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SPECIAL REPORT

Managing Dupuytren’s Contracture

Managing Dupuytren’s Contracture Shrouded in the Mists of Time Dupuytren’s Diathesis: an Elusive Condition Diagnosis and Treatment of Dupuytren’s Disease and Contracture Dupuytren’s Contracture Can Be Managed

Published by Global Business Media


Use your expertise to release the hold of Dupuytren’s contracture with XIAPEX1

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Proven efficacy: 85% of all joints injected (172/203) showed clinical improvement*2 Sustained efficacy: 87% of joints (543/623) that achieved full correction required no further medical/surgical intervention at 4 years3 Resumption of normal activities: The median time to recovery was 4 days4 Cost comparison: Cost of treatment compares favourably to fasciectomy5

Choose Xiapex – proven to be an effective and well-tolerated non-surgical treatment for your patients with Dupuytren’s contracture1 XIAPEX® Abbreviated Prescribing Information: (See XIAPEX Summary of Product characteristics for full Prescribing Information) Presentation: Powder and solvent for solution for injection for intralesional use. The vial of powder contains 0.9 mg collagenase clostridium histolyticum. The powder is a white lyophilised powder and the solvent is a clear colourless solution. Indications: Treatment of Dupuytren’s contracture in adult patients with a palpable cord. Dosage: Xiapex must be administered by a physician appropriately trained in the correct administration of the product and experienced in the diagnosis and management of Dupuytren’s disease. The recommended dose of Xiapex is 0.58mg per injection into a palpable Dupuytren’s cord. For an MP joint, each dose is administered in an injection volume of 0.25ml (requiring 0.39ml solvent for reconstitution). For a PIP joint, each dose is administered in an injection volume of 0.20ml (requiring 0.31ml solvent for reconstitution). Approximately 24 hours after injection, a finger extension procedure may be performed to facilitate cord disruption. If a satisfactory response has not been achieved, injections and finger extension procedures may be repeated up to 3 times per cord at approximately 4-week intervals. Only one cord must be treated at a time. Contraindications: Hypersensitivity to the active substance or to any of the excipients.Warnings and Precautions: Allergic reactions - 17% of Xiapex-treated patients in phase 3 placebo-controlled clinical studies had mild allergic reactions (i.e. pruritus). Physicians must be prepared to address any severe local or systemic allergic reactions including the potential for anaphylaxis following injection, including the potential for such reactions following repeated use. Whilst there is no evidence from the clinical data of an increased risk of serious allergic reactions upon repeated injections, the potential for such reactions following repeated use cannot be excluded. Tendon rupture or other serious injury to the injected extremity – Injection of Xiapex into collagen containing structures of the hand other than the Dupuytren’s cord may result in damage to those structures including possible tendon rupture or ligament damage. Injections into cords affecting the PIP

joint of the 5th finger must not be more than 2 to 3 mm in depth and not more than 4mm distal to the palmar digital crease. Patients should be instructed to contact their physician in case of symptoms of tendon rupture. Use in patients with coagulation disorders – Xiapex must be used in caution in patients with coagulation disorders or those taking anticoagulants. Use of Xiapex in patients who have received anticoagulants (with the exception of up to 150mg acetylsalicylic acid daily) within 7 days prior to receiving an injection of Xiapex is not recommended. Immunogenicity - As with any non-human protein medicinal product, patients may develop antibodies to the therapeutic protein. Since the enzymes in Xiapex have some sequence homology with human matrix metalloproteinases (MMPs), antidrug antibodies could theoretically interfere with human MMPs. No safety concerns related to the inhibition of endogenous MMPs have been observed, in particular no adverse events indicating the development or exacerbation of autoimmune diseases or the development of a musculoskeletal syndrome but the potential for it to occur cannot be excluded. If this syndrome were to develop, it would occur progressively and is characterised by one or more of the following signs and symptoms: arthralgia, myalgia, joint stiffness, stiffness of the shoulders, hand oedema, palmar fibrosis and thickening or nodules forming in the tendons. Long-term safety - Long-term safety of Xiapex is not fully characterised. The impact of treatment with Xiapex on subsequent surgery, if needed, is not known. Drug Interactions: Use of Xiapex in patients who have received tetracycline antibiotics e.g. doxycycline, within 14 days prior to receiving an injection of Xiapex is not recommended. Pregnancy & Lactation: Not recommended in pregnancy. Xiapex can be used during breast feeding. Driving and operating machinery: Xiapex may have a major influence on the ability to drive and use machines due to swelling and pain in the treated hand. Other minor influences include dizziness, paraesthesia, hypoesthesia, and headache, see side effects. Patients must be instructed to avoid potentially hazardous tasks such as driving or using machines until it is safe to do so or as advised by the physician. Side Effects: In clinical trials, the most frequently reported adverse reactions during Xiapex

therapy were local injection site reactions such as oedema peripheral (local to the injection site), contusion (including ecchymosis), injection site haemorrhage and injection site pain. Injection site reactions were very common, occurring in the vast majority of patients, were mostly mild to moderate in severity and generally subsided within 1-2 weeks post injection. Serious adverse reactions of tendon rupture, tendonitis, other ligament injury and complex regional pain syndrome related to the medicinal product were reported. Very commonly reported adverse reactions include lymphadenopathy, pruritus, ecchymosis, pain in extremity, oedema peripheral (including injection site oedema and oedema), injection site haemorrhage, injection site pain, injection site swelling, tenderness, contusion. Commonly reported adverse reactions include lymph node pain, paresthesia, hypoesthesia, burning sensation, dizziness, headache, nausea, blood blister, blister, rash, erythema, hyperhidrosis, arthralgia, joint swelling, myalgia, axillary pain, inflammation, injection site inflammation, swelling, injection site erythema, injection site pruritus, injection site warmth, injection site vesicles, skin laceration. Overdose: Overdose is expected to be associated with increased local injection site reactions. Provide routine supportive care and treat symptomatically. Legal Category: POM. Marketing Authorisation Holder: Swedish Orphan Biovitrum AB (publ), SE-112 76 Stockholm, Sweden. Package Quantities, Marketing Authorisation Numbers and Basic NHS Price: XIAPEX 0.9mg powder and solvent for solution for injection, EU/1/11/671/001, £650.00. Further information is available on request from: SOBI Ltd. 1 Fordham House Court, Fordham House Estate, Newmarket Road, Fordham, Cambs. CB7 5LL. Tel: 01638 722380. Date of Preparation: April 2014. Company Reference: SOBIUK/XIA/2014/0008(1)

Adverse events should be reported. Reporting forms and information can be found at: www.mhra.gov.uk/yellowcard Adverse events should also be reported to SOBI Ltd by email: drugsafety@sobi.com

References 1. Xiapex Summary of Product Characteristics. November 2013. 2. Hurst LC, Badalamente MA, Hentz VR et al. N Engl J Med 2009; 361(10):968–79. 3. Hotchkiss RN et al. Paper 79 Presented at ASSH, Oct 2013. 4. Warwick D et al. The Journal of Hand Surgery (European Volume) 2014:1-9 DOI: 10.1177/1753193413519926. 5. Mehta S, Belcher HJCR. Journal of Plastic, Reconstructive & Aesthetic Surgery (2014), http://dx.doi.org/10.1016/j.bjps.2013.12.030. SOBIUK/XIA/2014/0028 Date of preparation: July 2014 *Clinical improvement was defined as a reduction in contracture of 50% or more from baseline 30 days after the last injection


SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

SPECIAL REPORT

Managing Dupuytren’s Contracture

Managing Dupuytren’s Contracture

Contents

Shrouded in the Mists of Time Dupuytren’s Diathesis: an Elusive Condition Diagnosis and Treatment of Dupuytren’s Disease and Contracture Dupuytren’s Contracture Can Be Managed

Foreword

2

John Hancock, Editor

Managing Dupuytren’s Contracture

3

Anne Sjoukje Schurer MRCVS, Head of the British Dupuytren’s Society

Published by Global Business Media

Published by Global Business Media Global Business Media Limited 62 The Street Ashtead Surrey KT21 1AT United Kingdom Switchboard: +44 (0)1737 850 939 Fax: +44 (0)1737 851 952 Email: info@globalbusinessmedia.org Website: www.globalbusinessmedia.org Publisher Kevin Bell Business Development Director Marie-Anne Brooks Editor John Hancock Senior Project Manager Steve Banks Advertising Executives Michael McCarthy Abigail Coombes Production Manager Paul Davies For further information visit: www.globalbusinessmedia.org The opinions and views expressed in the editorial content in this publication are those of the authors alone and do not necessarily represent the views of any organisation with which they may be associated. Material in advertisements and promotional features may be considered to represent the views of the advertisers and promoters. The views and opinions expressed in this publication do not necessarily express the views of the Publishers or the Editor. While every care has been taken in the preparation of this publication, neither the Publishers nor the Editor are responsible for such opinions and views or for any inaccuracies in the articles.

Symptoms When to Treat the Disease Early – Especially in the Young Some Sample Case-Studies A Variety of Treatments Help is at Hand

Shrouded in the Mists of Time

7

John Hancock, Editor

What is Dupuytren’s Contracture? Symptoms of the Condition History of the Condition Who is Affected by Dupuytren’s Contracture?

Dupuytren’s Diathesis: an Elusive Condition

9

Camilla Slade, Staff Writer

Causes Unknown Where it Occurs and When it Originated Associated Conditions Factors That Increase Risk

Diagnosis and Treatment of Dupuytren’s Disease and Contracture

11

Peter Dunwell, Medical Correspondent

Whether or not to Treat the Condition Diagnosis Nonsurgical Treatments Surgical Treatments

Dupuytren’s Contracture Can Be Managed

13

John Hancock, Editor

A Manageable Condition Progress of the Disease Normal Living is Very Achievable Backup, Research and Alternative Treatments

References 15

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Foreword I

T’S A condition that affects millions of people

something of its history, both the clinical facts and

and yet very little is known about what causes it;

the myths that have grown up related to its obvious

still less about how it could be cured. Dupuytren’s

physical effects. Camilla Slade then looks at the

disease is a genetic and progressive condition,

wider range of conditions that might be associated

the main symptom of which is the inwardly curved

with Dupuytren’s and what other conditions might

fingers of Dupuyten’s contracture, which can

trigger the latent genetic malfunction that leads

progressively make even the simplest of manual

to Dupuytren’s. Peter Dunwell continues with

tasks nigh on impossible. This condition has been

an examination of the diagnosis of Dupuytren’s

known for hundreds, possibly thousands of years

disease, the physical signs that the clinician can

and people seem to have found ways of coping with

observe, conditions that might predispose a patient

the condition and its manifestations. Since Baron

to Dupuytren’s and the lifestyle factors that might

Gillaume Dupuytren wrote about the condition

trigger the onset of the condition. He also looks at

that bears his name, we have known what it is

available treatments and how they work. Finally

although, in truth, have hardly progressed at all in

we look at how people can live with and manage

understanding its causes or how it could be cured.

Dupuytren’s, including some surprising examples of

Like many conditions it is probably incurable but

those who have continued exceptionally busy lives

can be managed.

with the condition.

This Special Report opens with an article that looks at

It is often associated with older age and affects a

the symptoms and treatment of Dupuytren’s disease

relatively small proportion of a limited genetic pool,

by Anne Sjoukje Schurer MRCVS, Head of the British

but there is no doubt that Dupuytren’s contracture

Dupuytren’s Society. It goes on to give some example

deserves to be considered more carefully.

case studies relating to the disease and provides details of where further information about the disease and its treatment can be found. The following piece attempts to establish what Dupuytren’s disease is, what it does to people and

John Hancock Editor

John Hancock has been Editing Primary Care Reports since launch. A journalist for 25 years, John has written and edited articles, papers and books on a range of medical and management topics. Subjects have included management of long-term conditions, elective and non-elective surgery, Schizophrenia, health risks of travel, local health management and NHS management and reforms – including current changes.

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Managing Dupuytren’s Contracture Anne Sjoukje Schurer MRCVS, Head of the British Dupuytren’s Society

Primary Care Reports

E

VERYONE OVER fifty will know someone close to them, friend or family, with Dupuytren’s disease. You may not be aware who they are, but start asking, (politely!) or just looking at people’s hands and you’ll soon spot the woman in your dance group with bent fingers, the uncle with tight protruding cords on his palm, the young man in the office downstairs whose ring finger started curling towards his palm after he caught his wedding ring in an accident. Sometimes the inconvenience of a bent finger is small, but the condition is progressive and never goes away. For some, like professional musicians or sportsmen, even a small contracture may be a serious handicap. Each case should be considered individually as the best treatment for one person may not be the best for another.

Symptoms Let’s look at several possible cases and consider what would be the appropriate treatment. In the very early stages, Dupuytren’s presents as small nodules (or pitting) in the palm of the hand. Sometimes the nodules will be painful or itchy, sometimes they won’t: pain is not a reliable diagnostic feature. It’s the location of the nodules that is important -- Dupuytren’s nodules always occur above tendons (in the fascia). If you see a nodule or pitting and then rub across the patient’s palm with your thumb, you may feel some of the cords (which usually grow in the same direction as the bones and tendons). Then you’ll know you’re dealing with Dupuytren’s (which can be confirmed by an ultrasound scan if necessary). By the time patients are aware there is a problem, the cords are usually visible to the eye and clearly standing proud and starting to contract. If the disease is in the early stages, the best approach is often to wait and see. The condition usually develops slowly and especially in elderly patients presenting with little or no contracture, it may not become a serious problem during their lifetime. However, there are exceptions to this rule.

When to Treat the Disease Early – Especially in the Young In some patients the disease starts earlier in life, and the younger the patient is when it starts the more aggressive it tends to be. In these patients “wait and see” may not be the best solution. (Having said that, Dupuytren’s disease is wellknown for being unpredictable, and a young patient can be symptom-free for years after the first treatment, whereas the 70 year old man who never had it before may develop multiple contractures quickly after getting his first nodule, and need repeated treatments.)

Some Sample Case-Studies Simon Simon is a 38 year old professional pianist. He’s very aware of his hands and noticed the Dupuytren’s nodules before any contracture developed (an ultrasound scan confirmed the Dupuytren’s diagnosis). He’s in a very early stage of the disease, where people are usually advised to wait and see. Many early stage patients will never develop beyond this point. However, Simon’s hands are his living. Any contracture

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

In some patients the disease starts earlier in life, and the younger the patient is when it starts the more aggressive it tends to be

RECURRENCE OF DUPUYTREN’S CONTRACTURE AFTER SURGERY. NOTE THE SCARRING IN THE PALM FROM PREVIOUS OPERATION

or surgery will impair his ability to play. After doing some research, Simon decides to have radiotherapy. It is best suited for people with fast growing nodules, especially those with a more aggressive form of the disease. Once the cords have formed and started to contract, radiotherapy is far less effective. Simon is aware that his disease may progress very slowly or not at all (it could easily be six years or more before a cord appears), but he cannot afford to take the risk. He knows radiotherapy is not 100% successful, but in the majority of suitable cases it will halt the disease in its tracks or at least significantly slow down the progression. Side-effects tend to be minimal, mainly dry skin during and immediately after the treatment and after thirty years of doctors using radiotherapy there are still no reported cases of it causing cancer. Simon hopes radiotherapy can slow or halt the disease for some considerable time, and he can continue to have full use of his fingers playing the piano. Although there are NICE guidelines for radiotherapy treatment, Simon finds he can’t have it on the NHS because nobody will refer him, so he decides to have it done privately which will cost him around £1,500 per hand. (He considers the option of treatment in Germany, where it’s cheaper, but he can’t afford the time between engagements.) Margaret Margaret is 72, she’s retired, lives alone and enjoys knitting baby clothes for the premature baby unit. Her right ring finger and her little finger have bent by around 30 degrees. She can cope around the house, but the condition 4 | WWW.PRIMARYCAREREPORTS.CO.UK

is making her life more difficult. She sometimes drops things when trying to pick them up. While she is still able to knit, she finds it painful and her hands sometimes cramp up. Once, she accidentally poked her fingers into someone else’s palm while shaking hands and now she tries to avoid handshakes if possible. Doing something as simple as putting on a glove is now really difficult for her, and she has to wear mittens instead. Little things like getting her bus pass out of her handbag are almost impossible when wearing mittens. Margaret could benefit from percutaneous needle fasciotomy (PNF) or collagenase. PNF is also known as Needle Aponeurotomy (NA). PNF is done by using a syringe and needle (with local anaesthetic) to cut through the cords that are contracted and thus release the finger. With collagenase the needle is used to inject collagenase, an enzyme which weakens the collagen in the Dupuytren’s cord. When considering the two options, her surgeon explains that PNF usually lasts about two to three years, and may have a slightly higher risk of damaging a nerve, but collagenase usually lasts a bit longer and causes more short-term side-effects such as swelling and pain at the injection site. Margaret is not eager to have major surgery on her hands, as this will mean she will need help to look after herself for at least a month, and besides she would have to wait for surgery until the contractures were worse (Surgery may leave the hand scarred and this can cause problems in its own right, so surgery is normally not considered until the benefits are greater that the problems it might cause). Margaret might therefore be a good candidate to consider collagenase injections. William William is 42 years old, and has already had surgery twice – once on each hand – for Dupuytren’s contracture. Since the last surgery his left hand has developed several new nodules (surgery can sometimes trigger extension of the disease in the same way that accidental injuries to the hand can). Because William did not want any more operations he decided to wait, hoping the nodules would settle down. Unfortunately, that didn’t happen: he now has contractures in his little finger, ring finger and the middle finger, and a cord going to his index finger as well. Although he does not want any more surgery, his best option is to see an experienced surgeon who can perform dermofasciectomy (which removes both the affected fascia and a strip of skin across the top of the palm and replaces it with a skin graft – usually from the arm) with the aim of creating a ‘firebreak’ which the Dupuytren’s tissue cannot grow through. This is the only treatment that has


SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Primary Care Reports

RECURRENT, PAINFUL DUPUYTREN’S DISEASE CAN SOMETIMES ONLY BE MANAGED BY AMPUTATION OF THE AFFECTED FINGER

a chance of giving him long term relief. He is past the stage where radiotherapy might help, and PNF or collagenase will not stop the progression of the disease, only treat the cords that are already causing problems. So dermofasciectomy is his best chance of halting the disease. While he is disappointed to hear this, William decides to go for the surgery and get the use of his hand back again for as long as possible. William also has a painful nodule growing under his right foot. His GP was not sure of the diagnosis, so William was referred to a foot surgeon. The foot surgeon did an ultrasound scan and found that the nodule was situated in the fascia, after which William wondered if it could be similar to what he had in his hands? He was told yes: he has a condition called Ledderhose disease which affects the feet, and it is closely related to Dupuytren’s. Surgery can cause a lot of problems in Ledderhose cases as patients tend to produce more nodules afterwards, so William decided to go private and opt for radiotherapy. This helped to soften and shrink the nodule and stop the pain. He is now able to go cycling again without pain when pushing the pedals. John John developed a lump in his right little finger after an injury when he was 19. It hurt, but the pain settled down after a while, and he thought that was an end to it. His doctor did not know what the lump was, but they both assumed it was scar tissue. Ten years later the finger started to contract, and while John tried very hard to keep straightening it, he had to admit to being beaten by the forces of his own ‘scar tissue’, and went

to see his doctor again. His doctor referred him to a hand orthopaedic specialist, who made a tentative diagnosis of Dupuytren’s disease. John had never heard of this: nobody in the family or in his circle of friends had it. After some tests in the hospital to make sure he did not have diabetes, liver disease or heart disease (these are known to be risk factors for Dupuytren’s, and thus it was worth checking to see if he had these as well) John had a partial fasciectomy, the cord that was found was removed (and sent off for histopathology to confirm the diagnosis), and two weeks later John started occupational therapy to get the use of his little finger back. Because John was young when his Dupuytren’s started he might have had a severe or aggressive form, but he didn’t develop any other nodules for the next twenty years. So even though he started at a young age the disease stayed away for a long time, and surgery was the best option for him. In later life, John developed a frozen shoulder (a related condition) and had more problems with Dupuytren’s developing a dorsal nodule on his index finger (which was initially misdiagnosed as arthritis but finger nodules can also be one of the symptoms of Dupuytren’s.

A Variety of Treatments For many patients partial fasciectomy is currently considered to be the gold-standard treatment. It means opening the affected part of the fascia, releasing the contracture and allowing normal hand function again. It can be repeated, but each episode of surgery in the same area becomes more difficult due to scarring, and the probability of success is reduced. However,

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

While fasciectomy is still seen as the gold standard, having an injection (collagenase) which dissolves the collagen in the cords, weakening them so they can be snapped, is an important addition to the treatment arsenal for this unpredictable and incurable condition

if the patient only needs one or two treatments in his or her lifetime, this will not be a problem. Partial fasciectomy is usually done under local anaesthetic, though some cases may need a general anaesthetic. The surgeon has a good view of the operating field, making it easy to avoid nerves and tendons, and it releases the contracture better than any other treatment can. Unfortunately, in some patients the disease seems to get activated by the trauma of surgery; some patients are not suitable for a general anaesthetic; and many patients would rather have minimally invasive treatment. Thus, while fasciectomy is still seen as the gold standard, having an injection (collagenase) which dissolves the collagen in the cords, weakening them so they can be snapped, is an important addition to the treatment arsenal for this unpredictable and incurable condition. Dupuytren’s research is ongoing, and new treatments give hope to patients who are aware that this condition is partly genetic and that their children are also likely to be affected in time. Genetic research is being done to try to identify the genes responsible, and how they affect the tissue growth and biochemistry in the fascia. Work is also continuing to compare the different treatments available and assess which are most useful for specific patients.

Help is at Hand People like Simon, Margaret, William and John are not alone, but they can feel very vulnerable, especially if they don’t know much about Dupuytren’s and what it might mean for their future. Their doctor tells them not to worry,

but of course they are concerned about losing the use of their hands. For people like them, there is now a charity, the British Dupuytren’s Society (http://www.dupuytrens-society.org.uk) where they can ask for reassurance, guidance or just complain about how their hands feel and get in touch with other patients. The Society began in 2011 as a daughter organisation of the International Dupuytren’s Society. It is run by patients and has the back-up of several specialist doctors. At the moment the BDS is internet based, running a website, Facebook page and two blogs (one about the BDS, one about Ledderhose Disease), and answering any emails that come via the website from people who want some more advice or support on the condition. The Society aims to increase awareness of the condition, so that more people get diagnosed at an early stage and a decision can be made about what treatment (if any) would be suitable for them. The website has up-to-date information on treatments and where patients can get treated, as a lot of queries we get are simple things such as “Where is the nearest specialist, who performs PNF or uses collagenase near me?” We are always happy to review our list of specialists and provide links to informative sites, and do not advise one specialist over another, merely advise who is nearest and has experience with Dupuytren’s, and we always recommend people to seek advice and if necessary treatment from an expert. All patients are fictitious but are based on real cases.

Sobi is an international specialty healthcare company dedicated to rare diseases. Our mission is to develop and deliver innovative therapies and services to improve the lives of patients. The product portfolio is primarily focused on Inflammation and Genetic diseases, with two late stage biological development projects within Haemophilia. We also market a portfolio of specialty and rare disease products for partner companies. Sobi is a pioneer in biotechnology with world-class capabilities in protein biochemistry and biologics manufacturing. In 2013, Sobi had total revenues of SEK 2.2 billion (e253 M) and about 550 employees. The share (STO: SOBI) is listed on NASDAQ OMX Stockholm. More information is available at: www.sobi.com

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Shrouded in the Mists of Time John Hancock, Editor

The origins of Dupuytren’s contracture and disease might not be well known yet but its history, symptoms and who it affects are now well documented.

What is Dupuytren’s Contracture? A simple definition of Dupuytren’s contracture would be ‘a condition in which there is a fixed forward curvature of one or more fingers, caused by the development of a fibrous connection between the finger tendons and the skin of the palm’. But that understates a condition named after French surgeon, Baron Guillaume Dupuytren, one of the first people who identified and operated on the condition in the early 19th century. A better definition might be that from the Dupuytren’s Practice1; “Dupuytren’s disease is a benign condition that affects the connective tissue between the palm of the hand and the fingers. It typically starts as a small nodule (lump) and generally affects the ring or little finger, but may appear throughout the palm and sometimes on the thumb. As the disease progresses the nodules may then grow, and cords develop along the tendons. These cords then thicken which can contract and bend the affected fingers towards the palm. This can stop the fingers from being able to straighten, and is called a ‘contracture’. The progression of a contracture can be more aggressive if there is a familial history of the condition.”

Symptoms of the Condition Dupuytren’s is listed as a ‘rare disease’ on a global scale although in the mainly North European area, where it most often occurs, it is fairly common and is not a fatal condition nor is it necessarily painful but, as the condition progresses and the affected fingers fold ever further forwards, it can be inconvenient and even embarrassing. Whether one is putting on gloves or putting your hand in your pocket, Dupuytren’s can make quite simple actions difficult. Not everybody with the condition will develop contractures, in which case the condition is referred to as Dupuytren’s disease

(palmar fibromatosis) affecting the palm of the hand. Recognising Dupuytren’s contracture or disease might not seem difficult, given the visible manifestation of the full condition, but there are preliminary signs in the progressive condition and it is worth considering what Patient.co.uk regards as the things to look out for2. “At first, there is a thickening of some tissues under the skin in the palm. If the disease progresses you may develop a contracture of one or more fingers. When you have a contracture, affected fingers bend (contract) towards the palm and you cannot straighten them fully. Typically, the ring finger is usually affected first – then the little finger, and then the middle finger. It takes months or years for the condition to develop and progress to a contracture.” And although the condition usually affects the hand, the article continues to point out that, “Some people with Dupuytren’s contracture have some thickened tissue under the skin in other parts of their body. For example, a thickening on the knuckles, on the soles of the feet, or on the penis.” It can sometimes be the case that, during the early stages of Dupuytren’s contracture or disease, patients will experience burning, itching, or temporary tenderness on the palm of the hand as if it was healing following a blow or a cut. It is as if scar tissue were forming but there is no scarring. The condition can affect either or both hands and can take place over several years or, less often, over months or even weeks: development might even be intermittent.

History of the Condition Dupuytren’s disease (DD) is an ancient affliction whose exact origin is unknown3, but which has been associated with the Vikings who, in turn, introduced it to the many North European areas where they settled. Hence, there is a preponderance of cases in areas bordering the North Sea… such as Scotland, Ireland, England, France, Holland, Denmark and

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Either sex can be

leave their home on the Isle of Skye for ever. And the men did indeed suffer a curvature of their fingers, which made them unable to play the bagpipes therefore of no further use to the MacLeod’s. Perhaps more authoritatively, Dr Felix Platter practising in Basel Switzerland, in 1614 identified, though did not name, the condition in a stonemason whose left finger and little finger had contracted into his palm. It is also believed that Dr Platter later dissected the mason’s hand after death to confirm the nature of his condition.

affected by Dupuytren’s contracture but it seems to affect men more than women. Equally, while cases can be found

Who is Affected by Dupuytren’s Contracture?

across the age range, it more often occurs during later life with men over the age of 50 years and women over the age of 60 most often being affected

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Belgium. There is also a noticeable incidence of the condition in North America and Australia, presumably linked to the North European migrations with which those places were first colonised. Unsurprisingly perhaps, given the Viking origins of Dupuytren’s contracture, the highest rates of incidence of the condition are found in Scandinavian countries and the highest incidence of all in Iceland. In Scotland, what we now know as Dupuytren’s contracture was, as long ago as the 16th century, associated with ‘The Curse of the MacCrimmons’4. The curse foretold that the MacCrimmons, pipers to the chieftains of the Clan MacLeod, would have to

Either sex can be affected by Dupuytren’s contracture but it seems to affect men more than women. Equally, while cases can be found across the age range, it more often occurs during later life with men over the age of 50 years and women over the age of 60 most often being affected. As we’ve already said, the condition is most often found in people of North European descent and affects 4-6% of Caucasians worldwide 5. Some 45% of sufferers have bilateral disease, i.e. affecting both hands, while in unilateral cases, the right side is more often affected. The ring finger is the one most likely to be affected followed by the fifth digit and then the middle finger. While much about Dupuytren’s disease may not be known, that doesn’t mean that it cannot be managed to minimise the inconvenience for individuals as later articles in this paper will show.


SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Dupuytren’s Diathesis; an Elusive Condition Camilla Slade, Staff Writer

We probably know where it comes from but we haven’t yet worked out what it is

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Causes Unknown According to the UK NHS, while the exact cause of Dupuytren’s contracture (sometimes referred to as Dupuytren’s diathesis – diathesis being the disposition towards a condition) is unknown it is believed to be a genetic condition often running in families. That conjecture would certainly be supported by the reasonably well documented prevalence of the condition among people descended from the Vikings. Also not known is the reason why the tissue beneath the palm of the hand becomes thickened in the early stages of the condition. And while Dupuytren’s disease and subsequent contracture might be more common in people with other conditions such as diabetes, epilepsy and HIV or who indulge in the old villains of smoking and alcohol dependence, most Dupuytren’s sufferers have none of these conditions. As hand surgeon Keith Segalman at the Curtis National Hand Center and Greater Chesapeake Hand Specialists in Maryland explains6, “We’ve detected many associations, but no clear cause.” Not only, according to the UK NHS 7, is Dupuytren’s disease and contracture genetic, but also it is thought to be an autosomal dominant disorder, i.e. it can be passed on by either parent. It is thought that men are three times more likely than women to develop the condition (some researchers suggest the figure could be as much as 5 to 15 times more likely) although, as in so much else with Dupuytren’s, much of the reasoning as to why that could be the case is speculative. It could be clinical, related to the expression of androgen receptors in the Dupuytren fascia; the first sign in the early stages of Dupuytren’s is a lump in the palm of the hand which many people mistake for a callus or something they’ve done playing, say, golf or tennis. Or it could be related to the predominance of men in manual labour occupations where vibration exposure might play its part – see further on in this article – although hand injury or overuse of hands

does not seem to make any difference. By contrast rheumatoid arthritis seems to protect against the condition.

Where it Occurs and When it Originated Whatever the reasons, in the UK for instance, around one in six men over the age of 65 have some degree of Dupuytren’s contracture. Not only is this a condition more frequently encountered in older men of North European origin, but also it tends to be more severe and progress more rapidly in that group. But, interestingly, over the age of 80, the extent of the condition seems to be similar between men and women. Although, from its apparent origins, Dupuytren’s is often known as the ‘Viking Disease’ there are in fact nine or ten genes associated with the condition which suggests that its development could be traced back to several causes. This expanded view might be supported by the fact that evidence of Dupuytren’s has been found in Egyptian mummies8 (clearly pre-Viking) and that the other group outside of northern Europe to experience a high incidence of the condition is the Japanese. While the proportions or percentages of sufferers may not be particularly high, in a population as large as that in north-west Europe and its global diaspora, the absolute figures are considerable. As a lifelong disease affecting a limited proportion of the population, Dupuytren’s

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Smoking and excess alcohol intake are considered risk factors as is the medication for epilepsy, and injury to the hand. This latter risk might well be associated with manual labour especially when it includes vibration

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contracture or disease has a relatively low annual incidence, i.e. rate of diagnosis of new cases, but a relatively high prevalence, as once somebody has the condition it does not go away. Also, while Dupuytren’s contracture of the hand is less common among and seems to progress more slowly in younger people, the disease seems to accelerate rapidly when it affects other parts of the body such as in cases of onset at a young age with additional fibromatosis affecting the back of the hand, soles of the feet and the penis. Perhaps the only clear thing is that very little is clear with this condition and there will be many teetotal non-smoking women suffering from Dupuytren’s disease.

Associated Conditions However, as alluded to above, Dupuytren’s contracture is related to a number of similar conditions that affect different areas of the body in people with a disposition (Dupuytren’s diathesis) to the condition, including, as explained by the UK NHS9: • Garrod’s pads – nodules that develop on the back of the knuckles on the fingers • Ledderhose’s disease (plantar fibromatosis) – nodules and contractures that affect the foot • Peyronie’s disease – where the tissue of the penis is affected, causing it to become abnormally curved These conditions can occur on their own, but some people are affected by several of them at the same time. The Dupuytren’s practice10 would add to this list Plantar Fasciitis; also affecting the foot and defining “the thickening of the tough flexible band that runs under the sole of the foot. It often results in heel pain and grows gradually worse over time.” Another quite common condition associated with Dupuytren’s diathesis is frozen shoulder. Baylor University Medical Center in Dallas11 explains that, “A great variety of conditions have been associated with DD [Dupuytren’s

diathesis]. Some are tenuous relationships; others are more marked. It is generally believed that individuals with diabetes, epilepsy, chronic alcoholism, and pulmonary tuberculosis have an increased incidence and earlier onset of DD.” However, Fisk has pointed out that no variety of disease, injury, activity, or occupation could induce DD in someone who was not genetically so determined. “Among other medical conditions that have been said to be associated with DD are arthritis, diabetes mellitus, myocardial disease, reflex sympathetic dystrophy, hepatic disease, alcoholism, barbiturate ingestion, peptic ulcers, fibromatosis, compulsive personality, carpal tunnel syndrome, trigger fingers, HIV, and smoking. DD is essentially a condition of middle and later ages, and its association with many common and chronic diseases is probably more coincidental than causative.”

Factors That Increase Risk While the causes of conditions in the Dupuytren’s spectrum may not be clear, some factors that make it more likely to develop have been identified. As already mentioned above, smoking and excess alcohol intake are considered risk factors as is the medication for epilepsy, and injury to the hand. This latter risk might well be associated with manual labour especially when it includes vibration. Unfortunately, while conditions such as diabetes, epilepsy and liver disease do seem to increase the likelihood of a patient also getting Dupuytren’s disease, as with the underlying causes of condition, the nature of the links is still not understood. Among the risks above is work-related risk for people engaged in manual labour and/or using vibrating equipment. The UK Industrial Injuries Advisory Council12 has concluded that, “given sufficient exposure to hand-held vibrating tools, risks of Dupuytren’s disease and contracture can be more than doubled (the normal threshold employed by the Council when recommending prescription).”


SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Diagnosis and Treatment of Dupuytren’s Disease and Contracture Peter Dunwell, Medical Correspondent

Primary Care Reports

Ways in which the effects of Dupuytren’s disease and contracture can be reduced or eliminated

Whether or not to Treat the Condition Because the exact causes of Dupuytren’s disease and contracture remain unknown, it is also difficult to establish a preventative programme. Nevertheless, for those with a genetic predisposition to the condition, stopping smoking and cutting down or abandoning alcohol could well be beneficial. Furthermore, many cases of Dupuytren’s disease are neither painful nor do they progress to contracture and so no treatment might be necessary. Even the milder cases of Dupuytren’s contracture itself, which cause neither discomfort nor disability, may also be best left untreated. As a general rule, “Treatment is needed only if the normal function of the hand is affected – or is likely soon to become affected.”13 The Patient.co.uk article from which that is taken continues that “in about one in 10 cases, the condition improves without any treatment… The need for treatment can be reviewed from time to time.” If treatment to restore hand function and prevent progression of the disease is deemed necessary, there is a range of treatment options, both nonsurgical and surgical.

Diagnosis Before any treatment is considered, there must first be a diagnosis. A commonly used test is whether an individual is able to place their hand flat on a table top, ‘Hueston’s tabletop test’, (and, if not, the extent of any finger curling) or if their hand function is significantly affected. Other indicators are when there are areas of numbness, nodules or skin pitting and/or thickening in the palm or loss of grip strength. In diagnosis, clinicians should pay particular attention to the metacarpophalangeal (MCP) joints and the proximal interphalangeal (PIP) joints14. Though it may seem obvious, it’s worth stating that individuals, even in the early stages of Dupuytren’s disease, will experience loss of control

over their fingers and find that they can no longer hold small objects or hold any objects tightly: they gradually lose the ability to control when they bend their fingers and by how much. Clinicians need to assess the amount that someone can bend their finger (flexion) and the amount they are able to straighten it (extension).

Diagnosis should start with a thorough patient assessment including noting relevant information including age, gender, ethnicity, profession, manual hobbies and, in particular, any family history of Dupuytren’s disease with, if it is known, age of onset, symptoms, rate and course of disease progression. Other factors of which a clinician will wish to take note will include whether the patients has diabetes, epilepsy, HIV, any history of drug or alcohol abuse, and psychosocial history. The bulk of this information is less about establishing a cause and more about trying to foresee how the condition might affect the patient’s work and leisure pursuits and family life. At the end of this process the clinician and the patient together should assess the need for treatment and what might be the most suitable treatment: in the first place, whether nonsurgical or surgical treatment will be best. Both types of treatments have their benefits and drawbacks.

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Less invasive is needle fasciotomy, sometimes called needle aponeurotomy or closed fasciotomy. In this the surgeon pushes a fine needle through the skin over the contracture then uses a sharp edge of the needle to sever the tissue under the skin

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Nonsurgical Treatments Nonsurgical treatments for Dupuytren’s contracture include radiation therapy, various substances applied to the skin or ingested (none of which have been shown to work), and an injected therapy called collagenase clostridium histolyticum (commercially available in Europe and the USA). The procedure covering the injection of collagenase is sometimes known as ‘enzymatic fasciotomy’; in this procedure the enzyme is injected directly into the cords that form as a result of the disease process, and so dissolve and weaken the tissue. Following the injection procedure, after an interval of 24 hours, the clinician then applies pressure to the contracture to break the cord and, hopefully, to restore near-normal function. While this treatment has enjoyed a good success rate in reducing contractures in MCP joints, the success rate is less good with PIP joints, although this is common to surgical procedures too. There is emerging good-quality data on long-term success and recurrence rates showing that this technique is comparable to the most commonly performed types of surgery.a,b There are side effects associated with collagenase therapy for Dupuytren’s contracture, although the majority of these are minor, and spontaneously resolve within 14 days, and are typical of what would be expected from the injection of a bacterially-derived foreign protein: mainly rashes, swelling, bruising and so on. However, if the enzyme is injected into the wrong site it can cause considerable damage to the hand, and there are a few cases in the literature of tendon rupture and complex regional pain syndrome resulting from collagenase that was presumably injected into the wrong place. For this reason, the product licence for this product states that it should only be injected by “a physician appropriately trained in the correct administration of the product and experienced in the diagnosis and management of Dupuytren’s disease.”c The recovery time after collagenase injection is considerably shorter than that following limited fasciectomy – the most commonly performed surgical procedure for Dupuytren’s contracture in the UK – and patients are reported as being

able to return to work within a few days compared to several weeks following surgery.d Patient.co.uk15 describes radiation therapy for Dupuytren’s contracture as, “having several low doses of X-rays to the affected hand. The theory is that this will soften the abnormal tissue, which will then stop or slow down the progression of the disease. There is some uncertainty about how well this treatment works. However, some research studies suggest that there is a reasonable chance of this treatment working well.” However, radiation therapy for Dupuytren’s disease is not generally available on the NHS so patients would probably have to pay for private treatment. It is also only effective in patients with rapidly progressing disease, usually in the early stages. Splinting is another nonsurgical treatment with the patient’s fingers being bound to a plastic strip in the straightest position they find comfortable. It’s not a standard procedure and the factors (time and frequency of use, positioning of fingers and degree of force used to straighten them) can vary greatly. Splints are also used after surgery to aid healing.

Surgical Treatments There are two principal surgical treatments. The more traditional is open fasciotomy or partial fasciectomy in which the Dupuytren’s cord is cut or removed. To gain access to that tissue the overlying skin has to be parted and then, when the procedure is completed, stitched back together. This procedure is normally conducted under general anaesthetic. Less invasive – but not often used in the UK – is needle fasciotomy, sometimes called needle aponeurotomy. In this procedure the surgeon pushes a fine needle through the skin over the contracture then uses the sharp edge of the needle to sever the tissue under the skin, using the needle like a saw. This procedure is carried out under local anaesthetic in an outpatient clinic. It’s not always suitable but the specialist will know the conditions in which it can be applied. So while this somewhat enigmatic condition might not be curable, there are a number of things that can help patients to live with it and manage the condition, as we will see in the following article.


SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Dupuytren’s Contracture Can Be Managed John Hancock, Editor

Living with the condition is neither as difficult nor as limiting as might at first be thought

Dupuytren’s contracture may not be a lifethreatening illness but it can be more than inconvenient. Younger sufferers might find that it limits their ability in a range of occupations and not just the manual ones. Even using a keyboard will become increasingly difficult. And, while the majority of Dupuytren’s sufferers are in older age groups, with increasing numbers of people either having or choosing to work into their later years, it can still be more than an inconvenience. That said, an increasing number of people do live with the condition; but how?

A Manageable Condition According to the US National Library of Medicine16, “Although there is no cure for Dupuytren’s disease, most patients can gain significant functional improvement following corrective surgery, which is the mainstay of treatment. Indeed, hand function is worsened by increasing deformity in Dupuytren’s disease and improved by correction of the deformity.” Still sounding optimistic, “Most people with mild disease can live with it fairly well.” is the view from Better Medicine17 which continues to add, “If you need surgery, you may need to wear a splint for a certain amount of time afterwards and have physical therapy to prevent scar tissue and strengthen your hand. Physical and occupational therapy may include heat, massage, and range of motion exercises.” Nobody should be under the misunderstanding that Dupuytren’s will go away and, because it is a genetic and incurable condition, it is possible that the contracture will return at some point after even a successful treatment. Postoperative recurrence can be higher than 50%, especially after needle aponeurotomy, but, to be more optimistic, some studies

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have found that up to 12% of cases can regress without treatment.

Progress of the Disease Dupuytren’s disease is usually painless. As a result, its progress is insidious inasmuch as sufferers, not feeling any pain, tend to adjust to the slowly changing format of their hand perhaps simply putting it down to ‘getting older’. It is often only when contractures have occurred and routine activities such as housework or simple formalities such as shaking hands have become difficult or impossible that patients finally seek medical assistance. The point is that Dupuytren’s should not be ignored and there is no point in individuals trying to stretch their hands or their fingers in order to delay or counteract the condition’s progress. There are three recognisable stages in the progress of Dupuytren’s disease and contracture. The first ‘Proliferative’ stage is where a patient might experience some tenderness in the hand and, perhaps, early discomfort from movement of fingers. The next ‘Involutional’ stage is where the condition spreads along the fascia and starts to directly affect the fingers causing the cord to develop: at this stage the nodules and cord become more obvious. Finally, in the ‘Residual’ stage the condition continues to spread and the cords start to tighten, creating the contractures that typify the condition; also, at this stage, the nodules begin to disappear.

Normal Living is Very Achievable Dupuytren’s contracture can now be successfully treated with a variety of therapies, and, whatever restrictions the condition may have placed on the patient’s life prior to treatment, afterwards they may often resume normal living. A number of well-known people are popularly supposed to have, or had, Dupuytren’s

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SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Backup, Research and Alternative Treatments

James Barrie, author of Peter Pan, had Dupuytren’s and it might well have been that which inspired his villain Captain Hook. Also, Irish playwright Samuel Beckett (Waiting for Godot) had the condition as does Joanna Harris, author of the bestselling book Chocolat

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contracture and continued with demanding lives. Writer James Barrie, author of Peter Pan, had Dupuytren’s and it might well been that which inspired his villain Captain Hook. Also, Irish playwright Samuel Beckett (Waiting for Godot) had the condition, as does Joanna Harris, author of the bestselling book Chocolat. Actors Bill Nighy and David McCallum are allegedly both sufferers as was the former US President, Ronald Reagan. While serving as Prime Minister, Margaret Thatcher also had to have her hand operated on to relieve contracture at the age of 60. Perhaps most remarkably, classical pianist Misha Dichter, finding he could no longer stretch his hand to reach all the keys, realised that his family condition of Dupuytren’s had affected him. After surgery in 2007 plus some therapy he was able to resume his career as successfully as before.

People affected by Dupuytren’s disease have increasing access to treatment options and several support services. These include the International Dupuytren Society, the British Dupuytren’s Society and the Dupuytren’s Foundation. Research continues into providing new treatments for Dupuytren’s disease; collagenase is currently under consideration by NICE with a decision expected by the end of 2014. People have suffered from Dupuytren’s disease with no effective treatments, probably throughout all of human history. It is only in the last couple of hundred years that the condition has been recognised and identified for what it is, and that first surgical – and subsequently effective medical – therapies have been devised to treat the condition. Patients can now receive effective treatment from a range of surgical procedures and from collagenase injections; and research into the underlying causes of the condition will undoubtedly produce opportunities to develop new therapies in the future. Finally, the advent of the internet in the 90s has led to the instant availability of on-line help and support for both newly diagnosed and long-term sufferers from this disabling and embarrassing condition.. Dupuytren’s disease is an eminently manageable condition.


References: 1

The Dupuytren’s Practice http://www.thedupuytrenspractice.com/conditions/dupuytrens-disease/

2

Patient.co.uk http://www.patient.co.uk/health/dupuytrens-contracture-leaflet

3

Baylor University Medical Center http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1305903/

Dupuytren’s Society http://dupuytrens-society.org.uk/stories/history.html

4

Medscape http://emedicine.medscape.com/article/329414-overview

5

WebMD, Dupuytren’s Contracture: Causes and Risk Factors http://www.webmd.com/a-to-z-guides/features/dupuytrens-contracture-causes?page=2

6

7

NHS choices http://www.nhs.uk/Conditions/Dupuytrens-contracture/Pages/Causes.aspx

8

Dupuytren’s Society http://dupuytrens-society.org.uk/stories/history.html

9

NHS Choices, Dupuytren’s Contracture http://www.nhs.uk/conditions/Dupuytrens-contracture/Pages/Introduction.aspx

10

The Dupuytren’s Practice http://www.thedupuytrenspractice.com/conditions/dupuytrens-disease/

11

Baylor University Medical Center http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1305903/

UK Industrial Injuries Advisory Council https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/308651/dupuytrens-contracture-report.rtf

12

13

Patient.co.uk http://www.patient.co.uk/health/dupuytrens-contracture-leaflet

14

Physiopedia http://www.physio-pedia.com/Dupuytren%E2%80%99s_Contracture

15

Patient.co.uk http://www.patient.co.uk/health/dupuytrens-contracture-leaflet

16

US National Library of Medicine http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1963648/

Better Medicine http://www.bettermedicine.com/understanding-dupuytrens-contracture/7-things-to-know-about-dupuytrens-contracture/?redirect=beme and go to page 7

17

N Engl J Med. 2009 Sep 3;361(10):968-79. doi: 10.1056/NEJMoa0810866.

a

Injectable collagenase clostridium histolyticum for Dupuytren’s contracture.

Hurst LC1, Badalamente MA, Hentz VR, Hotchkiss RN, Kaplan FT, Meals RA, Smith TM, Rodzvilla J; CORD I Study Group. J Hand Surg Am. 2013 Jan;38(1):12-22. doi: 10.1016/j.jhsa.2012.09.028. Epub 2012 Nov 30.

b

Dupuytren contracture recurrence following treatment with collagenase clostridium histolyticum (CORDLESS study): 3-year data.

Peimer CA1, Blazar P, Coleman S, Kaplan FT, Smith T, Tursi JP, Cohen B, Kaufman GJ, Lindau T

c

Xiapex Summary of Product Characteristics, November 2013

d

Collagenase Clostridium histolyticum in patients with Dupuytren’s contracture: results from POINT X,

J Hand Surg Eur Vol published online 26 January 2014  

Huard, A. Seghouani, P. P. Szczypa and on behalf of the POINT X Investigators

D. Warwick, M. Arner, G. Pajardi, B. Reichert, Z. Szabo, E. H. Masmejean, J. Fores, D. S. Chapman, R. A. Gerber, F.

an open-label study of clinical and patient-reported outcomes Collagenase Clostridium histolyticum in patients with Dupuytren’s contracture: results from POINT X,

Date of preparation: September 2014 Job Bag Code: SOBIUK/XIA/2014/0037


SPECIAL REPORT: MANAGING DUPUYTREN’S CONTRACTURE

Notes:

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Primary Care – Special Report on Managing Dupuytren’s Contracture