Dupuytren’s Disease Murali Krishnan Hand Term - April 2007

Overview Who is Dupuytren? Definition of Dupuytren disease Anatomy of the bands and cords Aetiology and pathopysiology Recurrence Clinical assessment Treatment options

Introduction BARON GUILLAUME DUPUYTREN ( ) “ First among surgeons, Last among men"

Definition Dupuytren’s disease is an abnormal thickening of the fascial tissue resulting in digital flexion contractures. Cell Responsible - Myofibroblast

Anatomy Bands – Normal tissue Cords – Abnormal tissue

Fascias -Thenar aponeurosis -Ulnar aponeurosis -Palmar aponeurosis -Palmodigital fascia (entraps digital nerve) -Digital fascia

Palmar fascia - Longitudinal - Transverse - Vertical

Palmar fascia

Palmodigital fascia and bands

Spiral band and cord

Spiral cord and Nerve

Digital band and cord Digital cord - Central - Lateral

Anatomy

Pretendinous cord causes MCPJ contractures

Anatomy Central and Spiral cords causes PIPJ contracture

Anatomy Superficial transverse ligament is not involved in the disease process Natatory ligament causes web space contractures. In the index finger, Natatory ligament becomes the distal Commisural ligament and causes contracture between the index finger & thumb.

Anatomy Cleland's ligament is not involved in Dupuytren's. Grayson's ligament contributes to the spiral cord. The spiral cord pushes the NVB toward the skin & midline of the finger.

Summary

Pathogenesis

Myofibroblast Responsible for contracture Metaplasia of fibroblast into myofibroblast Features of smooth muscle cell and fibroblast Contains actin microfilaments

Similar fibromatosis Garrods pads Ledderhose disease -5% Peyronies disease -3%

Associated conditions 1.Epilepsy (42%) 2.Alcohol-induced liver disease 3.Diabetes mellitus 4.COAD 5.Hypertension 6.IHD

Influencing factors Genetics Trauma Ischaemia Alcohol Phenobarbitone MMPs and TIMPs Reduced apoptosis Free radicals Interleukin 1

Genetics Common among Caucasian (Scottish) –Curse of Mac Crimmons Rare in Africans and Middle Eastern descent Male predominance

Trauma Micro ruptures in palmar fascia triggers IL-1 Vasomotor disturbance following swelling in hand causing secondary Ischaemia

Ischaemia Adenosine Triphosphate Xanthine dehydrogenase (ATP) Hypoxanthine Xanthine Oxidase Xanthine & Uric Acid Oxidation Free Radicals

Ischaemia Increase in free radicals Decrease in antioxidant enzyme activity Microangiopathy with narrow vessels are found in dupuytren tissue

Alcohol Conversion of Xanthine dehydrogenase to Xanthine oxidase Increases in free radicals Increase in Lysophospatidic acid (LPA) Increases intracellular calcium aiding contracture

Phenobarbitone Increase in Lysophospatidic acid (LPA) Increases intracellular calcium aiding contracture

MMPs and TIMPs Normal levels of MMPs Increased levels of TIMPs-1 Abnormally low MMP : TIMPs ratio –External fixator to improve contraction prior to surgery is said to increase the level of MMPs

Reduced Apoptosis IL 1 and TGF beta reduces the apoptosis of damaged and inflamed cells

Free radicals Fibroblast proliferation 6 fold increase in cords 40 fold increase in nodule Increased production of IL-1 Indirect increase in collagen III

Collagen Normal palmar fascia Predominantly type I collagen Lesser extent type III collagen Dupuytren fascia Increased ratio of type III to type I collagen

IL-1 Fibroblast proliferation Stimulates platelets and macrophages to produce various growth factors (TGF beta) Reduces apoptosis Stimulates langerhans cells of the epidermis Extrinsic pathway: Migration to dermo-epidermal junction – initiates events – contractures

Pathogenesis Mechanisms IntrinsicExtrinsic TGF beta induces Langerhans cells the differentiation pathway of fibroblasts into myofibroblasts

Mechanism IntrinsicExtrinsic

Final contraction Myosin triggered by LPA Contraction of Intracellular actin microfilaments Dupuytren contracture

Stages Proliferative large myofibroblasts very vascular Involution Dense network of myofibroblasts Increased ratio of type III to type I collagen Residual Myofibroblasts disappear Predominantly fibrocytes

Recurrence/Aggressive 1.Young 2. Male 3. Family history 4. Bilateral 5. Fibromatosis elsewhere 6.Garrod's knuckle pads

Future 1.BMP 2.Gene therapy 3.Nitric oxide

Summary Associated conditions Various pathways Role of Free radicals, Interleukin etc Collagen I replaced by collagen III Intrinsic and extrinsic theories Contracture formation Stages

Thank you