Epidemiology and Prevalence
Dupuytren's disease (DD) is a primarily familial disease that occurs predominantly in Northern Europe [1, 2]. For the European region, a meta-study shows a very widely scattered prevalence between 0.6 and 31.6% [3]. A randomized study from the Netherlands found a prevalence of 22.1% [4]. For Great Britain, a prevalence of 34.3 per 100,000 could be demonstrated [5].
DD is a disease of older people, but there are also juvenile forms and diseases in childhood [6]. In a meta-study of 19 works, a prevalence of approx. 12% was determined at the age of 55 years, which increases to 29% at the age of 75 years [3]. Men are affected more frequently and also earlier than women [7].
Risk Factors
Several family studies as well as twin studies suggest genetic components in the development of DD, but they do not cause the disease alone [1,2]. A variety of exogenous factors are suspected of influencing the development and severity of the disease, although the study situation is often contradictory. Thus, there are studies that show a connection with alcohol consumption, while other studies do not [8, 9]. Studies also do not allow clear conclusions about a connection between diabetes mellitus and DD [3, 10]. Smoking has long been considered a risk factor for the development of DD (tissue hypoxia), but here too the study situation is contradictory [3, 10, 11]. A large number of studies discuss the connection with manual work (vibration) and trauma. In two studies, a positive correlation could be demonstrated between the long-term (> 15 years) use of vibrating machines and DD [10, 12].
Dupuytren Diathesis
Some factors adversely influence the progression of DD [13]:
- Onset before the age of 50
- Bilateral involvement
- Positive family history
- knuckle pads
Knuckle pads belong to the superficial fibromatoses and describe circumscribed pad-like fibrotic thickenings of unclear genesis, which are located on the extensor side over the finger joints. With an odds ratio of 4.4, knuckle pads show the highest association with the development of DD.
Primary Intervention for DD
DD leads as a fibroproliferative disease of the palmar aponeurosis to increasing cord formation and, with corresponding progression, to a 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
Staging according to Tubiana [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 entire flexion contracture of a finger is evaluated in degrees, regardless of how large the contracture degrees of the individual joints are.
Percutaneous Needle Aponeurotomy (PNA)
PNA is a procedure in which the aponeurotic cord is severed with a cannula as a microscalpel under local anesthesia and the joint contracture is reduced [16]. The minimally invasive technique is considered in the early stages of DD (Tubiana I and II) provided that not multiple cords are affected [17]. In case of involvement of multiple rays, pronounced restriction of movement in the proximal interphalangeal joint (PIP) as well as in the distal interphalangeal joint (DIP), in higher stages according to Tubiana, and in recurrences, minimally invasive procedures are usually not useful.
PNA is a safe and effective measure given the indication. However, a recurrence rate of up to 85% must be expected, and recurrences also occur significantly earlier [18, 19, 20]. Inadequate skin conditions and scars as well as contractures of other pathologies cannot be corrected with PNA, which is why the procedure is not considered for multiple aponeurotic cords and broad-based cord [21].
Partial/Limited Aponeurectomy
Partial/limited aponeurectomy is currently considered the gold standard, in which the diseased tissue is openly surgically excised from the palm [22, 23, 24]. The indication for a partial, possibly also total aponeurectomy arises in case of contracture involvement of multiple rays with pronounced movement restrictions in the proximal and distal interphalangeal joint (Tubiana III and IV) as well as in 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 insufficient 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, and the large soft tissue defect is then covered with a full-thickness skin graft [29, 30]. This most radical technique for the surgical treatment of DD is probably hardly performed anymore.
Treatment of DD with Collagenase Clostridium histolyticum
First treatment approaches for the enzymatic dissolution of Dupuytren's cords were presented as early as 1965 [31]. An example of such enzymes are collagenases, which cleave peptide bonds and thus can degrade collagens.
Collagenase Clostridium histolyticum (CCH) was first presented in 1996 in the context of an in-vitro study [32]. In this study, the enzyme was injected into surgically obtained Dupuytren's cords and their tensile strength was compared with non-injected cords. The modulus of elasticity of the CCH-treated cords decreased by 93%, thus reducing the force required to cause a cord rupture.
CCH is injected directly into the Dupuytren's cord. After the collagenase has partially dissolved the collagens in the cord, the enzymatic weakened cord is manually stretched the following day by 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 could be shown that in patients whose cords were treated with CCH, the manual stretching the next day led to significantly better results than in patients who were injected with a placebo [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 showed that 96.6% of treated patients experienced at least one treatment-associated adverse side effect, 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 a prerequisite so that the cord ruptures during passive stretching
Contraindications are pregnancy (no data), hypersensitivity to collagenase, and anticoagulation 7 days pre-interventionally (exception: ASA up to 150 mg daily)
In patients already pre-operated with partial fasciectomy with a manifest recurrence, the CCH intervention shows no significant differences regarding effectiveness or safety compared to non-pre-operated patients [36].
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), this in more MCP than PIP joints (70 vs. 37%). Joints with minor contractures responded better to CCH intervention than pronounced contractures, which is why intervention in early stages of DD is more advantageous. Tendon ruptures and systemic reactions were not observed.
From the first clinical studies (CORD I and II, JOINT I and II), the patients were re-examined in the context of a 3-year follow-up study (CORDLESS-Study: 3-year data) [38]. Recurrence occurred in 35% of the joints treated with CCH, making the recurrence rate comparable to standard surgical procedures.