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DUPUYTREN LITERATURE: DIATHESIS AND BIOLOGIC SEVERITY

These materials are available for nonprofit educational use. This repository is allowed by copyright disclaimer under title 17, Appendix E, section 107 of the United States Copyright Act. Under this statute, allowance is made for “fair use” for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. As defined, fair use specifically applies to this repository. Also see Notes on Dupuytren Measurement systems (pdf) Clinical Severity Benchmarks:

  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/

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

  • Demographic
    • ↑↑ if Positive family history (Hindocha 2006A, Becker 2014)
    • +FHx ↑ likelihood early onset, ectopic disease, high severity score (Hindocha 2006A severity score based on # DC procedures, # Individual digit recurrences, # Digits affected, # Nodules, Garrod Pads, Ledderhose, Total Tubiana score, # hands affected), although the correlation between family history and age of the first operation is disputed (Coert 2006).
    • ↑ if Caucasian (In US Caucasian > Hispanic > Black > Asian)  (Saboeiro 2000)
    • ↑ if Greater age (Lanting 2014, Descatha 2014)
    • ↑ if Male gender (Lanting 2014)
    • ↑ if high Genetic score (Dolmans 2011, Dolmans 2012) (WNT4 WNT7B WNT2 RSPO2 MAFB DMRT1 DMRT1 EPDR1)
    • 10 X more DD patients without contracture than with (Diep 2015)
    • Less gender difference in asymptomatic disease (Diep 2015)
    • Dupuytren Spectrum diseases effect on risk of developing Dupuytren ↑ if Ledderhose (Schurer 2017) ↑ if Frozen Shoulder (Smith 2001), esp. women (Degreef 2011) ± if Peyronie (Data sampling problem: demographic overlap)
 
 
 

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:

References

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