Dupuytren Literature: Diathesis and Biologic Severity

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  1. Preclinical
  2. Activation (Clinical)
  3. Progression
  4. Correction (Angular)
  5. Recontraction
  6. Stabilization

1. Preclinical: see https://dupuytrens.org/dupuytren-literature-abnormalities-normal-appearing-tissue/

2. Activation: Risk Factors of ever developing Dupuytren-like findings

3. Progression: risk (not rate) of progressing from nodule to contracture

  • Data (mostly) supports relationship:
  • Pseudo-Dupuytren: early cords/nodules without progression
  • Not clear one way or the other impact on risk of progressive contracture
    • In DD patients, knuckle pads are as common in those who have not had surgery as those who have (Mikkelsen 1977).
    • ± Epilepsy (Strong pro and con data – both epilepsy and antiepileptics)
    • ± Peyronie (No data)
    • ± Frozen shoulder (No data)

4. Initial Correction: Exam more predictive than diathesis

  • McFarlane outcome formula to predict early outcome (Legge 1980)
    • Worse with # involved rays, small finger procedure, PIP, ↑ Preop contracture
  • Factors predicting lack of full correction (Adam 1992)
    • Worse: PIP joint, Redo PIP, small finger PIP, more than one ray involved
  • Diathesisis  not predictive of initial outcomes. Post-procedure range of motion, DASH, MHQ scores correlated with unilateral/bilateral involvement, but not with age of onset, ectopic disease, or family history of Dupuytren (Herweijer 2007 ). Age, gender, occupation, alcohol not predictive (Adam 1992) of early outcomes.
  • PIP release worse than only manipulation esp. if pinned (Breed 1996)
  • Incomplete correction more likely for MCP > 50, PIP >40 (Witthaut 2013, Schulze 2014, Verheyden 2014)
  • Procedure: PIP correction more likely with surgery than CCH (Zhou 2015)
  • Joint: PIP correction less likely than MCP correction (Badalamente 2013)

5. Recontraction: Rate of post-treatment re-contracture

  • True vs false recurrence (Dias 2013, Eaton 2015)
    • Early: 1st 6 weeks then plateau: persistent secondary pathoanatomy
    • Progressive: no plateau: persistent biologic activity
    • Late: after a year or more of stability: true recurrence (reactivation)
  • Diathesis factors Predict relative risk of re-contracture. Diathesis doesn’t predict early complications or short-term outcome.
    • Hueston’s original: four factors (Hueston 1961)
      • Any family history, knuckle pads, bilateral, Ledderhose
    • Hindocha score: five factors combined: (only Caucasians studied) (Hindocha 2006B)
      • Independent significance: knuckle pads, male gender, diagnosis age 50 or younger.
      • If combined: Bilateral, parent/sibling family history, knuckle pads, male gender, diagnosis age 50 or younger. Each factor increased 4-year recurrence risk by 10%; having all 5 tripled recurrence rate compared to none.
    • Abe Diathesis score (Abe 2004)
      • 1 point each for bilateral, small finger surgery, onset < 50 y
      • 2 points each for Ledderhose, knuckle pads, thumb / index disease
      • Diathesis score = sum of points. Increased risk for score > 4.
    • Degreef Risk Factors for recurrence (Degreef 2011)
      • Bilateral, ectopic disease, onset < 50 y, > 2 two rays affected, thumb disease, + family history, small finger surgery, male
    • High genetic risk score (WNT4 WNT7B WNT2 RSPO2 MAFB DMRT1 DMRT1 EPDR1) associated with age of onset younger than 50, positive family history, knuckle pads, and Ledderhose (Dolmans 2012)
    • Diathesis lacks universal agreement. For example, Vigroux (Vigroux 1992) reported that contracture severity was predictive of recurrence, but found no significant influence of family history, age of onset, gender, or ectopic disease on recurrence. Jurisic (Jurisic 2008) reported higher recurrence rates for patients older than 50 at the time of diagnosis. The data from a number of studies (Hueston 1963, McFarlane 1990, Foucher 1992, Moermans 1991, Vigroux 1992, Hindocha 2006B) shows no significant correlation between family history and recurrence risk.
  • Age < 60 at time of surgery (Rombouts 1989)
  • Histology of excised tissues
    • Risk: Proliferative > Fibrocellular > Fibrotic (Rombouts 1989)
    • Recurrence rate of proliferative 3X Fibrotic (Balaguer 2009)
    • Independent of Diathesis factors (!) (Balaguer 2009)
    • Cords of more severe contractures less cellular (Verjee 2009)
    • The rock and the hard place: Less severe contractures: more biologically active; recurrence More severe contractures: less biologically active; 2° pathoanatomy
  • Procedure type: Recurrence rate after minimal twice that of fasciectomy (Eaton 2015)
  • Success: higher re-contracture rate with less than full correction (Vigroux 1992, Dias 2006, Peimer 2013)
  • Angle: higher re-contracture rate with greater initial deformity (Dias 2006); higher recurrence rate for pretreatment PIP > 40° (Peimer 2013), MCP > 50° (Peimer 2015)
  • Joint treated: PIP much more rapid than MCP; isolated PIP worse (Crowley 1999)
  • Finger treated: Greater risk small finger (Degreef 2011)
  • Comorbidities: No effect on recurrence: (Hindocha 2006B, Degreef 2011) Smoking, Alcohol, Frozen shoulder, Diabetes, Manual labor, Prior injury

6. Stabilization

  • Mechanisms: Regression (Reilly 2005, Lanting 2016), Stress shielding (Verjee 2009, Melamed 2017)
  • If minimal contracture: Pseudo-Dupuytren
  • If moderate contracture: stress shielding from joint capsule contracture
  • If severe contracture: stress shielding from disuse / functional amputation

Most influential factors Biologic vs. Anatomic

  • Activation: Parent / sibling with disease (Biologic)
  • Progression: Family history, prior contracture (Biologic)
  • Correction: Contracture location / angle (Anatomic)
  • Early Loss of Correction: Residual anatomic factors (Anatomic)
  • Progressive Recontraction: Diathesis, procedure (Both)
  • Prolonged Stabilization: Diathesis, stress shielding (Both)

Additional Points

  • Recontracture is a rate over time, not a fixed risk
  • “Average follow up” duration spanning multiple years is bad data
  • Subset of patients requiring procedures: selection bias – more severe
  • Subset of patients achieving full correction: selection bias – lower recurrence
  • Almost every Dupuytren association is disputed somewhere

Summary of Influences:

Published Factors Influencing Risk of Dupuytren Events Increase       Decrease     No effect     ± Contradictory data     [blank] No data
Events
Factors Diagnosis Progression Partial correction Recontracture Rate
Family History
Caucasian  
Male
↑ Current age
Knuckle pads
Ledderhose
Frozen Shoulder
Peyronie ±    
Diabetes
Genetic Score  
Hyperlipidemia
Psoriasis  
Epilepsy ± ±
Epilepsy meds ± ±
Underweight  
Overweight  
Rheumatoid  
Smoking
Excess Alcohol ±
Manual Labor ±
Local Trauma
 Age of onset
Cm2 area involved
Bilateral
# digits involved
Full correction
 Age at treatment
# prior procedures
PIP procedure
PIP > 40°
MCP > 50°
Ray > 90°
Thumb involvement
CCH / PNF
Small finger procedure
Open PIP release
Proliferative histology
Fibrotic histology

References

  • Abe Y, Rokkaku T, Ebata T, Tokunaga S, Yamada T. (2007). Dupuytren’s Disease Following Acute Injury in Japanese Patients: Dupuytren’s Disease or Not? The Journal of Hand Surgery, European Volume 32 (5): 569–72. (PDF)
  • Abe Y, Rokkaku T, Ofuchi S, Tokunaga S, Takahashi K, Moriya H. (2004). An Objective Method to Evaluate the Risk of Recurrence and Extension of Dupuytren’s Disease. Journal of Hand Surgery (Edinburgh, Scotland) 29 (5): 427–30. (PDF)
  • Adam RF, Loynes RD. (1992). Prognosis in Dupuytren’s Disease. JHS(A) 17 (2): 312–17. (PDF)
  • Akhavani Ma, McMurtrie a, Webb M, Muir L. (2015). A Review of the Classification of Dupuytren’s Disease. Journal of Hand Surgery (European Volume) 40 (2): 155–65. (PDF)
  • Alman Benjamin A, Greel Debra A, Ruby Leonard K, Goldberg Michael J, Wolfe Hubert J. (1996). Regulation of Proliferation and Platelet-Derived Growth Factor Expression in Palmar Fibromatosis (Dupuytren Contracture) by Mechanical Strain. Journal of Orthopaedic Research, 14 (5): 722–28. (PDF)
  • Badalamente Marie a, Hurst Lawrence C, Benhaim Prosper, Cohen Brian. (2013). “Efficacy and Safety of Collagenase Clostridium Histolyticum in the Treatment of Proximal Interphalangeal Joints in Dupuytren Contracture: Combined Analysis of 4 Phase 3 Clinical Trials.” The Journal of Hand Surgery 38 (10). e54–55. (PDF)
  • Balaguer T, David S, Ihrai T, Cardot N, Daideri G, Lebreton E. (2009). Histological Staging and Dupuytren’s Disease Recurrence or Extension after Surgical Treatment: A Retrospective Study of 124 Patients. J Hand Surg Eur Vol 34 (4): 493–96. (PDF)
  • Ball Catherine, Pratt Anna L, Nanchahal Jagdeep. (2013). “Optimal Functional Outcome Measures for Assessing Treatment for Dupuytren’s Disease: A Systematic Review and Recommendations for Future Practice.” BMC Musculoskeletal Disorders 14 (April): 131. http://www.ncbi.nlm.nih.gov/pubmed/23575442. (PDF)
  • Beasley RW. (2003) Dupuytren’s Disease. In Beasley RW Beasley’s Surgery of the Hand. Thieme: New York 468-487. (PDF)
  • Becker K, Tinschert S, et al. (2015). The Importance of Genetic Susceptibility in Dupuytren’s Disease. Clinical Genetics 87 (5): 483–87. (PDF)
  • Breed CM, Smith PJ. (1996). A Comparison of Methods of Treatment of Pip Joint Contractures in Dupuytren’s Disease. J Hand Surg Br 21 (2): 246–51. (PDF)
  • Brenner P, Krause-Bergmann A, Van VH. [Dupuytren contracture in North Germany. Epidemiological study of 500 cases]. Unfallchirurg. 2001 Apr;104(4):303-11. (PDF)
  • Burge P, Hoy G, Regan P, et al. (1997) Smoking, alcohol and the risk of Dupuytren’s contracture. J Bone Joint Surg Br 79(2): 206–210. (PDF)
  • Coert JH, Nerin JP and Meek MF (2006) Results of partial fasciectomy for Dupuytren disease in 261 consecutive patients . Ann Plast Surg 57(1): 7–13. (PDF)
  • Crowley B, Tonkin MA. (1999). The Proximal Interphalangeal Joint in Dupuytren’s Disease. Hand Clin 15 (1): 137–47 (PDF)
  • Degreef I, De Smet L (2011). Risk Factors in Dupuytren’s Diathesis: Is Recurrence after Surgery Predictable? Acta Orthopaedica Belgica 77 (1): 27–32. (PDF)
  • Degreef I, Steeno P, De Smet L. A survey of clinical manifestations and risk factors in women with Dupuytren’s disease. Acta Orthop Belg 2008 ; 74 : 456-460. (PDF)
  • Descatha A, Carton M, Mediouni Z, Dumontier C, Roquelaure Y, Goldberg M, Zins M, Leclerc A. (2014). Association among Work Exposure, Alcohol Intake, Smoking and Dupuytren’s Disease in a Large Cohort Study (GAZEL). BMJ Open 4 (1): e004214. (PDF)
  • Dias JJ, Braybrooke J. (2006). Dupuytren’s Contracture: An Audit of the Outcomes of Surgery. Journal of Hand Surgery (Edinburgh, Scotland) 31 (5): 514–21. (PDF)
  • Dias JJ, Singh HP, Ullah A, Bhowal B, Thompson JR. (2013). Patterns of Recontracture After Surgical Correction of Dupuytren Disease. J Hand Surg Am 38 (10): 1987–93. (PDF)
  • Diep GK, Agel J, Adams JE. (2015). Prevalence of Palmar Fibromatosis with and without Contracture in Asymptomatic Patients.” Journal of Plastic Surgery and Hand Surgery 49 (4): 247–50. (PDF)
  • Dolmans GH, de Bock GH, Werker PM. (2012). Dupuytren Diathesis and Genetic Risk. J Hand Surg Am 37 (10): 2106–11. (PDF)
  • Dolmans GH, Werker PM, et al. (2011A). Wnt Signaling and Dupuytren’s Disease. The New England Journal of Medicine 365 (4): 307–17. (PDF)
  • Dolmans GH, Werker PM, Hennies HC, et al. (2011B) Supplement to: Wnt signaling and Dupuytren’s disease. N Engl J Med 365:307-17. (PDF)
  • Eaton C. (2015) Recurrent Dupuytren Disease. Orthopaedic Knowledge Online Journal;13(9):3. (PDF)
  • Eckerdal D, Nivestam A, Dahlin LB. (2014). Surgical Treatment of Dupuytren’s Disease – Outcome and Health Economy in Relation to Smoking and Diabetes. BMC Musculoskeletal Disorders 15 (1). BMC Musculoskeletal Disorders: 15:117. (PDF)
  • Foucher G, Cornil C and Lenoble E (1992) Open palm technique for Dupuytren’s disease. A five-year follow-up. Ann Chir Main Memb Super 11(5): 362–366. (PDF)
  • Godtfredsen NS, Lucht H, Prescott E, Sorensen TI, Gronbaek M. (2004). A Prospective Study Linked Both Alcohol and Tobacco to Dupuytren’s Disease. J Clin Epidemiol 57 (8): 63–858. (PDF)
  • Gudmundsson KG, Arngrimsson R, Sigfusson N, Bjornsson A, Jonsson T. (2000) Epidemiology of Dupuytren’s disease: clinical, serological, and social assessment. The Reykjavik Study. J Clin Epidemiol 53: 291–6. (PDF)
  • Hacquebord JH, Chiu VY, Harness NG. (2016). The Risk of Dupuytren Surgery in Obese Individuals. Journal of Hand Surgery 42 (3). 149–55. (PDF)
  • Herweijer H, Dijkstra PU, Nicolai JP, et al. (2007) Postoperative hand therapy in Dupuytren’s disease. Disabil Rehabil 29(22). 2007/09/14.: 1736–1741. (PDF)
  • Hindocha S, John S, Stanley JK, Watson SJ, Bayat A. (2006A). The Heritability of Dupuytren’s Disease: Familial Aggregation and Its Clinical Significance. J Hand Surg Am 31 (2): 204–10. (PDF)
  • Hindocha S, Stanley JK, Watson JS, Bayat A. (2008). Revised Tubiana’s Staging System for Assessment of Disease Severity in Dupuytren’s Disease-Preliminary Clinical Findings. Hand (N Y) 3 (2): 6–80. (PDF)
  • Hindocha S, Stanley JK, Watson S, Bayat A. (2006B). Dupuytren’s Diathesis Revisited: Evaluation of Prognostic Indicators for Risk of Disease Recurrence. Journal of Hand Surgery 31 (10): 1626–34. (PDF)
  • Hueston JT. (1963). The Dupuytren’s Diathesis. In: Hueston JT Dupuytren’s contracture. Edinburgh: E&S Livingstone: 51–63. (PDF)
  • Hueston, J. T. (1990). Dupuytren diathesis. In Dupuytren’s Disease Biology and Treatment (pp. 246–252). (PDF)
  • Jurisic D, Kovic I, Lulic I, et al. (2008) Dupuytren’s disease characteristics in Primorsko-goranska County, Croatia. Collegium antropologicum 32(4). 1209–13. (PDF)
  • Lanting R, Broekstra DC, Werker PMN, van den Heuvel ER. (2014). A Systematic Review and Meta-Analysis on the Prevalence of Dupuytren Disease in the General Population of Western Countries. (PDF)
  • Lanting R, van den Heuvel ER, Werker PMN. (2016). Clusters in Short-Term Disease Course in Participants With Primary Dupuytren Disease. The Journal of Hand Surgery 41 (3). 354–61; quiz 361. (PDF)
  • Legge JW, McFarlane RMM. (1980). Prediction of Results of Treatment of Dupuytren’s Disease. The Journal of Hand Surgery 5 (6): 608–16. (PDF)
  • Logan AJ, Mason G, Dias J, Makwana N. (2005). Can Rock Climbing Lead to Dupuytren’s Disease? Br J Sports Med 39 (9): 44–639. (PDF)
  • Mcfarlane RM (1990) The results of treatment. In: McFarlane R, McGrouther D, and Flint M (eds) Dupuytren’s Disease Biology and Treatment. Edinburg: Churchill Livingstone, pp. 387–412. (PDF)
  • Melamed E, Beutel BG, Goldstein S, Angel D. (2017) Predictors of Outcomes Following Fasciectomy for Dupuytren’s Disease in Diabetic and Non-Diabetic Patients. J Hand Surg Asian Pac 22(3):309-314. (PDF)
  • Mikkelsen OA (1977) Knuckle pads in Dupuytren’s disease. The Hand 9(3). 1977/10/01.: 301–5. (PDF)
  • Moermans J (1991) Segmental aponeurectomy in Dupuytren’s disease. JHS(B) 16(3): 243–254. (PDF)
  • Palmer KT, D’Angelo S, Syddall H, Griffin MJ, Cooper C, Coggon D. (2014). Dupuytren’s Contracture and Occupational Exposure to Hand-Transmitted Vibration. Occupational and Environmental Medicine 71 (4): 241–45. (PDF)
  • Patel M, Freeman NR, Dhaliwal S, Wright N, Daoud Y, Ryan C, Dibella a V, Menter a. (2014). The Prevalence of Dupuytren Contractures in Patients with Psoriasis.” Clinical and Experimental Dermatology 39 (8): 894–99. (PDF)
  • Peimer CA, Blazar P, Coleman S, Kaplan FTD, Smith, Tursi James P, Cohen B, Kaufman G J, Lindau T. (2013). “Dupuytren Contracture Recurrence Following Treatment with Collagenase Clostridium Histolyticum (CORDLESS Study): 3-Year Data.” The Journal of Hand Surgery 38 (1): 12–22. (PDF)
  • Peimer Clayton a, Blazar Philip, Coleman Stephen, Kaplan F Thomas D, Smith Ted, Lindau Tommy. (2015). “Dupuytren Contracture Recurrence Following Treatment With Collagenase Clostridium Histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study]): 5-Year Data.” The Journal of Hand Surgery 40 (8). 1597–1605. (PDF)
  • Rayan GM, Moore J. (2005). Non-Dupuytren’s Disease of the Palmar Fascia. J Hand Surg Br 30 (6): 551–56. (PDF)
  • Reilly, R. M., Stern, P. J., & Goldfarb, C. A. (2005). A retrospective review of the management of Dupuytren’s nodules. The Journal of Hand Surgery, 30(5), 1014–8. http://doi.org/10.1016/j.jhsa.2005.03.005 (PDF)
  • Rombouts JJ, Noel H, Legrain Y, Munting E. (1989). Prediction of Recurrence in the Treatment of Dupuytren’s Disease: Evaluation of a Histologic Classification. J Hand Surg Am 14 (4): 644–52. (PDF)
  • Saboeiro AP, Porkorny JJ, Shehadi SI, Virgo KS, Johnson FE. (2000). Racial Distribution of Dupuytren’s Disease in Department of Veterans Affairs Patients. Plastic and Reconstructive Surgery 106 (1): 71–75. (PDF)
  • Sanderson PL, Morris MA, Stanley JK, Fahmy NR. (1992). Lipids and Dupuytren’s Disease. The Journal of Bone and Joint Surgery. British Volume 74 (6): 923–27. (PDF)
  • Schulze Scott M, Tursi James P. (2014). “Postapproval Clinical Experience in the Treatment of Dupuytren’s Contracture with Collagenase Clostridium Histolyticum (CCH): The First 1,000 Days.” Hand, May. http://link.springer.com/10.1007/s11552-014-9645-7. (PDF)
  • Schurer A, Manley G, Wach W. (2017) International Patient Survey Part 2: Ledderhose Disease. in: Werker PMN, Dias J, Eaton C, Reichert B, Wach (eds) Dupuytren Disease and Related Diseases – The Cutting Edge. Springer, Switzerland, 371-379. (PDF)
  • Smith SP, Devaraj VS, Bunker TD. (2001) The association between frozen shoulder and Dupuytren’s disease. J Shoulder Elbow Surg;10:149 –151. (PDF)
  • Verheyden James R, Freyne Brigid, Frazier Joel L, Kaufman Gregory J, Tursi James P, Smith Ted. (2014). “Effect of Baseline Severity on the Safety and Efficacy of Concurrent Collagenase Clostridium Histolyticum Injections to Treat 2 Dupuytren Contractures.” The Journal of Hand Surgery 39 (9). Elsevier Inc: e30–31. (PDF)
  • Verjee LS, Midwood K, Davidson D, Essex D, Sandison A, Nanchahal J. (2009). Myofibroblast Distribution in Dupuytren’s Cords: Correlation with Digital Contracture. J Hand Surg Am 34 (10): 194–1785. (PDF)
  • Vigroux, J. P., & Valentin, P. (1992). A natural history of Dupuytren’s contracture treated by surgical fasciectomy: the influence of diathesis (76 hands reviewed at more than 10 years). Ann Chir Main Memb Super, 11(5), 367–374. (PDF)
  • Wach W, Manley G. (2017) International Patient Survey Part 1: Dupuytren Disease. in: Werker PMN, Dias J, Eaton C, Reichert B, Wach (eds) Dupuytren Disease and Related Diseases – The Cutting Edge. Springer, Switzerland, 29-40. (PDF)
  • Williams FM, Kalson NS, Fabiane SM, Mann DA, Deehan DJ. (2015). Joint Stiffness Is Heritable and Associated with Fibrotic Conditions and Joint Replacement. PloS One 10 (7): e0133629. (PDF)
  • Witthaut J, Jones G, Skrepnik N, Kushner H, Houston A, Lindau TR. (2013). “Efficacy and Safety of Collagenase Clostridium Histolyticum Injection for Dupuytren Contracture: Short-Term Results from 2 Open-Label Studies.” Journal of Hand Surgery 38 (1): 2–11. (PDF)
  • Zhou C, Hovius SER, Slijper HP, Feitz Rr, Van Nieuwenhoven CA, Pieters HJ, Selles RW. (2015). “Collagenase Clostridium Histolyticum versus Limited Fasciectomy for Dupuytren’s Contracture.” Plastic and Reconstructive Surgery, 136(1) 87-97. (PDF)
Dupuytren Literature
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