Epidemiology and Prevalence
Dupuytren's disease (DD) is primarily a familial disorder predominantly occurring in Northern Europe [1, 2]. For Europe, a meta-study shows a very wide prevalence range between 0.6 and 31.6% [3]. A randomized study from the Netherlands found a prevalence of 22.1% [4]. In the UK, a prevalence of 34.3 per 100,000 was demonstrated [5].
DD is a disease of older individuals, but juvenile forms and childhood occurrences also exist [6]. A meta-study of 19 studies found a prevalence of about 12% at age 55, increasing to 29% at age 75 [3]. Men are more frequently and earlier affected than women [7].
Risk Factors
Several family and twin studies suggest genetic components in the development of DD, but they do not solely cause the disease [1,2]. A variety of exogenous factors are suspected to influence the development and severity of the disease, although study findings are often contradictory. Some studies show a link with alcohol consumption, while others do not [8, 9]. Studies also do not allow clear conclusions about a connection between diabetes mellitus and DD [3, 10]. Smoking was long considered a risk factor for the development of DD (tissue hypoxia), but here too, the study findings are contradictory [3, 10, 11]. Many studies discuss the connection with manual labor (vibration) and trauma. Two studies demonstrated a positive correlation between long-term (> 15 years) use of vibrating machinery and DD [10, 12].
Dupuytren Diathesis
Some factors adversely influence the progression of DD [13]:
- Onset before age 50
- Bilateral involvement
- Positive family history
- Knuckle pads
Knuckle pads are part of superficial fibromatoses and describe localized, cushion-like fibrotic thickenings of unclear origin, located dorsally over the finger joints. With an odds ratio of 4.4, knuckle pads show the highest association with the development of DD.
Primary Intervention in DD
DD, as a fibroproliferative disease of the palmar aponeurosis, leads to increasing cord formation and, with corresponding progression, to flexion contracture of the affected finger.
In addition to conservative therapies, minimally invasive or percutaneous as well as open surgical procedures are available [14]:
- Percutaneous needle aponeurotomy
- Partial/limited aponeurectomy
- Radical/total aponeurectomy
- Dermatofasciectomy
Tubiana Staging [15]
Stage 0 | No changes |
Stage N | Nodule or cord in the palm without flexion contracture |
Stage I | Sum of flexion contracture between 0 and 45° |
Stage II | Sum of flexion contracture between 45 and 90° |
Stage III | Sum of flexion contracture between 90 and 135° |
Stage IV | Sum of flexion contracture > 135° |
The total flexion contracture of a finger is assessed in degrees, regardless of the degree of contracture of the individual joints.
Percutaneous Needle Aponeurotomy (PNA)
PNA is a procedure in which the aponeurosis cord is transected with a needle as a micro-scalpel under local anesthesia, reducing joint contracture [16]. The minimally invasive technique is considered in the early stages of DD (Tubiana I and II) unless multiple cords are affected [17]. In cases of multiple ray involvement, significant movement restriction in the proximal interphalangeal joint (PIP) and distal interphalangeal joint (DIP), higher Tubiana stages, and recurrences, minimally invasive procedures are usually not advisable.
PNA is a safe and effective measure when indicated. However, a recurrence rate of up to 85% must be expected, and recurrences occur significantly earlier [18, 19, 20]. Inadequate skin conditions and scars, as well as contractures from other pathologies, cannot be corrected with PNA, which is why the procedure is not considered for multiple aponeurosis cords and broad-based cords [21].
Partial/Limited Aponeurectomy
Partial/limited aponeurectomy is currently considered the gold standard, where the diseased tissue is surgically excised from the palm [22, 23, 24]. The indication for partial, possibly total aponeurectomy arises in cases of contracture involvement of multiple rays with significant movement restrictions in the proximal and distal interphalangeal joints (Tubiana III and IV) and recurrences [25].
For open surgical therapies of DD, complication rates between 17 and 19% are reported: permanent sensory disturbances, flexor tendon lesions, required full-thickness skin grafts due to inadequate soft tissue coverage after tenoarthrolysis, wound healing disorders, infections, hematomas, and CRPS [25, 267, 27]. Meta-analyses show average recurrence rates of 21% after aponeurectomy [28].
Dermatofasciectomy
Dermatofasciectomy dates back to the description by Busch and Lexer over 100 years ago. It involves the complete resection of skin, subcutis, and the underlying contracture cord, with the large soft tissue defect subsequently covered with a full-thickness skin graft [29, 30]. This most radical technique for the surgical treatment of DD is hardly performed anymore.
Treatment of DD with Collagenase Clostridium histolyticum
Initial treatment approaches for enzymatic dissolution of Dupuytren cords were presented as early as 1965 [31]. An example of such enzymes is collagenases, which cleave peptide bonds and thus degrade collagen.
Collagenase Clostridium histolyticum (CCH) was first introduced in 1996 in an in vitro study [32]. In this study, the enzyme was injected into surgically obtained Dupuytren cords, and their tensile strength was compared with non-injected cords. The modulus of elasticity of the CCH-treated cords decreased by 93%, reducing the force required to induce cord rupture.
CCH is injected directly into the Dupuytren cord. After the collagenase partially dissolves the collagen in the cord, the enzymatically softened cord is manually stretched the following day through passive extension of the affected cord.
In a randomized clinical phase III multicenter study from 2009 (CORD I, Collagenase Option for Reduction of Dupuytren's) with 308 patients, it was shown that patients whose cords were treated with CCH achieved significantly better results with manual stretching the following day than patients who received a placebo injection [33, 34]. The CORD II study from 2010 confirmed the results and also showed significantly higher post-interventional patient satisfaction after CCH application compared to the placebo group [35].
The CORD I study found that 96.6% of treated patients experienced at least one treatment-associated adverse event, mostly mild to moderate and self-limiting (21.2% in the placebo group):
- Swelling 72.2%
- Effusion 51.0%
- Hematoma/injection site 37.3%
- Pain/injection site 32.4%
- Pain in the upper extremity 30.9%
The indications for CCH treatment are:
- Age > 18 years
- Palpable cord
- MCP contracture 20 – 100°
- PIP contracture 20 – 80°
- Tubiana stage II
- Fixed flexion contracture: An extension deficit is required for the cord to rupture during passive stretching
Contraindications are pregnancy (no data), hypersensitivity to collagenase, and anticoagulation 7 days pre-intervention (exception: ASA up to 150 mg daily)
In patients previously operated on with partial fasciectomy with a manifest recurrence, CCH intervention shows no significant differences in effectiveness or safety compared to non-operated patients [36].
The efficiency and safety of CCH injections were investigated in 2013 by two open-label studies (JOINT I [US] and JOINT II [AUS]) on a total of 879 joints in 587 patients at 34 institutions [37]. In 57% of patients, the treatment was successful (0-5% extension within 30 days), with more MCP than PIP joints (70 vs. 37%). Joints with minor contractures responded better to CCH intervention than severe contractures, making intervention in early stages of DD more advantageous. Tendon ruptures and systemic reactions were not observed.
From the initial clinical studies (CORD I and II, JOINT I and II), patients were re-examined in a 3-year follow-up study (CORDLESS-Study: 3-year data) [38]. A recurrence occurred in 35% of the joints treated with CCH, showing the recurrence rate to be comparable to standard surgical procedures.