Treatments tried over the years with varying levels of success

Mechanical treatments

ESWT or shockwave treatment. is a non-invasive, drug free treatment that takes about five minutes. Sudden bursts of sound are directed into the palm and fingers to loosen the tightening cords pulling the fingers. The vital characteristic of a shockwave is that from zero decibels to high must happen in a few nanoseconds.

The fast moving sound wave hits the tightened cord and stretches it. Moreover, it activates stem cells to migrate to the site because through the nerves the brain has detected a problem and is instructing white blood cells to make a repair. The patient will feel the shockwaves and it will be uncomfortable, some would say painful, but do tolerate it because the nerves are sending a necessary message to the brain. An anesthetic would block that message and the immune system will not be activated.

In some cases the treatment needs to be repeated after 2 weeks. Improvements are still taking place a year after the last treatment. This is because the shockwaves are causing new cells to grow thanks to the stem cells. No side-effects have been recorded in using this technlogy for various diseases (such as kidneystones) over 40 years.

This website gives some more information on shockwave treatments.

Shockwave treatment has Nice guidance for Peyronie’s and for tennis elbow. It is also used outside
the NHS for Ledderhose and Dupuytren’s, with varying results according to some private studies in Germany.

Hyper baric chamber – As the aetiology of the cords and nodules suggests tissue damage by hypoxia (lack of oxygen) this has been tried. One report of patient improvement.

Iontophoresis Anti-inflammatory effect on the tissues. Sending a low electrical charge through the tissues, can also help deliver medication into the tissue (electromotive drug administration, EDMA).Used for Peyronie’s to get dexamethasone and verapamil into the tunica albuginea.

Laser (low lever laser) accelerates ATP production, increases micro circulation, formation of blood vessels, lymph vessels and collagen synthesis enhanced ( not wanted for Dupuytren’s?) It stimulates nerve endings to produce endorphins and thus reduces pain.

Ultrasound causes heat in the tissues by creating slight vibrations in the cells. This heat increases oxygen and blood flow, and can break the disulfide bonds in the collagen. However some people also suggest it can increase the amount of fibroblasts if used for healing in wound-areas.

Medical treatments

Acetyl L-carnitine (ALCAR) passes blood-brain barrier, anti-oxidant, neuroprotective. More effective for Peyronie’s than Tamoxifen in 1 study. Improves insulin response so may lower tissue glucose levels?

Allopurinol – Xanthine oxidase inhibitor used as gout medicine. Hypoxanthine is found in high concentrations in Dupuytren’s tissue, and allopurinol can reduce this, thus reducing the amount of free radicals in the tissues. However clinical results are not very promising, and some suggest that patients who benefited did so because their gout improved, not their Dupuytren’s.

Alteplase injections- a compound that stimulates cells in the nodules and cords to produce their own collagenase. So far it has been tried on a few Dupuytren’s and Lederhose patients who were happy about the results, but the patent for the drug is pending, so it is a long way from being widely available, if it ever gets so far.

It is already in use as ‘clot buster’ for people with blodclots, so safety studies have been done. It is in use by one doctor in Australia who claims good results, but no publications are available yet.

Blue light (LED array of 420 nm) in repeated applications inhibits TGF-β1-induced differentiation of HDF into myofibroblasts and reduces proliferation and myofibroblast contractility. However it may not be able to penetrate deep enough into larger or deeper lumps or cords to be effective

Botox injection : apart from an enzyme to smooth out wrinkles Botox also contains another enzyme, that is capable of reducing contractions, adhesions and fibrosis, after surgery.

Bromelain derived from pineapples, has anti-inflammatory properties and 2 different proteolytic enzymes.

Caffeine– increases, cAMP which reduces fibrosing. Also reduces TGFß and induces CCN2 expression by blocking SMAD activator, promotes PPAR-ɤ inhibition of CCN2.

Cellulose implants or fat grafts after fasciectomy. The idea is that the cord can’t grow together as easily if there is a barrier between the cut edges. There is also some suggestion that fat from different areas of the body can have different biochemical reactions to fat near Dupuytren’s cords ( some suggest fibroblasts may come out of local fat, or local fat produces TGFβ), thus reducing the chance of recurrence. This treatment is in use or being trialled.

Co-enzyme Q10 important in the ATP ( cell energy) chain. Synthesis is reduced with beta-blockers and statins. Found in skin fibroblasts. Anti-oxidant.

Colchicine gave relief to some Peyronie’s patients when taken oral 3-5 months. It can induce collagenase activity and decrease collagen synthesis

Copper (Cu) necessary for the function of superoxide dismutase and cytochrome oxidase

Curcumin via TGFß – induced CCN2 expression is inhibited by PPAR-γ curcumin stimulates PPAR-γ expression

DMSO Dimethyl Sulfoxide a good solvent, penetrates the skin easily and takes other products with it. Analgesic, anti-inflammatory, anti-oxidant. Can cause halitosis (garlic-breath)

Flaxseed ( high levels Omega3 fatty acids) anti-oxidant, increases radiation tolerance in healthy tissues

5 fluoro-uracil – injected into the wound after surgery can limit scarring

Ginseng inhibits TGFß

Hyaluronidase hyaluronan is a GAG found in healing wounds, contains glucosamines. Used as injection now and then similar to the way Collagenase injections are used. Can also be used as ointment.

Heparinoid works on destroying blood clots and platelet functions.

Imiquinol downregulates TGFß and bFGF

Interferon some types, esp IFN- ɤ but also IFN-α2b can suppress fibroblast contraction, down regulating mRNA for Actin and Fibronectin. However some patient’s cells seem more sensitive than others. Some results for Peyronie’s after intralesional injection.

MAGNESIUM is a calcium antagonist in may functions. As calcium is important for the contractility of collagen, magnesium can block the calcium receptors. Oral magnesium should only be taken if a deficiency is proven by bloodtest or on advise of a doctor, especially high doses. Some patients use magnesium oil for their hands and feet, and have reported increased mobility with that.

MSM methylsulfonylmethane or DMSO2 source of dietary sulfur, used  topically a solvent for other agents to penetrate the skin. Some  suggestion of anti-inflammatory effects.

NAC (N-Acetyl-L-Cystine) abrogates TGFß signaling and  fibrogenesis

Nattokinase ‘clot buster’ or ‘blood thinner’ has amyloid degrading effects

Nicotine has been shown to inhibit myofibroblast differentiation in the  human gingiva ( mouth), and thus slow healing of wounds.

Para-amino benzoate (PABA) used for Peyronie’s . Absorbs UVB light (n used in sunscreens, stopped due to allergic reactions) . Precursor of folate but humans can’t convert it into folate.
Considered non essential as food ingredient. Potassium salts called ‘Potaba’ thought to increase O2 uptake in tissues thus increasing function of Mono amino oxidase, which breaks down fibrous tissue. May cause drop in blood sugar levels so take with full meal.

Pentoxifyllin antagonises the effect of TGFß1

Potassium Amino Benzoate It is not fully understood how potassium aminobenzoate helps break down fibrous tissue. It is thought to increase the amount of oxygen taken up into the tissues. Oxygen is required for a chemical in the body called monoamine oxidase (MAO) to function. MAO acts to break down fibrous tissue. By increasing the levels of oxygen, potassium aminobenzoate is thought to increase the activity of MAO on hard and fibrous tissue

Procarbazine (Natulan) A cytotoxic alkalising agent, tried in the 1960’s and 1970’s, showed great promise apart from the toxic effects ( sterility after Peyronie’s treatment for example). Chemotherapy drug with all the normal side effects, changes in the bloodcells, hairloss, vomiting etc.

Quersetin a flavenoid, suspected of having anti-inflammatory and mast cell inhibitory properties.

SSKI or (super saturated) Potassium Iodide ‘iodine helps your body metabolise oestrone (a form of oestrogen able to induce tumours) and 16-α hydroxy oestrone ( a more carcinogenic form) into estriol,
a neutral or maybe even anti-carcinogenic form of human oestrogen. If taken orally the patients thyroid level needs to be monitored as extra iodine can cause an increase in thyroid hormone. For Dupuytren’s it is usually mixed 50-50 with DMSO to improve penetration. Supposed to have an anti-fibrotic effect. Results are said to be seen after (sometimes) a year or more of applying it. (also used: 1 part DMSO, 3 Vitamin E capsules, 9 parts SSKI)

Statins have anti-inflammatory anti-oxidant immune-modulating and anti-fibrotic effect through attenuation of CCN2 expression

Superoxide dismutase catches away free radicals which helps lower TGFß1

Tamoxifen lowers TGFß which decreases collagen synthesis, inhibits fibroblast production Not used because of potential serious side effects such as stroke-risk. More promising is the idea of converting
the presentation into a gel or ointment for local application.

Triamcinolone modulates TGFß and reduces inflammation ( steroid injection)

Verapamil (calcium channel blocker), reduces production of extracellular matrix by fibroblasts and fibroblast proliferation, increases collagenase activity and reduces the production of fibrogenic cytokines. In clinical use for Peyronie’s and sometimes tried for Ledderhose or Dupuytren’s, mainly in gel-form ( but the penetration may be a problem then), sometimes as injection (but the trauma caused by repeated injections is a worry in those cases).

Vitamin C necessary for fibrogenesis ( scurvy when deficient). Anti oxidant properties

Vitamin E and other anti-oxidants (propolis, blueberry, Red wine, tomatoes) have anti-inflammatory properties,Vitamin E also is a free radical scavenger, it affects protein kinase C which causes slow down of muscle growth, it affects macrophage gene expression of scavenger receptors, and thus modulates expression of Connective Tissue Growth Factor (CTGF). Lastly it inhibits platelet aggregation and prevents fat oxidation.

Glossary:

CCN2: connective tissue growth factor overexpressed in fibrotic disease, same as TGFß

TNFα tumour necrosis factor reduces basal CCN2 expression in some cells, but stimulates it in others.

TGFß and TNFα induce expression of COX 1 and 2 ( cyclo-oxygenase) which catalyses the production of prostaglandins from arachidonic acid. Cox 2 can suppress CCN2 ( can be done via cis-retinoic acid)

PG’s can activate prokinase-A and increase cAMP, which can act anti-fibrotic. However this depends on the cellsystem, as the effect can vary per organ.

Iloprost ( synthetic PG I2) elevates cAMP and antagonizes CCN2 thus acting
anti-fibrotic.