanical tension. 3: The slack collagen strands are repositioned by individual stress fibers, creating a loop. 4: ECM crosslinking enzymes (yellow triangle) join the base of the loop and trim the redundant strand. 5: The strand is released into the ECM. 6: The shortened strand then stress shields the stress fibers, allowing the cell to return to its prior state and repeat the cycle.

This process progressively shortens the extracellular collagen matrix at a rate up to 1 cm/month and stiffens the extracellular matrix through collagen crosslinking. The stiffened matrix transmits mechanical forces to adjacent tissues, which then undergo the same process. Under normal conditions, myofibroblast presence is temporary, limited by myofibroblast dedifferentiation or apoptosis triggered by loss of mechanical and cytokine stimulation. However, in DD, myofibroblasts persist through periods of diminished stimulation. The mechanism by which myofibroblasts resist apoptosis remains unknown.

It is believed that cords develop as a reactive process along lines of mechanical stress in susceptible tissues. The reason for individual susceptibility is unknown, but the profile of Dupuytren-type abnormalities found in phenotypically normal areas of palmar fascia prior to clinical disease include abnormally increased levels of type III collagen, abnormal mechanical stress–strain curves, abnormal tension-related contraction, DNA alterations, and some, but not all, Dupuytren-related gene expression markers.

Mechanical and gene expression characteristics of nodules, cords, and macroscopically normal palmar fascia in Dupuytren patients are all abnormal, but to different degrees. There is growing understanding of the biomechanics of fascial response to strain, age, and the cause-and-effect relationships of type III collagen to DD. The starting point could be the abnormal presence of type III collagen, mechanically different than type I, triggering abnormal mechanoregulatory stimulation of gene expression. Alternatively, the priming event might be abnormal mechanoregulation of gene activation resulting in overexpression of type III collagen.

Patterns of contracture may have more to do with collagen crosslinking than myofibroblast contraction. Some locations (i.e., distal palm, palmar digit) produce clinical contractures, but other common locations (i.e., DDN, Ledderhose) do not, despite the fact that biopsy tissue from each contracts similarly in vitro. A possible explanation is that Dupuytren biology fixes tissues in their resting position . The biology of collagen deposition and remodeling is activated by mechanical stress, but then continues during periods of rest. At rest, activated myofibroblasts and collagen crosslinking enzymes in the extracellular matrix shorten redundant collagen fibrils. At rest, this process remodels collagen length to match the resting dimension—similar to contracture of the PIP volar plate, which occurs after injury and prolonged flexion.

Such a process would be expected to produce contractures resembling the resting posture of the hand—flexion and adduction—which is what is seen in the vast majority of cases. It would also explain why knuckle pads and Ledderhose rarely develop contractures, because the IP joints rest in flexion and the metatarsophalangeal joints of the toes rest in extension.

Most patterns of DC can be explained as transformation of existing fascial structures through Luck’s stages into fibrous cords, guided by stress and stress shielding. In the process of cord formation, there is a reorientation of collagen fibers parallel to lines of mechanical stress. Any palmar fascial structure subjected to mechanical stress may contribute to Dupuytren cords. Stress shielding reduces the risk of contracture of certain locations, some of which have only minimal case reports of involvement. Structures rarely involved because of stress shielding include the Cleland ligament (shielded by adjacent phalanx); longitudinal fibers deep beneath the transverse superficial palmar ligament (shielded by the central band); transverse superficial palmar ligament (shielded by the transverse metacarpal ligament); and the septa of Legueu and Juvara (shielded by adjacent metacarpal). Stress shielding also provides the endpoint for disease progression.

As contractures progress, stress shielding from lack of use or from secondary capsuloligamentous joint contractures permanently removes mechanical stress from the cord; in the end, this allows myofibroblast apoptosis and progression to the final, involutional, static stage of disease.

Common cord patterns are shown in Figure 4.10 . Cords may be confined to the palm, the digit, or span both. Unlike cords that arise in the palm, cords isolated to a digit may have both proximal and distal bony attachments, making them more difficult to palpate.

Common cord patterns. A, Central digital, central palmar, distal first-web space, hypothenar, (B) lateral digital, (C) retrovascular, (D) spiral.

Common central palm cords are central palmar , spiral , and proximal first web . Common border palm cords are natatory , distal first web , hypothenar , and thenar . Thenar and hypo­thenar cords are uncommon and are usually associated with diffuse disease or aggressive biology. The majority of MCP joint contractures are a result of the effect of an isolated central cord. In contrast, the majority of PIP contractures are due to multiple digital cords , which, in order of frequency, are central digital , retrovascular , and spiral or lateral. Multiple cords can exist at the same longitudinal level in either palm or digit.

Secondary Pathology

Over time, flexed posture results in anatomic changes of joints and tendons independent of the causative cord. These issues are more likely to develop with more severe primary contractures. The PIP joint is particularly vulnerable to such changes. Contractures of the accessory collateral ligament are more common in PIP joint contractures greater than 45 degrees. Central slip attenuation contributes to extension deficit for PIP contractures greater than 60 degrees, which are less likely to achieve full correction than those with less severe contractures. Boutonnière, sagittal band rupture, or mallet deformity may develop secondary to chronic contractures. Sagittal band rupture can be difficult to diagnose in the context of a fixed MCP flexion contracture, but a key clue is MCP abduction–supination in the absence of a responsible palmar cord. Chronic rotational or lateral deformities from digital cords often persist after treatment of the primary disease.

Synergistic Pathology

Postural abnormalities from prior injury, chronic flexor tendinitis, osteoarthritis, peripheral neuropathy, intrinsic weakness, or mild spasticity are common in the senior demographic population and must be kept in mind in evaluation because they affect outcome expectations. Dupuytren disease is less common in rheumatoid patients, but it can coexist. This author has seen all of these conditions concurrent with DC, often not previously diagnosed.

Neurovascular Spiral Bundle

A neurovascular spiral bundle (i.e., spiral cord, or spiral nerve) is common in DC. Tissues that form a cord may initially describe a longitudinal path that spirals around a straight neurovascular bundle (see Figure 4.10 ). When this path tightens and straightens, the neurovascular bundle is displaced into a spiral path, raising a section of the bundle into a subcutaneous position that is superficial to the cord. If the neurovascular fat pad surrounding the bundle is displaced as well, this presents as an area where a palpable subdermal cord passes beneath a soft subcutaneous mass beneath soft skin. Such a finding is associated with a spiral bundle in the majority of cases, but lack of this finding is not predictive of absence of a spiral bundle.

Spiral bundles have been reported in nearly half of Dupuytren finger contractures. Superficial displacement is most common between the distal palmar crease and the flexion crease of the PIP joint. Variations occur, including cords that pass between the digital nerve and a dorsal branch, double spirals, and spirals at the level of the middle phalanx. Spiral bundles are at risk for inadvertent injury during open or percutaneous procedures.

Little Finger PIP Joint

Little finger PIP joint contractures have a worse prognosis and higher recurrence rate than other PIP joints, independent of surgical technique. Abductor digiti minimi (ADM) tendon involvement, common in little finger contractures, is not an independent risk factor for either inferior outcome or higher recurrence, and similar intrinsic tendon involvement can occur in any digit. ADM fascia involvement may explain loss of little finger supination frequently seen by this author with mild contractures.