Therapies that we are considering as research or experimental
TNF as therapeutic target
Myofibroblasts are involved in building the cords that prevent stretching of the Dupuytren affected finger and are possibly also active in the contracture itself. To down-regulate myofibroblast differentiation and activity ihe tumor necrosis factor TNF, a cell signaling protein (cytokine), may be a potential target for a therapy (LS Verjee et al. "Unraveling the signaling pathways promoting fibrosis in Dupuytren's disease reveals TNF as a therapeutic target" Proc Natl Acad Sci USA 110 (2013) E928-37 abstract). First results in a Phase 2a clinical dose-ranging trial involving 28 patients, where for some of those patients nodules were injected with a TNF inibitor, showed that an involved bio indicator reacted as expected (J Nanchahal et al. 2018 full text). Further studies are required to analyse the effect on Dpuytren contracture, its possible improvement or slow down, and potential side effects.
Injection of alteplase
A recombinant tissue plasminogen activator is injected into the cord to activate body production of collagenase. This might help to soften cords thus reducing functional impairment. The treatment has been tested on patients suffering from Dupuytren's or Ledderhose disease "In general terms, at least 95% of the patient's suffering from Dupuytren's disease have reported satisfaction with the outcome after one or two rounds of treatment due to a greatly increased range of motion in the affected digits/regions." "Patients suffering from Ledderhose disease ... reported complete satisfaction with the return to function of the affected tissue."
It is important that for patients with contracture the injection might bring some relief and increased range of motion but patients might still require surgery or NA to fully release the affected finger. Also, we could not find any long term data, very little on side effects and nothing on recurrence.
This treatment is subject to a patent and has not yet been approved by the FDA.
Shock waves, similar to the ones that are used to destroy renal stones, but with about 1/10 of the energy, are occasionally used to treat IPP (Peyronie's), Dupuytren's contracture, and Ledderhose disease. While they seem to work for IPP, and there is some anecdotal evidence of a satisfying result for Ledderhose, we have seen no scientific proof of generally good results for treating Morbus Ledderhose or Dupuytrens. The only English literature that we found (J. Haist "Extracorporal Shock Wave Therapy in the Treatment of Dupuytren's and Ledderhose's Contraction" Abstracts of the 2nd International Congress of the European Society for Musculoskeletal Shock Wave Therapy (ESMST), 27.-29.05.1999, London, Great Britain, p 55, states: "As conclusion of our results we can not advice the shock wave therapy in the therapy in the Dupuytren's or Ledderhose's contracture".
Using not the usual low energy radial shock waves but high energy focussed shock waves, a randomized trial had been performed inj 2011/12 at the German Medical University Hanover to treat Dupuytren's disease. First results on a few patients have been reported in 2012 at the annual meeting of the German hand surgeons German_link. Results show pain reduction for some aptients but other patients reported no effect. To better judge the effect of high energy focussed shock waves for Dupuytren's disease a higher number of cases and a better unterstanding of long-term sustainability and side effects are required. We have not seen any follow-up or related publications since 2012 (status June 2018).
N-Acetyl-L-Cysteine (NAC, also marketed under other brand names)
NAC has been in use for decades for treating immune and respiratory deficiencies. To our knowledge it is available in the U.S. as nutritional supplement. Research indicates that NAC might also slow down or stop growth of Dupuytren tissue: Juergen Kopp et al. "N-Acetyl-L-Cysteine abrogates fibrogenic properties of fibroblasts isolated from Dupuytren's disease by blunting TGF-β signalling" J. Cell. Mol. Med. 10 (2006) pp. 157-165. Abstract and full article: NAC_link.
Above study is a laboratory study on Dupuytren cells, not a clinical study on patients. Yet this study indicates the possibility of NAC "providing a basis for a therapeutic strategy in Dupuytren's disease and other fibroproliferative disorders." Since publication of this study NAC has also been tested on patients (orally applied, typically 600 mg/day; private communication, not published). While the total number of patients is still too low for reliable statistics, first results seem promising, e.g. to avoid extension of Dupuytren to other areas after surgery or, in one case, a significant reduction of Ledderhose nodules.
Should this turn out a successful therapy it might eventually support other therapies. Effectiveness and long term effects need still to be researched and we would caution taking high dose antioxidants like NAC over a long period of time, like years (see e.g. JAMA_antioxidants ).
As no clinical data have been published yet (and probably won't be published because Juergen Kopp has moved on to another clinic and assignment) Dupuytren Society as an inital assessment collected data from patients who have taken or are taking NAC. For results see NAC data collection by Dupuytren Society.
For more details on NAC, including brand names, see wiki_NAC.
Combination of NAC with ACE inhibitors
It has been proposed to combine NAC and ACE inhibtors to reduce recurrence after surgery of Dupuytren's contracture: K. Knobloch et al. "Antifibrotic medication using a combination of N-acetyl-L-cystein (NAC) and ACE inhibitors can prevent the recurrence of Dupuytren’s disease" Medical Hypotheses 73 (2009) p 659–661 abstract . To our knowledge this is only a propsal, we are not aware of any clinical results (status Sept 2017).
Laser therapy is occasionally applied to Ledderhose (we are not aware of its application to Dupuytren). Doubts have been raised regarding the effectiveness of laser therapy but we know of Ledderhose patients that were satisfied and the nodules were successfully reduced in size. The outcome might, besides others, depend on the type of laser and is probably best for small nodules, i.e. in the initial stage of the disease. As no generally accepted statistics have been published, we consider this therapy for Ledderhose as experimental.
So far research seems to be restricted mostly to laboratory conditions, and Tamoxifen cannot be viewed as a proven therapy. "Tamoxifen, by neutralizing or downregulating TGF-β2, may prove to be a method to manipulate and control Dupuytren’s contracture in the clinical setting. Eventually, through further clinical investigation, it may be possible to halt or even reverse this progressive and debilitating disease." Cited from M. A. Kuhn, X. Wang, W. G. Payne, F. Ko, and M. C. Robson, Tamoxifen Decreases Fibroblast Function and Downregulates TGF(beta2) in Dupuytren’s Affected Palmar Fascia, Journal of Surgical Research 103(2002):146–152. - In the mean time the relevance of TGF-β2 inhibitors has been questioned: R. Tse, J. Howard, Y. Wu, and B.S. Gan "Enhanced Dupuytren’s disease fibroblast populated collagen lattice contraction is independent of endogenous active TGF-β2". BMC Musculoskelet Disord 5 (2004) p 41-48 full_article.
In high-risk, aggressive cases Tamoxifen has been tried in combination with segmental surgery. A randomized trial showed improved results of the surgical outcome when Tamoxifen was applied as adjuvant oral therapy Degreef_Miami2010. This study will continue to check for effects on recurrence (see also surgical techniques). Unfortunately, recent results presented at the Dupuytren's symposium 2012 at Leuven, Belgium, indicate that after 2 years the effect of tamoxifen already levels off, i.e. there is no long-term benefit.
Lab experiments showed that 5-fluorouracil caused a dose-dependent, selective, and specific decrease in collagen production by Dupuytren's fibroblasts. "The clinical implication is that 5-fluorouracil could possibly reduce extracellular matrix production and therefore reduce recurrence of Dupuytren's disease of the hand." NW Bulstrode et al. "5-Fluorouracil Selectively Inhibits Collagen Synthesis" Plastic & Reconstructive Surgery 116 (2005) p 209-221 abstract. - Yet a small clinical trial with 15 patients did not exhibit specific advantages of topical treatment with 5-fluorouracil: NW Bullstrode at al. "A prospective randomised clinical trial of the intra-operative use of 5-fluorouracil on the outcome of Dupuytren’s disease" J Hand Surg [Br] 29 (2004) p 18-21 abstract. - See also Sandra Kraljevic Pavelic et al. "Screening of potential prodrugs on cells derived from Dupuytren's disease patients" Biomedicine and Pharmacotherapy 63 (2009):577-85 abstract.
Three patients independently reported that intense massaging of their Ledderhose nodules over months eventually reduced the size of their nodules and improved walking. In one case this observation was confirmed by a doctor. We don't know how that worked and whether it would work for other patients. This is far from being a therapy but we consider it worth mentioning. - With respect to Dupuytren's disease and soft tissue mobilization see e.g. Larocerie-Salgado J and Davidson J "Nonoperative treatment of PIPJ flexion contractures associated with Dupuytren's disease" J Hand Surg Eur 37 (2012):722-7 abstract ; Christie WS, Puhl AA, and Lucaciu OC "Cross-frictional therapy and stretching for the treatment of palmar adhesions due to Dupuytren's contracture: a prospective case study." Man Ther. 17 (2012):479-82 abstract ; and a post from Stephen Jeffrey in our forum.
Various diets have been proposed to reduce or stop tumor growth. Whether they are beneficial for Dupuytren or Ledderhose Disease is yet completely unclear. Patients have suggested many diets to improve Dupuytren's, some even being contradictory to others, and probably you can find for any diet someone who swears it helped. Therefore we are reluctant to suggest any kind of diet for Dupuytren or Ledderhose Disease but still describe below some diets that have been discussed.
For cancer the most famous diets are possibly those based on the Warburg hypothesis. Otto Heinrich Warburg, Nobel laureate in medicine in 1931, observed that cancer cells get their energy mainly from glucose rather than by absorbing molecular oxygen from the blood, which is what normal cells do. He suggested that this faulty respiration causes cells to become cancerous (Warburg biography and wiki_article). Later research built on his thesis (Warburg revisited) and very recently results from University of Jena, Germany, confirmed his theory (Jena_article_in_German)..
Also proposed are low or zero carbohydrate diets (e.g. Wolfgang Lutz' "Living without Bread"). Again, it is unknown whether those would have any effect on Dupuytren's or Ledderhose Disease. These diets seem to be helpful mainly for diabetes and Morbus Chron. - Some patients report successful reduction of Dupuytren nodules after 6 months of a vegetarian, no alcohol, no coffee diet.
Other diets e. g. suggest a high intake of antioxidants- A patient reported that his Dupuytren nodules significantly decreased when he eat excessive amounts of tomatoes during the harvest period. This effect might be due to the high lycopene (antioxidant) content of tomatoes. Similarly, taking NAC seems to reduce growth rates and soften cords.
So far reports of successful diets provide only anecdotal evidence, no sound statistics and no comparison to control groups. We therefore consider diets as experimental and remind patients that diets may have severe side effects. Patients should also be aware that individuals may respond very differently to diets, making general diet recommendations diffcult if not dubious. This has been demonstrated for blood glucose levels (D Zeevi et al. (2015) Personalized Nutrition by Prediction of Glycemic Responses. Cell 163(5): 1079–1094) full text.
Page last modified: 11/09/2018