Causes of Dupuytren's Contracture of the Right Hand
Dupuytren's contracture is primarily caused by genetic factors, with environmental influences playing a secondary role in its development and progression.
Primary Causes
Genetic Factors
- Dupuytren's contracture has a strong genetic predisposition and is considered the most frequent genetic disorder of connective tissues 1
- Family history is the strongest influence on age at first surgical intervention, with affected individuals having surgery approximately 5.2 years earlier than those without family history 1
- The percentage of familial cases decreases with age of onset, from 55% in patients aged 40-49 years to 17% in those 80 years or older 1
- The disease shows highest prevalence among Northern European descendants but is widespread globally with varying prevalence 2
- Genetic variants primarily affect the Wnt signaling pathway, with most reported variants found in European/Caucasian subjects 2
Pathophysiological Mechanisms
- The condition involves fibroproliferative changes in the palmar fascia leading to nodule and cord formation 3
- Microvessel narrowing causes localized ischemia, which triggers a cascade of pathological events 4
- During ischemia, ATP converts to hypoxanthine and xanthine, while endothelial xanthine dehydrogenase converts to xanthine oxidase 4
- This process generates oxygen free radicals (superoxide, hydrogen peroxide, hydroxyl radicals) that damage surrounding tissue and stimulate fibroblast proliferation 4
- Proliferating fibroblasts deposit and contract collagen along stress lines, creating a positive feedback loop that explains the progressive nature of the condition 4
- Abnormal build-up of type III collagen is characteristic of the disease 2
- Myofibroblasts abnormally infiltrate the connective tissue and deposit collagen and other extracellular matrix proteins 5
Secondary Contributing Factors
Environmental Risk Factors
- Alcohol consumption is significantly associated with Dupuytren's contracture and may accelerate the disease process by mediating the conversion of xanthine dehydrogenase to xanthine oxidase 4, 6
- Cigarette smoking has been identified as a risk factor 1
- Diabetes is associated with increased risk of developing the condition 4, 1
- Other medical conditions linked to Dupuytren's contracture include hypertension and epilepsy 1
Demographic Factors
- Male sex is the second strongest influence (after family history) on early onset of the disease 1
- The condition predominantly affects elderly male Caucasians 4
- HIV infection has been associated with Dupuytren's contracture 4
Clinical Manifestations
- Progressive fibrosis of the palmar fascia leads to flexion contractures of the affected fingers 3
- The condition impairs daily activities such as typing, performing fine motor tasks, and social interactions like handshaking 3
- Dupuytren's contracture is characterized by the formation of nodules and cords in the palmar fascia 3, 5
- The disease can be identified during physical examination by looking for specific features like Dupuytren's contracture alongside other physical findings such as parotid enlargement 6
Treatment Considerations
- Treatment options include needle aponeurotomy, collagenase Clostridium histolyticum injections with digit manipulation, and surgical fasciectomy 3
- The use of collagenase Clostridium histolyticum has increased over the past decade 3
- Treatment should be considered when the condition begins to impair daily function and quality of life 3
Clinical Pearls and Pitfalls
- Dupuytren's contracture may be confused with other causes of hand contractures such as those seen in certain neuromuscular disorders 6
- The presence of Dupuytren's contracture in a patient with liver disease may suggest alcoholic liver disease, as it's more commonly observed in this condition than in non-alcoholic liver disease 6
- The condition should be distinguished from contractures caused by neurological conditions, which typically have different presentations and associated symptoms 6