Risk factors

Risk Factors

Risk factors associated with Dupuytren’s, Ledderhose, Peyronie’s and related conditions

No one really knows what causes Dupuytren’s contracture. However, several factors have been identified that make the condition more likely, including the presence of, or a history of Ledderhose, Peyronie’s or other related conditions. The paper Clinical associations of Dupuytren’s disease provides a good starting point for people interested in understanding more about some of the links between various conditions and Dupuytren’s.

Summary

  • Having a family member with Dupuytren’s or a related condition (Genetics)
  • You have a related condition, e.g. dorsal nodules, Ledderhose or Peyronie’s
  • You have or have had a frozen shoulder
  • You are an insulin-dependent diabetic
  • You have epilepsy and take barbiturates, epanutin or phenytoin
  • You have liver disease or drink large amounts of alcohol (more than a bottle of wine per day)
  • You have high cholesterol (though more recent studies have failed to find a connection)
  • You have heart disease
  • Your thyroid gland is not working well, either producing too much or too little hormone
  • You smoke (or have smoked until recently)
  • Your age is over 50 years
  • You have HIV or cancer
  • You have had trauma to your hand or fingers, hypoxic tissues or vibration related injury or having worked with vibrating tools for more than 10 years for over 3 days per week, more than 2 hours per day (report by the Industrial Injuries Advisory Council and the Department for Work and Pensions)  Statement by the BDS: Dupuytren and vibration
  • You are taking Glucosamine or Chrondroitin supplements
  • Having Paget’s Bone Disease or Kennedy’s Disease means you are at greater risk of developing Peyronie’s and Dupuytren’s

Genetics

The most common factor is genetics. Up to 70% of people who develop Dupuytren’s contracture have a family history of the condition.

The gene (a unit of genetic material that determines your body’s characteristics) that causes Dupuytren’s contracture is passed to you from your parents. Dupuytren’s condition is an autosomal dominant disorder. This means that you only need to inherit the gene that causes it from one of your parents, rather than both of them, for you to get the condition. To date nine different genes have been identified that are associated with developing Dupuytren’s, and the way they are inherited and cause the disease is not clearly understood. We do know that the disease can skip one or more generations.

Age and sex

Other factors that make the condition more common include:

  • being male – one study found that the condition affected seven times more men than women, although women catch up and have it in equal proportion by the time both reach their 90th birthday. 
  • being over 40 years old – nearly 80% of people with Dupuytren’s contracture are between 40-70 years old
  • being of white northern European ethnicity – the condition is much less common among other ethnicities.

Diabetes

Diabetes is one of the biggest risk factors for Dupuytren’s.

Keloids_clip_image004It has long been noticed by doctors that diabetics are more likely to develop signs of Dupuytren’s Disease (up to 42 %). Although both type 2 diabetes and Dupuytren’s are more common in older people, the correlation is much greater than you would get from age alone.

Patients with Dupuytren’s have a higher chance than normal (13%) to have high blood sugar levels. However, this does not necessarily mean that Dupuyren’s causes diabetes, more that Dupuytren’s may be a symptom  of undiagnosed diabetes. but undiagnosed or unstable diabetics are more likely to develop nodules.

Diabetics with Dupuytren’s are more likely to have mild Dupuytren’s and usually don’t need surgery.

The causal relationship is unknown, but one could speculate that poor circulation in the extremities (often seen in diabetic patients) may lead to hypoxia, ischaemia and thus to increased levels of TGF and PDGF, setting the whole Dupuytren’s reaction off. Another hypothesis is that increased glucose levels can stimulate the glycolyzation of collagen, thus stimulating cords and nodules to form.

Epilepsy and  Phenobarbital (treatment for epilepsy)

It used to be believed that epilepsy was a risk factor for Dupuytren’s. It now seems more likely that the risk was actually from the medication most commonly taken for epilepsy.

Anti-epilepsy drugs like phenobarbital have been implicated in the development of DD, and in some cases the disease regressed when the medication was changed to a benzodiazepine drug. Phenobarbital and other barbiturates, epanutin and phenytoin have all been associated with the whole spectrum of Dupuytren-related diseases as well, in particular Peyronie’s and Dupuytren’s.

Phenobarbitone the association between Dupuytren’s disease and antiepileptic therapy is mediated through the peripheral stimulation of tissue growth factors and not through the central release of growth hormone or through alterations in liver metabolism. Dupuytren’s or Peyronie’s can be a side effect

Smoking

Smoking is a big risk factor for Dupuytren’s Disease.

Smoking affects the circulation, narrowing blood vessels away from the heart, and thus causing hypoxia (low oxygen) in the tissues.

Alcohol consumption and liver disease.

Drinking alcohol seems to is traditionally said to increase the risk of developing Dupuytren’s, especially for those drinking more than 5 units per week. (based on a single study from the 1950’s which compared alcoholics with liver damage to non-alcoholics),  although one study could not say for certain if it was alcohol or smoking causing the link, as most drinkers in the study smoked as well. Another  study failed to find a link between alcohol consumption and Dupuytren’s. If alcohol consumption is large enough to cause liver damage it might be another story.

There is more evidence of a link between liver cirrhosis and Dupuytren’s, where the cause of the cirrhosis was not significant. Some doctors see Dupuytren’s as an indicator of possible liver disease. A possible (though speculative) reason for the connection is that liver cirrhosis is another fibrosing disease.

HIV

A 1990 study  suggests a higher incidence in HIV positive patients, whereas another study by does not. The articles that say there is a link all quote the same study from Bower. No study was done into the medication patients were getting and whether the medication (or one of the illnesses associated with HIV) was the cause of the Dupuytren’s. More research needs to be done to clarify the situation.

Tuberculosis

A lung condition that causes hypoxia throughout the body. A study in the 1950’s showed a higher incidence of DD in TB patients, but the text of that study is not available online.

Isoniazide,an antibiotic used to treat Tuberculosis, can induce Dupuytren’s Disease and Frozen shoulders in some patients (up to 15%).  Whether this antibiotic was used in the patients described in the 1950’s study is uncertain, but the first mention of Isoniazide causing Dupuytren’s in TB patients was in 1955, so it is possible.

Glucosamine

An amino sugar that acts as precursor in the production of proteoglycans and glycosaminoglycosans (GAG’s) (present in fascia) and through increased gene expression increases collagen synthesis. Many people take it to maintain or improve joint health.

Ligament cells seemed more sensitive than tendon cells or chondrocytes, the effect was dose-dependent and high doses ( above manufacturers recommendation) could induce slight inhibition rather than stimulation.

Glucosamine can inhibit MMP (1,3,13) production.

Vitamin C

Vitamin C stimulates collagen and scar production in the body, so taking extra vitamin C for a cold or flu for instance could theoretically worsen your Dupuytren’s or Ledderhose.

Glucose

Increased glucose levels in the tissues increase the substrate for producing collagen, hence the higher incidence in people with (poorly regulated) diabetes.

Antibiotics

Isoniazide, an antibiotic used to treat Tuberculosis, can induce Dupuytren’s Disease and Frozen shoulders in some patients (up to 15%).

Tetracyclines (including doxycycline and minocycline) can inhibit collagenase, so they are contra indicated if you are having collagenase injections. They have not been specifically indicated as causing Dupuytren or any related problem, but it may be worth discussing with your doctor before taking them.

Cipro, Tequin, levaquin – fluoroquinolones can kill pancreatic beta cells ( inducing diabetes) and cause toxicity to type I collagen causing collagen degradation? They have been implicated in cases of Peyronie’s disease, and a study from 2000 by Attia et al showed that ciprofloxacin normally inhibits fibroblasts (hence the risk of Achilles tendon rupture), but Dupuytren’s fibroblasts are stimulated by it (meaning a risk of activating the disease).

Neuropharmaca

Requip (ropinirole) is associated with possible side-effects of causing or worsening Dupuytren’s and Peyronie’s. Normally prescribed for Parkinson’s and restless legs.

Ropinirole Hydrochloride is a non-ergoline dopamine agonist with high relative in vitro specificity and full intrinsic act ivity at the D2 and D3 dopamine receptor subtypes, binding with higher affinity to D3 than to D2 or D4 receptor subtypes.

Ropinirole has moderate in vitro affinity for opioid receptors. Ropinirole and its metabolites have negligible in vitro affinity for dopamine D1, 5-HT1, 5-HT2, benzodiazepine, GABA, muscarinic, alpha1-, alpha2-, and beta-adrenoreceptors.

BetaBlockers and Interferon

These have been considered as causing Dupuytren’s but more research has shown cast doubt on this. However in laboratory settings propranolol has been proven to affect collagen production by inhibiting the adrenergic suppression (Moss et al, 1979), and atenolol has a warning of Peyronie’s as potential adverse effect. Metoprolol has been implicated as inducing Dupuytren’s Contractures in an article in 2018 (Agrawal et al).

BRAF inhibitor Vemurafenib

The BRAF inhibitor Vemurafenib (Zelboraf) used for metastatic melanoma cases and for Erdheim-Chester Disease, can induce Dupuytren’s and Ledderhose as adverse effect.  While the mechanism would be interesting, we would never advise anyone to stop cancer treatment even if they developed Dupuytren’s or Ledderhose. Discuss it with your specialist if you are concerned, sometimes adjustment of the dose of medication may be possible.

Chronic heavy metal intake

In some parts of the world people can be exposed to low dose heavy metals in the drinking water or the air, through their job or naturally. Arsenicum is one of those, and chronic low dose Arsenicum intoxication has been associated with a higher percentage of Dupuytren’s Contracture, among many other problems. This does not mean Dupuytren’s can be a sign of chronic Arsenicum poisoning, as Arsenicum will cause a lot more problems, never Dupuytren’s on its own.