<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Duchenne muscular dystrophy and can you explain it in depth? [/INST] Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis followed by the arms. This can result in trouble standing up. Most are unable to walk by the age of 12. Affected muscles may look larger due to increased fat content. Scoliosis is also common. Some may have intellectual disability. Females with a single copy of the defective gene may show mild symptoms.The disorder is X-linked recessive. About two thirds of cases are inherited from a persons mother, while one third of cases are due to a new mutation. It is caused by a mutation in the gene for the protein dystrophin. Dystrophin is important to maintain the muscle fibers cell membrane. Genetic testing can often make the diagnosis at birth. Those affected also have a high level of creatine kinase in their blood.Although there is no known cure, physical therapy, braces, and corrective surgery may help with some symptoms. Assisted ventilation may be required in those with weakness of breathing muscles. Medications used include steroids to slow muscle degeneration, anticonvulsants to control seizures and some muscle activity, and immunosuppressants to delay damage to dying muscle cells. Gene therapy, as a treatment, is in the early stages of study in humans. A small initial study using gene therapy has given some children improved muscle strength, but long term effects are unknown as of 2020.DMD affects about one in 3,500 to 6,000 males at birth. It is the most common type of muscular dystrophy. The life expectancy is 26; however, with excellent care, some may live into their 30s or 40s. The disease is much more rare in girls, occurring approximately once in 50,000,000 live female births.

Signs and symptoms
DMD causes progressive muscle weakness due to muscle fiber disarray, death, and replacement with connective tissue or fat. The voluntary muscles are affected first, especially those of the hips, pelvic area, thighs, calves. It eventually progresses to the shoulders and neck, followed by arms, respiratory muscles, and other areas. Fatigue is common.Signs usually appear before age five, and may even be observed from the moment a boy takes his first steps. There is general difficulty with motor skills, which can result in an awkward manner of walking, stepping, or running. They tend to walk on their toes, in part due to shortening of the Achilles tendon, and because it compensates for knee extensor weakness. Falls can be frequent. It becomes harder and harder for the boy to walk; his ability to walk usually completely disintegrates before age 13. Most men affected with DMD become essentially "paralyzed from the neck down" by the age of 21. Cardiomyopathy, particularly dilated cardiomyopathy, is common, seen in half of 18-year-olds. The development of congestive heart failure or arrhythmia (irregular heartbeat) is only occasional. In late stages of the disease, respiratory impairment and swallowing impairment can occur, which can result in pneumonia.

A classic sign of DMD is trouble getting up from lying or sitting position, as manifested by a positive Gowerss sign. When a child tries to arise from lying on his stomach, he compensates for pelvic muscle weakness through use of the upper extremities: first by rising to stand on his arms and knees, and then "walking" his hands up his legs to stand upright. Another characteristic sign of DMD is pseudohypertrophy (enlarging) of the muscles of the tongue, calves, buttocks, and shoulders (around age 4 or 5). The muscle tissue is eventually replaced by fat and connective tissue, hence the term pseudohypertrophy. Muscle fiber deformities and muscle contractures of Achilles tendon and hamstrings can occur, which impair functionality because the muscle fibers shorten and fibrose in connective tissue. Skeletal deformities can occur, such as lumbar hyperlordosis, scoliosis, anterior pelvic tilt, and chest deformities. Lumbar hyperlordosis is thought to be compensatory mechanism in response to gluteal and quadriceps muscle weakness, all of which cause altered posture and gait (e.g.: restricted hip extension).Non musculoskeletal manifestations of DMD occur. There is a higher risk of neurobehavioral disorders (e.g., ADHD), learning disorders (dyslexia), and non-progressive weaknesses in specific cognitive skills (in particular short-term verbal memory), which are believed to be the result of absent or dysfunctional dystrophin in the brain.

Cause
DMD is caused by a mutation of the dystrophin gene, located on the short arm of the X chromosome (locus Xp21) that codes for dystrophin protein. Mutations can either be inherited or occur spontaneously during germline transmission, causing to a large reduction or absence of dystrophin, a protein that provides structural integrity in muscle cells. Dystrophin is responsible for connecting the actin cytoskeleton of each muscle fiber to the underlying basal lamina (extracellular matrix), through a protein complex containing many subunits. The absence of dystrophin permits excess calcium to penetrate the sarcolemma (the cell membrane). Alterations in calcium and signalling pathways cause water to enter into the mitochondria, which then burst.In skeletal muscle dystrophy, mitochondrial dysfunction gives rise to an amplification of stress-induced cytosolic calcium signals and an amplification of stress-induced reactive-oxygen species production. In a complex cascading process that involves several pathways and is not clearly understood, increased oxidative stress within the cell damages the sarcolemma and eventually results in the death of the cell. Muscle fibers undergo necrosis and are ultimately replaced with adipose and connective tissue.

DMD is inherited in an X-linked recessive pattern. Females typically are carriers of the genetic trait while males are affected. A female carrier will be unaware she carries a mutation until she has an affected son. The son of a carrier mother has a 50% chance of inheriting the defective gene from his mother. The daughter of a carrier mother has a 50% chance of being a carrier and a 50% chance of having two normal copies of the gene. In all cases, an unaffected father either passes a normal Y to his son or a normal X to his daughter. Female carriers of an X-linked recessive condition, such as DMD, can show symptoms depending on their pattern of X-inactivation.DMD is extremely rare in females (about 1 in 50,000,000 female births). It can occur in females with an affected father and a carrier mother, in those who are missing an X chromosome, or those who have an inactivated X chromosome (the most common of the rare reasons). The daughter of a carrier mother and an affected father will be affected or a carrier with equal probability, as she will always inherit the affected X-chromosome from her father and has a 50% chance of also inheriting the affected X-chromosome from her mother.Disruption of the blood-brain barrier has been seen to be a noted feature in the development of DMD.

Diagnosis
Genetic counseling is advised for people with a family history of the disorder. DMD can be detected with about 95% accuracy by genetic studies performed during pregnancy. Creatine kinase (CPK-MM) levels in the bloodstream are extremely high. An electromyography (EMG) shows that weakness is caused by destruction of muscle tissue rather than by damage to nerves.

DNA test
The muscle-specific isoform of the dystrophin gene is composed of 79 exons, and DNA testing (blood test) and analysis can usually identify the specific type of mutation of the exon or exons that are affected. DNA testing confirms the diagnosis in most cases.

Muscle biopsy
If DNA testing fails to find the mutation, a muscle biopsy test may be performed. A small sample of muscle tissue is extracted using a biopsy needle. The key tests performed on the biopsy sample for DMD are immunohistochemistry, immunocytochemistry, and immunoblotting for dystrophin, and should be interpreted by an experienced neuromuscular pathologist. These tests provide information on the presence or absence of the protein. Absence of the protein is a positive test for DMD. Where dystrophin is present, the tests indicate the amount and molecular size of dystrophin, helping to distinguish DMD from milder dystrophinopathy phenotypes. Over the past several years, DNA tests have been developed that detect more of the many mutations that cause the condition, and muscle biopsy is not required as often to confirm the presence of DMD.

Prenatal tests
A prenatal test can be considered when the mother is a known or suspected carrier.Prenatal tests can tell whether the unborn child has one of the most common mutations. Many mutations are responsible for DMD, and some have not been identified, so genetic testing may be falsely negative if the suspected mutation in the mother has not been identified.Prior to invasive testing, determination of the fetal sex is important; while males are sometimes affected by this X-linked disease, female DMD is extremely rare. This can be achieved by ultrasound scan at 16 weeks or more recently by free fetal DNA (cffDNA) testing. Chorion villus sampling (CVS) can be done at 11–14 weeks, and has a 1% risk of miscarriage. Amniocentesis can be done after 15 weeks, and has a 0.5% risk of miscarriage. Non invasive prenatal testing can be done around 10–12 weeks. Another option in the case of unclear genetic test results is fetal muscle biopsy.

Treatment
No cure for DMD is known, and an ongoing medical need has been recognized by regulatory authorities. Gene therapy has shown some success.Treatment is generally aimed at controlling symptoms to maximize the quality of life which can be measured using specific questionnaires, and include:

Corticosteroids such as prednisolone and deflazacort lead to short-term improvements in muscle strength and function up to 2 years. Corticosteroids have also been reported to help prolong walking, though the evidence for this is not robust.
Randomised control trials have shown that β2 agonists increase muscle strength, but do not modify disease progression. Follow-up time for most RCTs on β2 agonists is only around 12 months, hence results cannot be extrapolated beyond that time frame.
Mild, nonjarring physical activity such as swimming is encouraged. Inactivity (such as bed rest) can worsen the muscle disease.
Physical therapy is helpful to maintain muscle strength, flexibility, and function.
Orthopedic appliances (such as braces and wheelchairs) may improve mobility and the ability for self-care. Form-fitting removable leg braces that hold the ankle in place during sleep can defer the onset of contractures.
Appropriate respiratory support as the disease progresses is important.
Cardiac problems may require a pacemaker.The medication eteplirsen, a Morpholino antisense oligo, has been approved in the United States for the treatment of mutations amenable to dystrophin exon 51 skipping. The US approval has been controversial as eteplirsen failed to establish a clinical benefit; it has been refused approval by the European Medicines Agency.The medication ataluren (Translarna) is approved use in the European Union.The antisense oligonucleotide golodirsen (Vyondys 53) was approved for medical use in the United States in 2019, for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript.The Morpholino antisense oligonucleotide viltolarsen (Viltepso) was approved for medical use in the United States in August 2020, for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. It is the second approved targeted treatment for people with this type of mutation in the United States. Approximately 8% of people with DMD have a mutation that is amenable to exon 53 skipping.Casimersen was approved for medical use in the United States in February 2021, and it is the first FDA-approved targeted treatment for people who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.Comprehensive multidisciplinary care guidelines for DMD have been developed by the Centers for Disease Control and Prevention, and were published in two parts in The Lancet Neurology in 2010. An update was published in 2018.

Physical therapy
Physical therapists are concerned with enabling patients to reach their maximum physical potential. Their aim is to:
minimize the development of contractures and deformity by developing a programme of stretches and exercises where appropriate
anticipate and minimize other secondary complications of a physical nature by recommending bracing and durable medical equipment
monitor respiratory function and advise on techniques to assist with breathing exercises and methods of clearing secretions

Respiration assistance
Modern "volume ventilators/respirators", which deliver an adjustable volume (amount) of air to the person with each breath, are valuable in the treatment of people with muscular dystrophy-related respiratory problems. The ventilator may require an invasive endotracheal or tracheotomy tube through which air is directly delivered, but for some people, noninvasive delivery through a face mask or mouthpiece is sufficient. Positive airway pressure machines, particularly bilevel ones, are sometimes used in this latter way. The respiratory equipment may easily fit on a ventilator tray on the bottom or back of a power wheelchair with an external battery for portability.Ventilator treatment may start in the mid- to late teens when the respiratory muscles can begin to collapse. If the vital capacity has dropped below 40% of normal, a volume ventilator/respirator may be used during sleeping hours, a time when the person is most likely to be underventilating (hypoventilating). Hypoventilation during sleep is determined by a thorough history of sleep disorder with an oximetry study and a capillary blood gas (see pulmonary function testing).
A cough assist device can help with excess mucus in lungs by hyperinflation of the lungs with positive air pressure, then negative pressure to get the mucus up. If the vital capacity continues to decline to less than 30 percent of normal, a volume ventilator/respirator may also be needed during the day for more assistance. The person gradually will increase the amount of time using the ventilator/respirator during the day as needed. However, there are also people with the disease in their 20s who have no need for a ventilator.

Future developments
There is no cure for any of the muscular dystrophies. Several drugs designed to address the root cause are under development, including gene therapy (Microdystrophin), and antisense drugs (Ataluren, Eteplirsen etc.). Other medications used include corticosteroids (Deflazacort), calcium channel blockers (Diltiazem) to slow skeletal and cardiac muscle degeneration, anticonvulsants to control seizures and some muscle activity, and immunosuppressants (Vamorolone) to delay damage to dying muscle cells. Physical therapy, braces, and corrective surgery may help with some symptoms while assisted ventilation may be required in those with weakness of breathing muscles. Outcomes depend on the specific type of disorder.A paper published by Stanford University on 10 March 2022 demonstrated that patients with muscular dystrophies could benefit from new therapies targeting the specific pathways contributing directly to muscle disorders. Three recent advances are likely to enhance the landscape of treatments for muscular dystrophies such as DMD. First, induced pluripotent stem cells (iPSCs) allow researchers to design effective treatment strategies. Second, artificial intelligence (AI) can help identify therapeutic targets. Third, a high volume of multi-omics data gathered from diverse sources through disease models can provide valuable information about converging and diverging pathways.

Prognosis
Duchenne muscular dystrophy is a rare progressive disease which eventually affects all voluntary muscles and involves the heart and breathing muscles in later stages. Life expectancy is estimated to be around 25–26, but this varies. With excellent medical care, affected men often live into their 30s. David Hatch of Paris, Maine, may be the oldest person in the world with the disease; as of 2021, he was 58.The most common direct cause of death in people with DMD is respiratory failure. Complications from treatment, such as mechanical ventilation and tracheotomy procedures, are also a concern. The next leading cause of death is cardiac-related conditions such as heart failure brought on by dilated cardiomyopathy. With respiratory assistance, the median survival age can reach up to 40. In rare cases, people with DMD have been seen to survive into their forties or early fifties, with proper positioning in wheelchairs and beds, and the use of ventilator support (via tracheostomy or mouthpiece), airway clearance, and heart medications. Early planning of the required supports for later-life care has shown greater longevity for people with DMD.Curiously, in the mdx mouse model of Duchenne muscular dystrophy, the lack of dystrophin is associated with increased calcium levels and skeletal muscle myonecrosis. The intrinsic laryngeal muscles (ILMs) are protected and do not undergo myonecrosis. ILMs have a calcium regulation system profile suggestive of a better ability to handle calcium changes in comparison to other muscles, and this may provide a mechanistic insight for their unique pathophysiological properties. The ILM may facilitate the development of novel strategies for the prevention and treatment of muscle wasting in a variety of clinical scenarios. In addition, patients with Duchenne muscular dystrophy also have elevated plasma lipoprotein levels, implying a primary state of dyslipidemia in patients.

Epidemiology
DMD is the most common type of muscular dystrophy; it affects about one in 5,000 males at birth. DMD has an incidence of one in 3,600 male infants.In the US, a 2010 study showed a higher amount of those with DMD age ranging from 5 to 54 who are Hispanic compared to non-Hispanic Whites, and non-Hispanic Blacks.

History
The disease was first described by the Neapolitan physician Giovanni Semmola in 1834 and Gaetano Conte in 1836. However, DMD is named after the French neurologist Guillaume-Benjamin-Amand Duchenne (1806–1875), who in the 1861 edition of his book Paraplegie hypertrophique de lenfance de cause cerebrale, described and detailed the case of a boy who had this condition. A year later, he presented photos of his patient in his Album de photographies pathologiques. In 1868, he gave an account of 13 other affected children. Duchenne was the first to do a biopsy to obtain tissue from a living patient for microscopic examination.

Notable cases
Alfredo ("Dino", "Alfredino") Ferrari (born January 1932 in Modena), the son of Enzo Ferrari, designed the 1.5 L DOHC V6 engine for the model F2 at the end of 1955.  But Dino never saw the engine produced:  he died on 30 June 1956 in Modena at the age of 24, before his namesakes Dino and Fiat Dino were made.Rapper Darius Weems had the disease and used his notoriety to raise awareness and funds for treatment.  He died at the age of 27 (his brother also had the disease, until his death at the age of 19). The film Darius Goes West documents Weemss journey of growth and acceptance of having the disease.Jonathan Evisons novel, The Revised Fundamentals of Caregiving, published in 2012, depicted a young man affected by the disease.  In 2016, Netflix released The Fundamentals of Caring, a film based on the novel.

Research
Current research includes exon-skipping, stem cell replacement therapy, analog up-regulation, gene replacement, and supportive care to slow disease progression.Efforts are ongoing to find medications that either return the ability to make dystrophin or utrophin. Other efforts include trying to block the entry of calcium ions into muscle cells.

Exon-skipping
Antisense oligonucleotides (oligos), structural analogs of DNA, are the basis of a potential treatment for 10% of people with DMD. The compounds allow faulty parts of the dystrophin gene to be skipped when it is transcribed to RNA for protein production, permitting a still-truncated but more functional version of the protein to be produced. It is also known as nonsense suppression therapy.Two kinds of antisense oligos, 2-O-methyl phosphorothioate oligos (like drisapersen) and Morpholino oligos (like eteplirsen), have tentative evidence of benefit and are being studied. Eteplirsen is targeted to skip exon 51.  "As an example, skipping exon 51 restores the reading frame of ~ 15% of all the boys with deletions. It has been suggested that by having 10 AONs to skip 10 different exons it would be possible to deal with more than 70% of all DMD boys with deletions." This represents about 1.5% of cases.

People with Beckers muscular dystrophy, which is milder than DMD, have a form of dystrophin which is functional even though it is shorter than normal dystrophin. In 1990 England et al. noticed that a patient with mild Becker muscular dystrophy was lacking 46% of his coding region for dystrophin. This functional, yet truncated, form of dystrophin gave rise to the notion that shorter dystrophin can still be therapeutically beneficial. Concurrently, Kole et al. had modified splicing by targeting pre-mRNA with antisense oligonucleotides (AONs). Kole demonstrated success using splice-targeted AONs to correct missplicing in cells removed from beta-thalassemia patients Wiltons group tested exon skipping for muscular dystrophy.

Gene therapy
Researchers are working on a gene editing method to correct a mutation that leads to Duchenne muscular dystrophy (DMD). Researchers used a technique called CRISPR/Cas9-mediated genome editing, which can precisely remove a mutation in the dystrophin gene in DNA, allowing the bodys DNA repair mechanisms to replace it with a normal copy of the gene. The benefit of this over other gene therapy techniques is that it can permanently correct the "defect" in a gene rather than just transiently adding a "functional" one.Genome editing through the CRISPR/Cas9 system is not currently feasible in humans. However, it may be possible, through advancements in technology, to use this technique to develop therapies for DMD in the future. In 2007, researchers did the worlds first clinical (viral-mediated) gene therapy trial for Duchenne MD.Biostrophin is a delivery vector for gene therapy in the treatment of Duchenne muscular dystrophy and Becker muscular dystrophy.

References
Further reading
Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D,  et al. (March 2018). "Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management". Lancet Neurol. 17 (3): 251–267 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Dupuytrens contracture and can you explain it in depth? [/INST] Dupuytrens contracture (also called Dupuytrens disease, Morbus Dupuytren, Viking disease, palmar fibromatosis and Celtic hand) is a condition in which one or more fingers become progressively bent in a flexed position. It is named after Guillaume Dupuytren, who first described the underlying mechanism of action, followed by the first successful operation in 1831 and publication of the results in The Lancet in 1834. It usually begins as small, hard nodules just under the skin of the palm, then worsens over time until the fingers can no longer be fully straightened. While typically not painful, some aching or itching may be present. The ring finger followed by the little and middle fingers are most commonly affected. It can affect one or both hands. The condition can interfere with activities such as preparing food, writing, putting your hand in a tight pocket, putting on gloves, or shaking hands.The cause is unknown but might have a genetic component. Risk factors include family history, alcoholism, smoking, thyroid problems, liver disease, diabetes, previous hand trauma, and epilepsy. The underlying mechanism involves the formation of abnormal connective tissue within the palmar fascia. Diagnosis is usually based on a physical exam. Blood tests or imaging studies are not usually necessary.Initial treatment is typically with a cortisone shot into the affected area, occupational therapy, and physical therapy. Among those who worsen, clostridial collagenase injections or surgery may be tried. While radiation therapy is used to treat this condition, the evidence for this use is scarce. The Royal College of Radiologists (RCR) Faculty of Clinical Oncology concluded that radiotherapy is effective in early stage disease which has progressed within the last 6 to 12 months. The condition may recur despite treatment. If it does return after treatment, it can be treated again with further improvement. It is easier to treat when the amount of finger bending is more mild.It was once believed that Dupuytrens most often occurs in white males over the age of 50  and is rare among Asians and Africans. It sometimes was erroneously called "Viking disease," since it was often recorded among those of Nordic descent. In Norway, about 30% of men over 60 years old have the condition, while in the United States about 5% of people are affected at some point in time. In the United Kingdom, about 20% of people over 65 have some form of the disease.More recent and wider studies show the highest prevalence in Africa (17 per cent), Asia (15 per cent).

Signs and symptoms
Typically, Dupuytrens contracture first presents as a thickening or nodule in the palm, which initially can be with or without pain. Later in the disease process, which can be years later, there is painless increasing loss of range of motion of the affected finger(s). The earliest sign of a contracture is a triangular "puckering" of the skin of the palm as it passes over the flexor tendon just before the flexor crease of the finger, at the metacarpophalangeal (MCP) joint.Generally, the cords or contractures are painless, but, rarely, tenosynovitis can occur and produce pain. The most common finger to be affected is the ring finger; the thumb and index finger are much less often affected. The disease begins in the palm and moves towards the fingers, with the metacarpophalangeal (MCP) joints affected before the proximal interphalangeal (PIP) joints. The MCP joints at the base of the finger responds much better to treatment and are usually able to fully extend after treatment. Due to anatomic differences in the ligaments and extensor tendons at the PIP joints, they may have some residual flexion. Proper patient education is necessary to set realistic treatment expectation.
In Dupuytrens contracture, the palmar fascia within the hand becomes abnormally thick, which can cause the fingers to curl and can impair finger function. The main function of the palmar fascia is to increase grip strength; thus, over time, Dupuytrens contracture decreases a persons ability to hold objects and use the hand in many different activities. Dupuytrens contracture can also be experienced as embarrassing in social situations and can affect quality of life People may report pain, aching, and itching with the contractions. Normally, the palmar fascia consists of collagen type I, but in Dupuytren patients, the collagen changes to collagen type III, which is significantly thicker than collagen type I.

Related conditions
People with severe involvement often show lumps on the back of their finger joints (called "Garrods pads", "knuckle pads", or "dorsal Dupuytren nodules"), and lumps in the arch of the feet (plantar fibromatosis or Ledderhose disease). In severe cases, the area where the palm meets the wrist may develop lumps. It is thought the condition Peyronies disease is related to Dupuytrens contracture.

Risk factors
Dupuytrens contracture is a non-specific condition, but primarily affects:

Non-modifiable
People of Scandinavian or Northern European ancestry; it has been called the "Viking disease", though it is also widespread in some Mediterranean countries, e.g., Spain and Bosnia. Dupuytrens is unusual among groups such as Chinese and Africans.
Men rather than women; men are more likely to develop the condition (80%)
People over the age of 50 (5% to 15% of men in that group in the US); the likelihood of getting Dupuytrens disease increases with age
People with a family history (60% to 70% of those affected have a genetic predisposition to Dupuytrens contracture)

Modifiable
Smokers, especially those who smoke 25 cigarettes or more a day
Thinner people, i.e., those with a lower-than-average body mass index.
Manual workers
Alcoholics

Other conditions
People with a higher-than-average fasting blood glucose level
People with previous hand injury
People with Ledderhose disease (plantar fibromatosis)
People with epilepsy (possibly due to anti-convulsive medication)
People with diabetes mellitus
People with HIV
Previous myocardial infarctionIn one study, those with stage 2 of the disease were found to have a slightly increased risk of mortality, especially from cancer.

Diagnosis
Types
According to the American Dupuytrens specialist Dr. Charles Eaton, there may be three types of Dupuytrens disease:
Type 1: A very aggressive form of the disease found in only 3% of people with Dupuytrens, which can affect men under 50 with a family history of Dupuytrens. It is often associated with other symptoms such as knuckle pads and Ledderhose disease. This type is sometimes known as Dupuytrens diathesis.
Type 2: The more normal type of Dupuytrens disease, usually found in the palm only, and which generally begins above the age of 50. According to Eaton, this type may be made more severe by other factors such as diabetes or heavy manual labor.
Type 3: A mild form of Dupuytrens which is common among diabetics or which may also be caused by certain medications, such as the anti-convulsants taken by people with epilepsy. This type does not lead to full contracture of the fingers, and is probably not inherited.

Treatment
Treatment is indicated when the so-called table-top test is positive. With this test, the person places their hand on a table. If the hand lies completely flat on the table, the test is considered negative. If the hand cannot be placed completely flat on the table, leaving a space between the table and a part of the hand as big as the diameter of a ballpoint pen, the test is considered positive and surgery or other treatment may be indicated. Additionally, finger joints may become fixed and rigid. There are several types of treatment, with some hands needing repeated treatment.The main categories listed by the International Dupuytren Society in order of stage of disease are radiation therapy, needle aponeurotomy (NA), collagenase injection, and hand surgery. As of 2016 the evidence on the efficacy of radiation therapy was considered inadequate in quantity and quality, and difficult to interpret because of uncertainty about the natural history of Dupuytrens disease.Needle aponeurotomy is most effective for Stages I and II, covering 6–90 degrees of deformation of the finger. However, it is also used at other stages.
Collagenase injection is likewise most effective for Stages I and II. However, it is also used at other stages.Hand surgery is effective at stage I to stage IV.

Surgery
On 12 June 1831, Dupuytren performed a surgical procedure on a person with contracture of the 4th and 5th digits who had been previously told by other surgeons that the only remedy was cutting the flexor tendons. He described the condition and the operation in The Lancet in 1834 after presenting it in 1833, and posthumously in 1836 in a French publication by Hôtel-Dieu de Paris. The procedure he described was a minimally invasive needle procedure.
Because of high recurrence rates, new surgical techniques were introduced, such as fasciectomy and then dermofasciectomy. Most of the diseased tissue is removed with these procedures.Recurrence rates are low. For some individuals, the partial insertion of "K-wires" into either the DIP or PIP joint of the affected digit for a period of a least 21 days to fuse the joint is the only way to halt the diseases progress. After removal of the wires, the joint is fixed into flexion, which is considered preferable to fusion at extension.
In extreme cases, amputation of fingers may be needed for severe or recurrent cases or after surgical complications.

Limited fasciectomy
Limited/selective fasciectomy removes the pathological tissue, and is a common approach. Low-quality evidence suggests that fasciectomy may be more effective for people with advanced Dupuytrens contractures.During the procedure, the person is under regional or general anesthesia. A surgical tourniquet prevents blood flow to the limb. The skin is often opened with a zig-zag incision but straight incisions with or without Z-plasty are also described and may reduce damage to neurovascular bundles. All diseased cords and fascia are excised. The excision has to be very precise to spare the neurovascular bundles. Because not all the diseased tissue is visible macroscopically, complete excision is uncertain.A 20-year review of surgical complications associated with fasciectomy showed that major complications occurred in 15.7% of cases, including digital nerve injury (3.4%), digital artery injury (2%), infection (2.4%), hematoma (2.1%), and complex regional pain syndrome (5.5%), in addition to minor complications including painful flare reactions in 9.9% of cases and wound healing complications in 22.9% of cases. After the tissue is removed the incision is closed. In the case of a shortage of skin, the transverse part of the zig-zag incision is left open. Stitches are removed 10 days after surgery.After surgery, the hand is wrapped in a light compressive bandage for one week. Flexion and extension of the fingers can start as soon as the anaesthesia has resolved. It is common to experience tingling within the first week after surgery. Hand therapy is often recommended. Approximately 6 weeks after surgery the patient is able completely to use the hand.The average recurrence rate is 39% after a fasciectomy after a median interval of about 4 years.

Wide-awake fasciectomy
Limited/selective fasciectomy under local anesthesia (LA) with epinephrine but no tourniquet is possible. In 2005, Denkler described the technique.

Dermofasciectomy
Dermofasciectomy is a surgical procedure that may be used when:

The skin is clinically involved (pits, tethering, deficiency, etc.)
The risk of recurrence is high and the skin appears uninvolved (subclinical skin involvement occurs in ~50% of cases)
Recurrent disease. Similar to a limited fasciectomy, the dermofasciectomy removes diseased cords, fascia, and the overlying skin.Typically, the excised skin is replaced with a skin graft, usually full thickness, consisting of the epidermis and the entire dermis. In most cases the graft is taken from the antecubital fossa (the crease of skin at the elbow joint) or the inner side of the upper arm. This place is chosen because the skin color best matches the palms skin color. The skin on the inner side of the upper arm is thin and has enough skin to supply a full-thickness graft. The donor site can be closed with a direct suture.The graft is sutured to the skin surrounding the wound. For one week the hand is protected with a dressing. The hand and arm are elevated with a sling. The dressing is then removed and careful mobilization can be started, gradually increasing in intensity. After this procedure the risk of recurrence is minimised, but Dupuytrens can recur in the skin graft and complications from surgery may occur.

Segmental fasciectomy with/without cellulose
Segmental fasciectomy involves excising part(s) of the contracted cord so that it disappears or no longer contracts the finger. It is less invasive than the limited fasciectomy, because not all the diseased tissue is excised and the skin incisions are smaller.The person is placed under regional anesthesia and a surgical tourniquet is used. The skin is opened with small curved incisions over the diseased tissue. If necessary, incisions are made in the fingers. Pieces of cord and fascia of approximately one centimeter are excised. The cords are placed under maximum tension while they are cut. A scalpel is used to separate the tissues. The surgeon keeps removing small parts until the finger can fully extend. The person is encouraged to start moving his or her hand the day after surgery. They wear an extension splint for two to three weeks, except during physical therapy.The same procedure is used in the segmental fasciectomy with cellulose implant. After the excision and a careful hemostasis, the cellulose implant is placed in a single layer in between the remaining parts of the cord.After surgery people wear a light pressure dressing for four days, followed by an extension splint. The splint is worn continuously during nighttime for eight weeks. During the first weeks after surgery the splint may be worn during daytime.

Less invasive treatments
Studies have been conducted for percutaneous release, extensive percutaneous aponeurotomy with lipografting and collagenase. These treatments show promise.

Percutaneous needle fasciotomy
Needle aponeurotomy is a minimally-invasive technique where the cords are weakened through the insertion and manipulation of a small needle. The cord is sectioned at as many levels as possible in the palm and fingers, depending on the location and extent of the disease, using a 25-gauge needle mounted on a 10 ml syringe. Once weakened, the offending cords can be snapped by putting tension on the finger(s) and pulling the finger(s) straight. After the treatment a small dressing is applied for 24 hours, after which people are able to use their hands normally. No splints or physiotherapy are given.The advantage of needle aponeurotomy is the minimal intervention without incision (done in the office under local anesthesia) and the very rapid return to normal activities without need for rehabilitation, but the nodules may resume growing. A study reported postoperative gain is greater at the MCP-joint level than at the level of the IP-joint and found a reoperation rate of 24%; complications are scarce. Needle aponeurotomy may be performed on fingers that are severely bent (stage IV), and not just in early stages. A 2003 study showed 85% recurrence rate after 5 years.A comprehensive review of the results of needle aponeurotomy in 1,013 fingers was performed by Gary M. Pess, MD, Rebecca Pess, DPT, and Rachel Pess, PsyD, and published in the Journal of Hand Surgery April 2012. Minimal follow-up was 3 years. Metacarpophalangeal joint (MP) contractures were corrected at an average of 99% and proximal interphalangeal joint (PIP) contractures at an average of 89% immediately post procedure. At final follow-up, 72% of the correction was maintained for MP joints and 31% for PIP joints. The difference between the final corrections for MP versus PIP joints was statistically significant. When a comparison was performed between people aged 55 years and older versus under 55 years, there was a statistically significant difference at both MP and PIP joints, with greater correction maintained in the older group.Gender differences were not statistically significant. Needle aponeurotomy provided successful correction to 5° or less contracture immediately post procedure in 98% (791) of MP joints and 67% (350) of PIP joints. There was recurrence of 20° or less over the original post-procedure corrected level in 80% (646) of MP joints and 35% (183) of PIP joints. Complications were rare except for skin tears, which occurred in 3.4% (34) of digits. This study showed that NA is a safe procedure that can be performed in an outpatient setting. The complication rate was low, but recurrences were frequent in younger people and for PIP contractures.

Extensive percutaneous aponeurotomy and lipografting
A technique introduced in 2011 is extensive percutaneous aponeurotomy with lipografting. This procedure also uses a needle to cut the cords. The difference with the percutaneous needle fasciotomy is that the cord is cut at many places. The cord is also separated from the skin to make place for the lipograft that is taken from the abdomen or ipsilateral flank. This technique shortens the recovery time. The fat graft results in supple skin.Before the aponeurotomy, a liposuction is done to the abdomen and ipsilateral flank to collect the lipograft. The treatment can be performed under regional or general anesthesia. The digits are placed under maximal extension tension using a firm lead hand retractor. The surgeon makes multiple palmar puncture wounds with small nicks. The tension on the cords is crucial, because tight constricting bands are most susceptible to be cut and torn by the small nicks, whereas the relatively loose neurovascular structures are spared. After the cord is completely cut and separated from the skin the lipograft is injected under the skin. A total of about 5 to 10 ml is injected per ray.After the treatment the person wears an extension splint for 5 to 7 days. Thereafter the person returns to normal activities and is advised to use a night splint for up to 20 weeks.

Collagenase
Clostridial collagenase injections have been found to be more effective than placebo. The cords are weakened through the injection of small amounts of the enzyme collagenase, which breaks peptide bonds in collagen.The treatment with collagenase is different for the MCP joint and the PIP joint. In a MCP joint contracture the needle must be placed at the point of maximum bowstringing of the palpable cord.The needle is placed vertically on the bowstring. The collagenase is distributed across three injection points. For the PIP joint the needle must be placed not more than 4 mm distal to palmar digital crease at 2–3 mm depth. The injection for PIP consists of one injection filled with 0.58 mg CCH 0.20 ml. The needle must be placed horizontal to the cord and also uses a 3-point distribution. After the injection the persons hand is wrapped in bulky gauze dressing and must be elevated for the rest of the day. After 24 hours the person returns for passive digital extension to rupture the cord. Moderate pressure for 10–20 seconds ruptures the cord.After the treatment with collagenase the person should use a night splint and perform digital flexion/extension exercises several times per day for 4 months.In February 2010 the US Food and Drug Administration (FDA) approved injectable collagenase extracted from Clostridium histolyticum for the treatment of Dupuytrens contracture in adults with a palpable Dupuytrens cord. (Three years later, it was approved as well for the treatment of the sometimes related Peyronies disease.) In 2011 its use for the treatment of Dupuytrens contracture was approved as well by the European Medicines Agency, and it received similar approval in Australia in 2013. However, the Swedish manufacturer abruptly withdrew distribution of this drug in Europe and the UK in March 2020 for commercial reasons.(It now is promoted primarily as a dermatological treatment for cellulite aka "cottage cheese thighs"). Collagenase is no longer available on the National Health System except as part of a small clinical trial.

Radiation therapy
Radiation therapy has been used mostly for early-stage disease, but is unproven. Evidence to support its use as of 2017, however, was scarce —efforts to gather evidence are complicated due to a poor understanding of how the condition develops over time. It has only been looked at in early disease. The Royal College of Radiologists concluded that radiotherapy is effective in early stage disease which has progressed within the last 6 to 12 months.

Alternative medicine
Several alternate therapies such as vitamin E treatment have been studied, though without control groups. Most doctors do not value those treatments. None of these treatments stops or cures the condition permanently. A 1949 study of vitamin E therapy found that "In twelve of the thirteen patients there was no evidence whatever of any alteration. ... The treatment has been abandoned."Laser treatment (using red and infrared at low power) was informally discussed in 2013 at an International Dupuytren Society forum, as of which time little or no formal evaluation of the techniques had been completed.

Postoperative care
Postoperative care involves hand therapy and splinting. Hand therapy is prescribed to optimize post-surgical function and to prevent joint stiffness. The extent of hand therapy is depending on the patient and the corrective procedure.Besides hand therapy, many surgeons advise the use of static or dynamic splints after surgery to maintain finger mobility. The splint is used to provide prolonged stretch to the healing tissues and prevent flexion contractures </s>