Report to the Workers' Compensation Board on Dupuytren's Contracture and Hand Injury
September, 1996

Occupational Disease Panel (Industrial Disease Standards Panel)
ODP Report no. 17
Toronto, Ontario


Relevant Link

Dr. Liss Review

Occupational Disease Panel

In 1985, the Ontario legislature established the Industrial Disease Standards Panel to investigate and identify diseases related to work. The Panel is independent of both the Ministry of Labour and the Workers' Compensation Board. At the end of each fiscal year the WCB reimburses the Ministry for the Panel's expenditures. In 1995, the name was changed to the Occupational Disease Panel (ODP).

The Panel's authority flows from section 95 of the Workers' Compensation Act and its functions are set out as follows:

95(8)

(a) to investigate possible industrial diseases;
(b) to make findings as to whether a probable connection exists between a diseas and an industrial process, trade or occupation in Ontario;
(c) to create, develop and revise criteria for the evaluation of claims respecting industrial diseases; and
(d) to advise on eligibility rules regarding compensation for claims.

Decisions of the Panel are made by its members who represent labour, management, scientific, medical and community interests. Once the Panel makes a finding, the WCB is required to publish the Panel's report in the Ontario Gazette and solicit comments from interested parties. After considering the submissions the WCB Board of Directors decide if the Panel's recommendations are to be implemented, amended or rejected.

To assist with its work, the Panel has a small staff of researchers, analysts and support people. In addition to its own staff, the Panel relies heavily on the advice of outside experts in science, medicine and law, as well as input from parties of interest.

Additional copies of this publication are available by writing:

Occupational Disease Panel
69 Yonge Street, Suite 1004
Toronto, Ontario M5E 1K3
(416) 327-4156


Panel Membership

Panel Members Appointment
Ms. Nicolette Carlan (Chair) May 16, 1991 to May 15, 1997
Mr. James Brophy January 23, 1992 to January 22, 1998
Dr. Carol Buck June 1, 1988 to June 16, 1997
Mr. William Elliott November 7, 1991 to November 6, 1997
Mr. John Macnamara November 7, 1991 to November 6, 1997
Mr. Homer Seguin May 28, 1989 to May 27, 1998
Dr. Michael Wills November 7, 1991 to November 6, 1997

Panel Staff

Panel Staff  
Carolyn Archer Senior Research Officer
Robert Chase Medical Consultant
Francis Macri Policy Analyst
Cara Melbye Policy Analyst
Anne Rekenye Data Entry Clerk
Tracy Soyka Administrative Co-Ordinator
Barry Spinner Policy Analyst
Salima Storey Administrative Officer
George Tomlinson Biostatistician
Jason Tung Industrial Hygienist

Tables of Content

Letter of Transmittal
Panel Members
Panel Staff

Chapter 1. The Panel's Investigation
1) The issue and how it arose
2) The Panel's Mandate
3) Investigation of Dupuytren's Contracture

Chapter 2. The Evidence
1) Background information on Dupuytren's Contracture
2) Injury and Dupuytren's Contracture
a) Manual work
b) Vibration exposure
c) Single injury

Chapter 3. Conclusions
1) The Association with Manual Work
2) The Association with Vibration Exposure
3) The Association with Single Injury

Chapter 4. The Panel's Findings and Recommendations

Chapter 5. References

Appendix A.
Occupation and Dupuytren's Contracture by Dr. Gary Liss

Appendix B.
Review of Occupation and Dupuytren's Contracture by Dr. Gary Liss. Review by Dr. Susan Stock

Critical assessment of the review about work- and injury-relatedness of Dupuytren's Contracture. Review by Dr. Andreas Maetzel

Appendix C.
Glossary of some epidemiological terms

Table 1.
Dupuytren's Contracture and Manual Work studies: summary of results

Table 2.
Dupuytren's Contracture and Vibration Exposure studies: summary of results

Table 3.
Dupuytren's Contracture and Hand Injury and Surgery

Figure 1.
Dupuytren's Contracture among Manual Workers

Figure 2.
Dupuytren's Contracture among Vibration Exposed Workers

Figure 3.
Dose/Response.
Cocco - Case control study of Vibration Exposed Workers 14


CHAPTER 1. THE PANEL'S INVESTIGATION

1) The issue and how it arose

In September 1992, the Acting Director of the Office of the Worker Advisor (OWA) requested that the Industrial Disease Standards Panel (IDSP), as it was then called, investigate a possible connection between Dupuytren's Contracture (DC) and work [26]. The OWA was concerned by the fact that Workers' Compensation Board (WCB) policy did not recognize a possible relationship between DC and repetitive strain or other work activity, while the Workers' Compensation Appeals Tribunal (WCAT) had recognized a causal relationship in at least two cases.

2) The Panel's Mandate

The compensation of occupational diseases is enabled by section 1(1) of the Workers' Compensation Act (the Act), which contains the following:

"occupational disease" includes,

(a) a disease resulting from exposure to a substance relating to a particular process, a trade or occupation in an industry,

(b) a disease peculiar to or characteristic of a particular industrial process, trade or occupation,

(c) a medical condition that in the opinion of the Board requires a worker to be removed either temporarily or permanently from exposure to a substance because the condition may be a precursor to an occupational disease, or

(d) any of the diseases mentioned in Schedule 3 or 4; ("maladie professionelle").

In subparagraphs (a) to (c), a disease or medical condition(1) is compensable if it meets the requirements set out in the qualifying language of the whole definition. In (d) scheduled diseases are demonstrably industrial diseases because they meet the definition and therefore are either presumed or deemed to be caused by the employment.

Both law and practice concerning occupational disease compensation are more or less uniform in Canada, despite the fact that some provinces no longer have disease lists or schedules.(2) A compensable disease is therefore any disease that can be shown to be work-related or that is already legally recognized as work-related.

The Occupational Disease Panel (ODP), as it is now called, undertakes the investigation of a possible connection between diseases and work under its mandate in s.95(8) of the Act (Workers' Compensation Act, R.S.O. 1990, c. W. 11, s.95):

95(8) It shall be the function of the Panel,

(a) to investigate possible occupational diseases;

(b) to make findings as to whether probable connections exist between a disease and an occupational process, trade or occupation in Ontario;

(c) to create, develop and revise criteria for the evaluation of claims respecting occupational diseases; and

(d) to advise on eligibility rules regarding compensation for claims respecting occupational diseases.

The ODP examines epidemiological studies, industrial hygiene information on workplace exposures, toxicological evidence on identifiable contaminants and alternative causes of disease. To evaluate this evidence, the Panel uses the concepts of Sir Austin Bradford Hill (1965) [7]. Bradford Hill argued that to determine causality, consideration should be given to the following factors:

1. strength of association 6. biological plausibility
2. consistency 7. coherence
3. specificity 8. experiment
4. temporality 9. analogy
5. biological gradient

After weighing the evidence, the Panel will decide what, if any, probable connection exists between a particular work process and a specific disease. If the results of the investigation do not indicate the existence of a probable connection, the Panel will also report those findings.

When a probable connection is identified, depending on its strength, the Panel may recommend that the WCB take certain steps to ensure compensation for occupational diseases.

3) Investigation of Dupuytren's Contracture

In response to the OWA request, the Chair of the ODP requested a background paper on DC. A literature search was done. Both relevant WCAT decisions and practice in other jurisdictions were examined. In the meantime, more inquiries concerning DC and occupation were received. The background paper, together with a legal memo on ODP 's jurisdiction to investigate DC, was given to the Panel at its meeting in January 1993.

The Panel agreed that it had jurisdiction to investigate the work relationship of DC and the item was placed on the agenda. The Panel requested an expert literature review by a Professor of Dermatology at a major university teaching hospital; however, after a long delay, the one-page document was totally inadequate for further consideration. In September 1993 a second review was requested from Dr. Gary M. Liss of the Ministry of Labour [14].

The literature review was completed in December 1993 and is included in Appendix A. Dr. Andreas Maetzel and Dr. Susan Stock were asked to peer review the document and their comments were received in 1994 [16][25]. The peer reviewers did not make any comments which in the Panel's opinion required a response from Dr. Liss.

Copies of all reviews were next sent for consultation to the following stakeholder groups:

The deadline for stakeholder submissions was set for August 25, 1994. Submissions were received from the OWA and the OFL, both of which supported a possible connection between work and DC [28] [6].

Upon review of the evidence, the Panel requested its staff to re-examine the primary sources. The Panel once again examined the evidence, and the results of that examination form the substance of the Report that follows.


CHAPTER 2. THE EVIDENCE

1) Background information on Dupuytren's Contracture

Dupuytren's Contracture (named after the French surgeon who first lectured on this condition) is a disease of the palmar fascia that causes thickening and contracture of fibrous bands at the palmar surface of the hands and fingers. (The fascia is a sheet of fibrous tissue enclosing muscles and groups of muscles, as well as separating the various layers and groups.) The disease can also affect the feet and shaft of the penis.(3) DC usually occurs bilaterally in hands and feet [14].

DC is more common in men than women (Appendix 1, Tables 2-3); incidence increases with age and is prevalent among 10-20% or more of males by age 60 and 5% or more of females over age 60 [5]. There is an apparent increase of incidence among family members. The disease is also associated with underlying chronic conditions such as diabetes, liver disease (e.g., alcoholism) and epilepsy [14].

Symptoms are slow progressive flexion of the fingers, nodule formation, thickening or retraction of the skin. A classic presentation of the disease (e.g., nodules and visible contracture) poses no diagnostic problems. When visible contracture is absent, the degree of diagnostic accuracy begins to diminish. Symptoms may consist of dull ache, numbness, tenderness and difficulty grasping objects, but some affected patients may have only painless thickening or nodularity beneath the skin of the palm.

Biochemical and histological research have added considerable information on DC although the exact pathogenesis of the disease remains obscure. The nodules and thickened fascia contain an abundance of myofibroblasts, cells that on electron microscopy show contractile elements similar to smooth muscle cells, as well as features similar to fibroblasts that produce collagen thickening. The myofibroblasts found in DC tissue are likely derived from existing populations of fibroblasts and proliferate to a high density producing collagen of an altered composition similar to what occurs during wound healing. Whereas normal palmar fascia contains mainly Type I collagen(4) (composing about 90% of skin, tendon and bone), in DC there is an enormous increase in Type III collagen (10-15% in nodules, 30-40% in fibrous bands, compared to 1-2% found in normal fascia of the palm) [14,22]. Other biochemical changes occurring in DC tissue include a three to four-fold increase in glycosaminoglycan content than in normal skin and a shift towards higher molecular weight proteoglycans in the fascia.

Several of these biochemical changes can be reproduced by culturing fibroblasts at high density; what is still not clear to researchers is what stimulates myofibroblast proliferation, causes tissue contracture and the synthesis of collagen of an altered composition. In wound healing the cells' synthetic functions return to normal, while in DC, increased production of collagen continues.

One plausible hypothesis for the cellular basis of Dupuytren's Contracture is based on the findings of localized microvascular ischemia (deficiency of blood supply) in affected palmar fascia with fibroblasts clustered around narrowed microvessels. Cellular damage from ischemia is known to be mediated in large part by the formation of oxygen free radicals from the stepwise breakdown of adenosine triphosphate (ATP) to hypoxanthine, xanthine and then uric acid; six-fold increases in levels of hypoxanthine in contracture tissue have been found compared with control palmar fascia levels [22]. Oxygen free radicals at the levels similar to those likely to occur in DC, have been shown to have a stimulatory effect on fibroblast proliferation. In this way cellular activity may be triggered by repeated manual trauma or exposure to vibration [3].

2. Injury and Dupuytren's Contracture

Dr. Liss conducted his review of DC to answer the following questions:

1. Is DC associated with manual work involving repetitive injury?

2. Is DC associated with traumatic injury?

Subsequently and independently the Panel and Dr. Liss examined the evidence concerning the association between DC workers exposed to vibratory tools. The results of that work was published by Dr. Liss and Dr. Stock in the American Journal of Industrial Medicine[15].

The literature makes a distinction between heavy (chronic) manual work involving heavy lifting, constant contact with work pieces and tools and vibration exposure from tools or work pieces and machinery. Both manual work and vibration exposure can be described as cumulative injury to the hand or hands. Severe acute or critical injury to the hand or hands can be described as single injury.

a) Manual Work

Manual work includes the chronic use of the hands in lifting, turning, pushing, pulling, banging, hitting, among other things.

Five epidemiologic studies reviewed by Dr. Liss explored whether chronic use of the hands could be related to the development of DC. The quality of the studies was assessed using a modified series of questions developed by Stock in 1991 when she assessed ergonomic factors in musculoskeletal disorders in the upper extremity . The evaluation of studies is described in detail in Dr. Liss' original report in Appendix 1.

Three of the studies found increased prevalence of DC among workers doing manual work, as illustrated in Figure 1. In both the Bennett and Herzog studies the overall odds ratios were elevated but were not statistically significant. In the three subgroups Mikkelsen reported a doubling of elevated rates, all of which were statistically significant. The greatest excess of DC was in the group that Mikkelsen described as engaged in heavy manual labour which included lumberjacks who are also vibration exposed [21]. The five studies are summarized in the following table:

Table 1. Dupuytren's Contracture and Manual Work studies: summary of results

Study Bennett
(1982)
Early
(1962)
Herzog
(1957)
Hueston
(1960)
Mikkelsen
(1990)
Workers Bagging & packing Locomotive Miners & Steel Brewery workers Heavy, med & light work
Comparison/Control Workers- no bag. & pack.. Office workers Clerks > 40 Office workers Workers non-manual
Adjusted Age/sex Age Age Age Gender
Results* OR 5.5
CI 0.8-36.7
OR 0.98
CI 0.6-1.7
OR 1.25
CI 0.6-2.4
OR 0.9
CI 0.6-1.4
OR 3.1 CI 2.2-4.4 heavy
OR 2.7 CI 2.1-3.3 medium
OR 2.0 CI 1.6-2.5 light
Conclusion increased prevalence no difference small increase
not significant
small deficit not
statistically significant
increased prevalence statistically significant

*OR=Odds Ratio
All Confidence Intervals(CI) are 95% unless otherwise stated

In his review for the Panel, Dr. Liss summarized the data in this way:

In summary with respect to the association of DC and manual work, the studies are mostly cross-sectional in design which is inherently limited. The critical appraisal of the available studies indicates that they are poor in quality, without blinding of observers or detailed exposure information. Taken together, they suggest that whether DC is work-related is uncertain. Evidence supporting an association is seen in some studies but not others. The study by Bennett (1982) which appeared to demonstrate the greatest quality showed approximately a doubling of observed DC prevalence compared to that expected. The association cannot yet be considered causal but needs to be confirmed elsewhere [14].

Dr. Andreas Maetzel, one of the peer reviewers, was of the opinion that Dr. Liss had thoroughly reviewed the relevant data and had properly employed scientific methods. In his review of the data Dr. Maetzel wrote:

The author [Dr. Liss] correctly concludes that there is insufficient evidence to definitely say DC is a disease related to manual work. The results, however, strongly suggest a possible association although this remains to be confirmed by future studies [16].

The second peer reviewer, Dr. Stock, found the review to be of good quality and thorough. She offered a slightly different analysis of the data:

My interpretation of the results of the overview of manual work/vibration studies is somewhat different from the author's. Two of the studies rated 14/22, a moderate rating, and met at least the minimum standards for the criteria posing the greatest threat to validity. These studies are of moderately good quality and the only two upon which significant weight can be put. Both demonstrated a significant relationship between manual work or vibration and Dupuytren's contracture. It is only the much poorer studies which had negative conclusions. While these two studies certainly have methodological weaknesses, and therefore their conclusions are not definitive, they do suggest a relationship between this disorder and biomechanical factors at work. The strong dose response relationship noted by Cocco for vibration is also very suggestive that a causal relationship may well exist. Their relationship will need to be confirmed in better designed studies as suggested in Dr. Liss's recommendations [25].

The view of Dr. J.T. Heuston in the Medical Journal of Australia stands in contrast to these opinions which lean towards but do not conclusively support an association between DC and manual work or vibration exposure. Dr. Heuston wrote:

Semantic confusion has always followed the use of the word "trauma" in this discussion. Many regard heavy manual labour either as "trauma" or "micro trauma" to the hand. It is much more likely that the maximum physiological state of the hand is maintained by maximum use [emphasis added]. We have already seen that the opposite condition, disuse, predisposes the hand to the development of Dupuytren's contracture.

If "trauma" is taken literally to mean "a wound" or "a single episode of injury" then a relation can be accepted, but so widespread is the earlier misuse of this term that it better to drop the word "trauma" from the discussion altogether [11].

Heuston goes on to offer an explanation of why people would assume that visible DC is work-related when in fact it is mostly unrelated:

It is human nature to seek an explanation for an unusual occurrence - in this case the painless appearance of a lump in the palm that produces flexion of the finger. Most patients have appeased this natural curiosity by ascribing the nodule to a pressure point on a machine or even their golf grip. The recent misleading English study by McKenney, includes a general practitioner who had driven around his practice for 35 years but had noticed his Dupuytren's nodule only for three months. An aetiological association was claimed between driving and Dupuytren's disease! The same naive report accepts that repetitive grasping of drill-handles damages the palmar aponeurosis by "overstretching" the longitudinal fibres and causing micro ruptures. Such statements then have been quoted in court and it has been necessary to explain that finger flexion in grasping relaxes the longitudinal fibres of the palmar aponeurosis, rather than stretches them. Indeed, powerful flexion does put the fine distal deep transverse fibres of the palmar aponeurosis under strain, but Skoog has found that these fibres are never [added] involved primarily in Dupuytren's contracture [11].

b) Vibration Exposure

The use of hand held, vibration tools leads to cumulative or progressive injury to the hands. Vibrating tools, machinery and work pieces are the usual sources of exposure. Hand-arm vibration syndrome would be a good indicator of chronic exposure.(5)

Five studies reviewed by the Panel examined vibration exposure or manual work with vibration exposure to determine whether chronic

exposure to vibration could be related to the development of DC. Three studies, including the work of Thomas, Cocco and Bovenzi found an approximate two-fold statistically significant increased rate of DC among workers exposed to vibration. In the study conducted by Landrgot there was a slight increase in the rate of DC ( OR 1.2) among maintenance

workers who were compared to clerical workers, but that elevation was not statistically significant. In the study conducted by Patri et al. when lumberjacks were compared to manual workers there was no elevated rate of DC.

The most recent study was a case control study of Italian stone workers conducted by Bovenzi et al. [1]. The authors examined three groups of workers; quarry drillers who used rock breakers and drills, Group A stone carvers who used only rotary tools and Group B stone carvers who used both rotary and percussive tools. These workers were matched with 258 stone workers who did manual labour but used no vibratory tools. In their analysis the authors also controlled for muscular injury, systemic disease, cigarette smoking and alcohol consumption. All three groups of workers experienced elevated rates of DC.

The five vibration studies are more briefly summarized in the following table:

Table 2: Dupuytren's Contracture and Vibration Exposure studies:

summary of results
Study

Thomas&Clarke
(1992)

Cocco
(1987)

Patri
(1982)

Landrgot
(1975)

Bovenzi
(1994)

Cohort Admitted hosp. with VIWFD Vib.. exp & DC Lumberjacks DC vibrations exposed workers Stone cutters/ drillers/carvers
Comparison/ Controls Admitted hosp; no White Finger DC and no vibration exposure Workers no vibration Maint.. & clerical Stone workers no vibration
Adjusted Age Age/sex n/a n/a Age/smoking /alcohol/upper limb injuries etc
Results* OR 2.1
CI 1.1-3.9
OR 2.3
CI 1.5-4.4
OR 0.9
CI 0.5-1.8
OR 1.2
CI 0.8-2.0
OR 2.6 CI 1.1-6.2 Quarry drillers
OR 1.9 CI 0.7-4.6 Stone carvers A
OR 3.2 CI 1.4-7.2 Stone carvers B
Conclusion statistically significant increase statistically significant increase no difference slight elevation statistically significant increased.

* OR=Odds Ratio
All Confidence Intervals(CI) are 95% unless otherwise stated

One of the studies identified was a case control study conducted by Cocco et al [4]. The authors selected 180 cases of workers with DC from the files of the Istituto di Medicina del Lavoro of Cagliara. These worker were matched with other patients who had no visible signs of DC. They were matched for sex, age and date of hospital admission. All workers using any kind of vibratory tools were grouped together according to seniority on their exposed jobs. The results of this study are shown in Figure 3. A dose /response was seen for all workers exposed to vibratory tools. The same findings were confirmed when miners were examined as an individual group.

In his initial review for the Panel, Dr. Liss summed up his evaluation of the data in this way:

With respect to the association of vibration exposure and DC, there is suggestive evidence from studies by Thomas and Clarke (1992) and Cocco et al ( 1987) although not in others. It is possible, however, that the "exposed" workers in the former study (who actually had VWF(6)) may have differed in some way that also predisposed them to develop DC. On the other hand, the inclusion of "manual workers" among the non-exposed group may have diluted or masked the association in some studies. These findings are supported by cases of DC among vibration-exposed workers reported by Roberts (1981),14].

Dr. Liss has modified his first opinion as the result of a review of the work by Bovenzi et al.. Dr. Liss and Dr. Stock now say, in the American Journal of Industrial Medicine:

There is good support for an association between vibration exposure and DC, and the studies we examined met a number of the criteria for causality: there is weaker evidence for such an association with manual work [15].

c) Single Injury

Single Injury refers to an acute injury such as a puncture wound, for example. The nature of injury is therefore specific: a penetrating wound, fracture, burn, laceration, or even a proximal limb dislocation or edema after radical surgery(7). The important facts are swelling and inactivity of the hand for a few days [17].

In his review of the evidence on this point Dr. Liss wrote:

In general authors have been more accepting of this association with DC than with chronic manual work, including Hueston ( 1987) who stated "it is commonplace to see Dupuytren's contracture first appearing in the palm of an elderly woman soon after the removal of a plaster cast for a Colles' fracture."

However, some caution is needed in interpreting this for two reasons: first, among some of the groups affected such as the elderly referred to above, DC is common in general ( prevalence approaching or exceeding 10%); second the impressions are anecdotal. Ideally in order to assess this association epidemiologically, one would compare prospectively the occurrence of DC among a group who had sustained a (single) hand injury with that among a group who had not sustained such an injury. [Alternatively one could compare the prevalence of past hand injury among those with and without DC.] To my knowledge, no such data are available. Despite this, there appears to be more widespread agreement about the relationship with single injury than with manual work [14].

Dr. Heuston opines that there appears to be an association between hand injury and early onset of DC in the absence of other explanations of the disease. Early onset, in this case, refers to the appearance of the disease in a younger age that expected. Other explanations could be manifestations of the disease elsewhere on the body or in an uninjured hand or an underlying condition.

In a study of 309 DC surgical cases, Dr. McFarlane identified 106 patients who had hand injuries prior to the surgery. From this group only 18 cases met three qualifiers to be included in the study; each patient had an injury to his hand, had objective evidence of an injury and had DC in the area of the injury. Finally he excluded those patients who have a related underlying cause or a family history of DC leaving seven patients for his study [17, 18, 19]. The findings can be tabulated as follows:

Table 3: Dupuytren's Contracture and Hand Injury and Surgery
Summary of Results: DC, single hand injury & surgery
DC Age at Injury Age at Disease Age at Operation

Years to Onset

Other Hand?
Right 17 22 -- 5 yrs no DC
Bilat. 29 29 35 <1 yr severe
Bilat. 29 29 35 <1 yr nodule
Bilat. 20 21 40 1 yr progressive
Right 10 ? 39 ? no DC
Right 10 ? 51 ? no DC
Right 24 24 26 <1 yr no DC

Three of the seven cases had bilateral DC, ranging from severe to progressive. In those cases the relatively long time between age of disease onset and age at operation suggests that disease in the uninjured hand developed well after onset in the injured hand. Since the other possible explanations of DC appear to be inapplicable, single hand injury, in this instance seems the best theory for early onset of unilateral DC in the injured hand.(8)

Dr. McFarlane, who has been called to provide expert advice to the WCB and WCAT [20], has posed a set of entitlement criteria for DC claims from an analysis of the surgical record. These criteria, which also reflect findings by Heuston, rest on the presumption that an association between single hand injury and DC is likely in the following circumstances:


CHAPTER 3. CONCLUSIONS

After completing his original literature review Dr. Liss made three recommendations, quoted below:

1. Additional studies of better quality are required to further explore the association of DC with 1) manual work, 2) vibration, and 3) single injury in order to refute or provide further evidence to support these hypotheses. It may be possible to conduct new morbidity studies with improved methodology relatively quickly. This author would be willing to discuss with the Panel how these might be designed.

2. The guidelines for single injury and DC proposed by McFarlane and Shum (1990) might be adapted in the interim.

3. The inconsistency shown in WCAT appeals has been unfair to workers. Workers with "equivalent" past exposures and similar temporal sequences in the development of DC, should be handled by the "system" in a similar manner. The decision to allow appeals in some cases and not others should not depend only on which medical expert happens to be providing evidence.

The Panel gave careful consideration to all of the commentary particularly the recommendation that additional study be undertaken. The Panel declined to undertake additional studies of this issue at this time for two reasons. In the first instance, the Panel does not have the financial resources necessary to conduct the recommended research. Secondly, the Panel is aware of the obligation on it to report in a timely fashion and to await additional research would prevent the Panel from reporting in a reasonable time.

As in all of its work the Panel has attempted to apply the Bradford-Hill criteria to determine the association, if any, between DC and work. In this circumstance the application of these criteria is difficult because diagnosis of DC is made inconsistently and therefore the expected rates of disease are often obscured, the timing of the onset of disease is not precisely documented and the exact type of exposure is unclear. Nonetheless, the Panel has attempted to address the appropriate issues.

The Association with Manual Work

Strength of Association

In three studies (Bennett, Herzog and Mikkelsen) the rates of DC were elevated . Only in the Mikklesen study was the elevation statistically significant for the overall cohort. In Herzog the elevated rate was only 1.25. In the other two studies the rates of DC were close to the expected rates( Early OR 0.98 and Heuston OR 0.9)

On the basis of this evidence the Panel was not persuaded that there was evidence of a strong association.

Consistency

In the Panel's opinion the findings between studies are too varied to be described as consistent.

Dose/response

Mikkelsen showed increased rates of DC with increased intensity of labour. The elevated rates ranged from 2.0 for light manual work to a maximum of 3.1 for heavy manual work. None of the studies attempted to conducted an analysis of the incidence of DC with duration of exposure.

Biological Plausibility

The evidence about the biochemical changes and fibroblast formation after repeated minor traumas offers a biologically plausible explanation for the elevated rates of DC among manual workers.

Coherence

The evidence supported by a dose/response relationship with intensity of exposure and the biologically plausible explanation of biochemical changes suggests that a coherent explanation of the association between manual work and DC is developing. However, the inconsistent evidence of statistically significant elevated rates of DC among manual workers limits the Panel's ability to determine that a coherent theory has been established.

Experimental Evidence

When fibroblasts are grown in culture biochemical changes similar to those in DC patients can be reproduced. This experimental evidence supports the biological explanation of this disease process. There is no evidence that allows the Panel to comment on temporality, specificity or the analogy criteria.

On the basis of this evidence and the advice of the experts retained by the Panel, it concludes that a probable connection between DC and manual work has not yet been established. The connection remains possible, but the Panel does not currently have the resources to undertake further research on this possibility. The necessary research will therefore have to await funding from another source.

Nevertheless, adjudicators in the workers' compensation system will have to make decisions on the basis of individual case evidence. The Panel suggests that when evaluating a claim, and known risk factors (e.g., diabetes, alcoholism, DC at other body sites) have been weighed, the adjudicator give careful consideration to the growing body of evidence which supports an association between DC and manual work.

(By way of comparison, the Quebec IRSST [Institut de recherche en santé et en sécurité du travail] in a study of musculoskeletal injuries and work finds that, in the research that meets its criteria, the evidence is inconclusive for work-related DC.)

The Association with Vibration Exposure

Strength of Association

Thomas and Clarke found an almost three -fold statistically significant increase of DC among vibration exposed subjects. Cocco found a two-fold prevalence of DC among workers exposed to vibration compared to the occurrence of DC among non-vibration exposed workers. The strongest evidence of association is found in a study of HAVS in stone cutters and stone carvers in Italy. In that study conducted by Bovenzi et al. the statistically elevated rates ranged from 1.9 to 3.2.

Consistency

In four of the five studies that examined vibration exposure and DC there were elevated rates of the disease. The exception was the work by Patri which compared vibration exposed workers to manual labourers and that study showed a incidence rate 0.9. The reliability of the comparison made by Patri in 1982 may now be deemed questionable given the growing body of evidence which suggests that manual work may affect the incidence of DC.

In the opinion of the Panel the repeated finding of elevated rates of DC in different studies satisfies the consistency criteria.

Dose/ Response

In the only study to conduct a dose/ response analysis, that of Cocco, 1987, the findings supported a statistically increasing risk of disease with duration of exposure.

In the opinion of the Panel this supports the dose/response criteria.

Biological Plausibility

The evidence about the biochemical changes and fibroblast formation after repeated minor traumas offers a biologically plausible explanation for the elevated rates of DC among vibration exposed workers.

Coherence

The evidence which provides for a biological explanation, consistently elevated rates of DC among vibration exposed workers established to the Panel's's satisfaction a coherent picture of the association between DC and vibration exposure.

Experimental Evidence

When fibroblasts are grown in culture, biochemical changes similar to those in DC patients can be reproduced. This experimental evidence supports the biological explanation of this disease process.

There is no evidence that allows the Panel to comment on temporality, specificity or the analogy criteria.

The Panel finds that there is sufficient evidence to confirm a probable relationship between DC and vibration exposure. The association is even stronger in the presence of HAVS. The Panel is also of the opinion that the evidence is sufficiently strong to warrant the development of guidelines which support payment of claims for workers with DC exposed to vibration.

The Association with Single Injury

Concerning single hand injury, Dr. Liss wrote in his review for the Panel:

In general there has been more acceptance by clinicians and compensation boards of the association of DC with single injury than with chronic manual work. However, the impressions are anecdotal. To our knowledge, no epidemiological investigations have been conducted to study this association. The microscopic similarities between DC and wound healing, and the obvious stimulus to the fibroblasts after trauma do however, support the case for biological plausibility [14] .

This anecdotal evidence can be distinguished from the carefully designed epidemiological studies that are usually available to the Panel when it reaches its conclusions. Whenever possible the Panel likes to base its conclusions on well designed studies which allow for statistical analysis and control for all the variables. However, at times decisions must be made on the basis of the best available evidence and in this case that is the anecdotal evidence of surgeons. While it would be possible to await more evidence on this issue, the Panel is of the opinion that it is necessary to make a comment on the association between single injury and DC. While scientists are designing better studies and gathering more information; adjudicators are finding it difficult to evaluate the evidence before them, as Dr. Liss has pointed out.

The evidence from case reports and the record of DC surgical cases indicates a relation between hand injury and early onset of DC in the injured hand. The hand injury must be critical and referable to a singular event; thus, a penetrating wound, a crush injury, fracture or laceration, among others, should be considered as single injury. The nature and extent of injury, the age at onset, the latency period after injury, family history and underlying conditions would have to be clarified to decide compensability.

Current research indicates that DC develops bilaterally and is age and family related. Early onset of unilateral disease therefore results from either an aggressive course of disease or from some other mechanism of acceleration in susceptible individuals, such as hand injury.

For example, Table 3 shows two cases where injury occurs at a very young age; regardless of missing data, there is still onset at a much younger age than expected and without bilateral disease. Excepting injury to both hands, the only medical explanation for bilateral DC appears to be genetic predisposition or underlying condition. In the case of single hand injury, if bilateral disease manifests well after injury (e.g., five years), then early onset in the injured hand can be related to the injury.

All of this evidence leads the Panel to conclude that a probable connection exists between the onset of DC in a hand following an injury. The type of evidence necessary to substantiate the occurrence of an injury and the onset of DC makes it most appropriate for the Board to develop guidelines for the use of adjudicators.


CHAPTER 4. THE PANEL'S FINDINGS AND RECOMMENDATIONS

The incidence and prevalence of Dupuytren's Contracture are related to age, family history, and to certain underlying conditions.

Dupuytren's Contracture and Manual Work

The Panel finds the evidence of an association between manual work and Dupuytren's Contracture inconclusive and a probable connection has not yet been established. A possible connection, however, should be examined case-by-case on the evidence.

The Panel recommends that claims for Dupuytren's Contracture and manual work should be adjudicated on their own merits on a case-by-case basis, having regard to all the factors identified in this Report that relate to the relationship between Dupuytren's Contracture and manual work.

Dupuytren's Contracture and Vibration Exposed Workers

The Panel finds a probable connection between Dupuytren's Contracture and vibration exposure. The evidence is of sufficient strength to substantiate workers' compensation benefits for workers who experience Dupuytren's Contracture following exposure to vibratory tools in the workplace.

The Panel recommends that the WCB develop guidelines which would entitle workers who are suffering from Dupuytren's Contracture and have been exposed to vibratory tools at work to compensation benefits.

Dupuytren's Contracture and Single Injury

The Panel finds a probable connection exists between single injury and early onset of Dupuytren's Contracture in the injured hand or hands. Because of the nature of the association, payment of compensation should be regulated by guidelines.

The Panel recommends that claims for Dupuytren's Contracture and single injury should be adjudicated on their own merits by applying the following criteria as guidelines:

a) there is evidence of work-related hand injury;

b) the injury is acute, the result of a singular event;

c) the disease appears in the injured hand or hands and is not present at other body sites;

d) the temporal relationship between injury and onset is reasonably short.


CHAPTER 5. REFERENCES

1. Bovenzi, M.; et al. Hand-arm vibration syndrome and dose- response relation for vibration induced white finger among quarry drillers and stonecarvers. Occupational and Environmental Medicine. 51 (1994). p.603-611.

2. Bennett, B.; Dupuytren's contracture in manual workers. British Journal of Industrial Medicine. Vol.39(1982). p.98-100.

3. Chase, R .; Biochemical changes related to Dupuytren's Contracture. Internal correspondence. July, 1996.

4. Cocco, P.L.; et al.; Occupational exposure to vibrations and Dupuytren's disease: a case control-study. Med Lav. Vol.78(1987). p.386-392.

5. Early, P.F.; Population studies in Dupuytren's contracture. Journal of Bone and Joint Surgery. Vol.44B(1962). p.602-613.

6. Edwards, V.; Occupational Health and Safety Director, Ontario Federation of Labour. [Comments on "Occupation and Dupuytren's contracture" by Dr. Gary Liss.] Aug,26, 1994.

7. Egawa, T.; Senrui, H.; Horiki, A.; Egawa, M. Epidemiology of the oriental patient. In: McFarlane, R. M.; McGrouther, D. A.; Flint, M.H.; eds. Dupuytren's Disease: Biology and Treatment. New York: Churchill Livingstone, 1990. p.239-245.

8. Herzog, E.G.; The aetiology of Dupuytren's contracture. The Lancet. Vol.1(1951). p.1305-1306.

9. Hill, A.B.; The environment and disease: Association or causation? Proceedings of the Royal Society, Section of Occupational Medicine. Vol.58(1965). p.295-300.

10. Hueston, J.T.; The incidence of Dupuytren's contracture. Medical Journal of Australia. (1960). p.999-1002.

11. Hueston, J.T.; Dupuytren's Contracture: medicolegal aspects. The Medical Journal of Australia. Vol.47, Special Suppl(1987). p.S2- S10.

12. Institut de recherche en santé et en sécurité du travail du Québec. Evidence of work-relatedness for selected musculoskeletal disorders of the neck and limbs. In: Work-related musculoskeletal disorders, Chapter 3:19, IRSST, November 16,1993.

13. Landrgot, B.; Huzi, F.; et al. The incidence of Dupuytren's contracture in workers in hazards of vibration. Pracov Lek Vol.27(9)(1975). p.331-333.

14. Liss, G.M.; Occupation and Dupuytren's Contracture. Ontario Ministry of Labour, 1993.

15. Liss, G.M.; Stock, S.; Can Dupuytren's Contracture be work-related? Review of the evidence. American Journal of Industrial Medicine. Vol.29,no.5(1996). p.521-532.

16. Maetzel, A.; Ontario Workers' Compensation Institute. "Critical assessment of the review about work- and injury-relatedness of Dupuytren's contracture" [Comments on "Occupation and Dupuytren's contracture" by Dr. Gary Liss.] June 4, 1994.

17. McFarlane, R.M.; Dupuytren's disease: relation to work and injury. Journal of Hand Surgery. Vol.16A, no.5(1991). p.775-779.

18. McFarlane, R.M.; McGrouther, D.A.; Flint, M.H.; eds. Dupuytren's Disease: Biology and Treatment. 'The Hand and Upper Limb', Vol.5. New York: Churchill Livingstone, 1990.

19. McFarlane, R.M.; Botz, J.S.; et al. Epidemiology of surgical patients. In: McFarlane, R.M.; McGrouther, D.A.; Flint, M.H.; eds. Dupuytren's Disease: Biology and Treatment. New York: Churchill Livingstone, 1990. p.201-238.

20. McFarlane, R.M.; Dupuytren's Disease: Relation to work and injury. Prepared for the Ontario Workers' Compensation Board, July 1989.

21. Mikkelsen, O.A.; Epidemiology of a Norwegian population. In: McFarlane, R.M.; McGrouther, D.A.; Flint, M.H.; eds. Dupuytren's Disease: Biology and Treatment. New York: Churchill Livingstone, 1990. p.191-200.

22. Murrell, A.C.; The role of the fibroblast in Dupuytren's contracture. Hand Clinics. Vol.7,no.4(1991). p.669-680.

23. Patri, B.; Vayssairat, M.; et al. Epidemiology and clinical studies of the lumberjack's white finger syndrome. Arch Mal Prof. Vol.43(1982). p.253-259.

24. Seyfer, A.E.; Hueston, J.T.; eds. Hand Clinics: Dupuytren's Contracture, Vol.7, no.4. Philadelphia: W.B. Saunders Company 1991.

25. Stock S.; [Review of "Occupation and Dupuytren's contracture" by Dr. Gary Liss.] April, 1994

26. Tait, R.; Acting Director, Office of the Worker Adviser. [letter to N. Carlan, Chair IDSP, requesting a review of Dupuytren's contracture and its causal relationship with repetitive strain or other employment activity]. Sept, 28, 1992.

27. Thomas, P.R.; Clarke, D.; Vibration white finger and Dupuytren's contracture. Journal of Society of Occupational Medicine. 1992. Vol.42(3) p.155-158.

28. Wilken, D.; Legislation Interpretation Office, Office of the Worker Adviser. [Comments on "Occupation and Dupuytren's contracture" by Dr. Gary Liss.] Aug. 25, 1994.


APPENDIX A.
OCCUPATION AND DUPUYTREN'S CONTRACTURE


Gary M. Liss, MD, MS, FRCPC
Health and Safety Studies Unit
Ontario Ministry of Labour
December 1993

TABLE OF CONTENTS

Table of Contents

Summary

Definitions of Some Terms Used in the Report

Some Abbreviations in the Report

Background

1.0 Introduction

2.0 Historical Vignette

3.0 Clinical Diagnosis (Symptoms and Signs)

4.0 Some Epidemiological Characteristics of this Condition

5.0 Pathogenesis

6.0 Associations with Occupation (Manual Work/ Vibration)
   6.1 The scene
    6.1.1 Occupational Associations: Historical Perspective
   6.2 Search Methods
   6.3 Limitations of Existing Investigations of this Problem
   6.4 What about the WCAT Decisions to date?
   6.5 Summary of Previous Articles and Reviews
        6.5.1 What do occupational medicine texts say?
        6.5.2 Articles focussing on Dupuytren's Disease
        6.5.3 Summary
   6.6 Methods for Consideration of Original Articles
   6.7 Results of Evaluation of Original Investigations
        6.7.1 Selection of Studies
        6.7.2 Validity Assessment of Studies
        6.7.3 Study Findings

7.0 Single Injury and Dupuytren's Contracture

8.0 Discussion and Conclusions

9.0 Recommendations

Acknowledgements

References

Tables

Appendices

SUMMARY

In September 1993, this author was asked by the Industrial Disease Standards Panel to conduct a literature review on Dupuytren's Contracture, and its relationship with work. This review began in November 1993.

Dupuytren's Contracture (DC) is a disease of the palmar fascia (aponeurosis) resulting in thickening and contracture of fibrous bands on the palmar surface of the hands and fingers; the principal clinical deformity is a slowly progressive flexion of the fingers. The clinical picture includes nodules (which are usually central to the diagnosis), thickening or retraction of the skin, cords and bands, and finally, joint contracture. The ring finger has been most frequently affected in many series, followed by the little finger. The condition may be asymptomatic, even after contracture has developed, while others may complain of aching, tinging or difficulty grasping objects; some eventually require surgery.

Although the pathogenesis of DC remains obscure, cellular and biochemical changes have been identified. Microruptures and microhemorrhages within the aponeurosis have been hypothesized by some writers as an important factor in the pathogenesis, although this has been by no means universally accepted.

The condition is more frequent in males than females, and increases with age reaching 10-20% or higher among males, and 5% or higher among females by the 60s. There appears to be an increased incidence of DC among family members. It is frequently bilateral, but when unilateral, it has been somewhat more frequent in the right than left hand in some series. Some have considered there to be a "Dupuytren diathesis"; in its extreme interpretation, the inherited predisposition is essentially the only way one can develop DC. For example, Hueston (1987) wrote "Thus, when a patient asks now 'Why have I got it?', we should simply tell the patients that he or she was 'born to get it'!". The condition is also associated with diabetes mellitus, liver disease and epilepsy.

When examining associations with occupation, two different aspects can be considered: (1) whether DC is associated with chronic manual or repetitive work (including vibration); and (2) whether the condition is associated with a single injury.

On reviewing the literature, a number of serious problems and limitations became apparent, which should be borne in mind. These include that there may be difficulty in diagnosing the condition, and the observed prevalence may vary with what criteria are used; cases going to surgery may not be representative of all cases; studies did not always stratify by or separate genders or age groups; there was no blinding of examiners to exposure in the original studies; and there have been problems with terminology, for example, inconsistent use of the term "injury" with failure to distinguish between "injury" and "trauma', the latter used interchangeably with "manual labour" and "repetitive trauma".

Summaries of some recent WCAT decisions were forwarded to this writer. The phrases used to describe whether an association with "heavy work or manual work" has been shown in the "medical literature", varied dramatically from decision to decision, no doubt causing a real inconsistency in the decisions made, which may occur even among individual workers with similar circumstances/ exposures. The workers who appealed their cases to WCAT were employed in a variety of industries/ occupations, including a number from the automotive industry.

Manual work/ vibration and Dupuytren's Contracture: Occupational medicine texts have largely ignored this subject, while much of the writing has come at this subject from a "surgical" perspective, which perhaps is not unreasonable, given that most of the patients are seen by surgeons. There is some support in past reviews for the possibility that manual work might aggravate rather than cause the condition, but in general largely reflects what was noted above: acceptance of a "genetic predisposition".

Methods for consideration of original articles: To examine what has been reported in original articles regarding this association, the published literature was searched for studies meeting the following criteria: 1) in English (if English summary of non-English summary was obtained and was suggestive, a translation was obtained); 2) controlled studies (that is cohort, case-control or cross-sectional studies, with comparison groups) (case reports and case series of DC or of DC coming to operation were excluded); 3) where DC was an outcome identified; and 4) the group of interest had exposure to manual or repetitive work, or vibration. The validity of the studies was assessed using a series of questions adapted from that of Stock (1991) in her review of ergonomic factors in musculoskeletal disorders of the neck and upper limb (see Appendix 2).

Study findings: The six English studies that met these criteria are summarized in Table 5, and for these, odds ratios (ORs) and 95% confidence intervals have been calculated (Table 6). Translated articles are summarized in Table 8. For manual work, two studies found no association with DC, one found a weak, non-significant association, while two found significant "positive" associations: Bennett (1982) found the prevalence at a U.K. PVC bagging and packing plant to be 5.5 times that at a local plant without bagging, while compared to the expected age-specific prevalence from a previously studied U.K. population reported by Early (1962), there were 16 observed cases versus about 8 expected. In a population-based survey of a Norwegian town by Mikkelsen (1978, 1990), the gender-adjusted ORs for the presence of DC compared to non-manual work, were 3.1, 2.7, and 2.0, respectively, for heavy, medium and light type of work. For vibration, Thomas and Clarke (1992) found that the prevalence of DC among a series of claimants in the U.K. considered to have vibration white finger (VWF) was about twice that among a consecutive series of subjects admitted to a general hospital for surgery. Cocco et al (1987) conducted a case-control study in which a history of vibration exposure was significantly higher among cases of DC compared to controls without DC (odds ratio 2.3, 95% confidence interval 1.5-4.4), while two studies found no association of DC with vibration-exposed workers compared to control "manual" workers.

The validity assessment of these studies (Table 7), revealed that their quality was rather poor. In none, were examiners of hands for DC blinded to the exposure status of participants; "exposure" was little more than job title. The quality rating was highest for the study by Bennett (1982).

Single injury and Dupuytren's: Some have written that it is natural for those who suffer from DC to blame a single accident; indeed a number of case reports have been published, which are anecdotal and cannot be used to demonstrate an association. There is more widespread agreement in past writing that DC might arise following a single injury than due to manual work. However, this reviewer was not able to find original studies comparing the occurrence of DC among those who had and had not sustained a hand injury. McFarlane et al (1990a) did analyze a large series of surgical cases of DC, but this does not reflect all DC cases. Within this surgical series involving over 1000 cases, variables that were significantly associated with patients who related a single injury to the onset of disease, included being male, age at onset if male less than 45 years, manual labour, and unilateral disease.

After further review of their surgical cases, based on a history of single injury to the hand, objective evidence of tissue damage such as scarring or healed fracture, and DC in the area of injury, McFarlane and Shum (1990) identified 7 patients considered to have "DC related to work", each of whom was injured before age 30 (crush injury in 2, laceration in 4, fracture in 1). The reason given for this categorization was "early onset". No indication was given regarding the reproducibility of their classification. They concluded that "occasionally a single injury can precipitate the onset of DC". They suggested a list of what they felt could serve as guidelines when establishing a relationship between a single injury and the onset of this condition including DC in the area of the injury of the hand, the appearance of DC within 2 years of injury, and the appearance of DC before age 40 in men and 50 in women unless the individual expresses a "strong diathesis".

These guidelines should be welcomed as a first attempt. However, this writer has some difficulty with the 2 year rule and the 40 year age rule, as is explained in the text. In fact, the 2 year rule is not consistent with one of the authors' 7 so called cases of "DC related to injury" in which the interval between injury and disease was 5 years.

In summary, with respect to the association of DC and manual work, the studies are mostly cross-sectional in design which is inherently limited. The critical appraisal of the available studies indicates that they are poor in quality, without blinding of observers or detailed exposure information. Taken together, they suggest that whether DC is work-related is uncertain. Evidence supporting an association is seen in some studies but not others. The study by Bennett (1982), which appeared to demonstrate the greatest quality showed approximately a doubling of observed DC prevalence compared to that expected. The association cannot yet be considered causal but needs to be confirmed elsewhere. With respect to the association of vibration exposure and DC, there is suggestive evidence from studies by Thomas and Clarke (1992) and Cocco et al (1987) although not in others. It is possible, however, that the "exposed" workers in the former study (who actually had VWF) may have differed in some way that also predisposed them to develop DC. On the other hand, the inclusion of "manual workers" among the "non-exposed" group may have diluted or masked the association in some studies. These findings are supported by cases of DC among vibration-exposed workers reported by Roberts (1981).

With respect to the association of single injury and DC, there do not appear to be data to allow one to compare directly the development of DC among those who have and have not sustained a hand injury. Thus, additional study is necessary before one can comment properly on the association. However, the microscopic similarities between DC and wound healing, and the stimulus after injury to the (myo)fibroblasts suggest biologic plausibility. The analysis of the surgical series by McFarlane et al (1990a), and the guidelines proposed by McFarlane and Shum (1990) may be a reasonable starting point, although there is disagreement with certain components.

Recommendations made include that (1) additional studies of better quality be undertaken to explore these associations further; (2) in the interim, the guidelines proposed by McFarlane and Shum for DC and single injury could be applied; and (3) the inconsistency in WCAT proceedings should be altered so that the commentary on the association itself should not change from case to case, a practice which seems unfair.

DEFINITIONS OF SOME TERMS IN THE REPORT

aponeurosis
a fibrous sheet or expanded tendon, giving attachment to muscular fibres and serving as the means of origin or insertion of a flat muscle; it sometimes also performs the office of a fascia for other muscles

campodactyly
permanent flexion of one or more interphalangeal joints of one or more fingers, usually the little finger

Dupuytren's Contracture
some writers also use the term "Dupuytren's Disease"; a disease of the palmar fascia resulting in thickening and contracture of fibrous bands on the palmar surface of the hands and fingers

Dupuytren's Disease
Dupuytren's Contracture

diathesis
the constitutional or inborn state disposing to a disease, group of diseases, or metabolic or structural anomaly

fascia
a sheet of fibrous tissue that envelopes the body beneath the skin; it also encloses muscles and groups of muscles, and separates their several layers or groups

palmar aponeurosis
the thickened, central portion of the fascia ensheathing the hand; it radiates toward the bases of the fingers from the tendon of the palmaris longus muscle

Source: Stedman's Medical Dictionary (1982)


SOME ABBREVIATIONS IN THE REPORT

DC
Dupuytren's Contracture

DD
Dupuytren's Disease; some writers use this term instead of Dupuytren's Contracture

HAV
Hand-arm vibration

RCT
Randomized controlled trial

VWF
Vibration white finger

WCAT
Workers' Compensation Appeals Tribunal

BACKGROUND

In September 1992, the Chair of the Industrial Disease Standards Panel (IDSP) received a letter from Ms. Rosemary Tait, Acting Director of the Office of the Worker Adviser, asking the IDSP to consider undertaking a review of Dupuytren's Contracture and its causal relationship with repetitive strain or other employment activity.

In September 1993, this author was asked by the IDSP to review the literature on the subject. Work on this review began in November 1993; the last translated article was forwarded from the IDSP on December 15, 1993. In this report, the clinical picture of Dupuytren's Contracture and conditions associated with it are summarized. Then, existing articles and reports are reviewed to address the questions: (1) Is Dupuytren's Contracture associated with manual work (possibly involving repetitive tasks and/ or vibration; not involving a single injury)?; and (2) Is Dupuytren's Contracture associated with a history of having had a single (hand) injury? Finally, the evidence from original epidemiologic studies of adequate quality addressing Question (1) are considered.

1.0 INTRODUCTION

Dupuytren's Contracture (DC) is a thickening of the tissue pad under the palm of the hand; the principal clinical deformity is a slowly progressive and irreversible flexion of the fingers (Glimcher and Peabody, 1990). At its end stage, this shortening is termed a contracture.

Other names for the condition include Dupuytren's disease; maladie de Dupuytren; palmar fibromatosis.

2.0 HISTORICAL VIGNETTE

In 1831, Guillaume Dupuytren, a French surgeon, described permanent retraction of the fingers in Paris. This was published in a French journal the next year and in the Lancet in 1834 (Dupuytren, 1834). The possible role of occupation or manual work has been a matter of discussion, controversy and disagreement since at least that time since Dupuytren's original patients included a wine merchant who gave a history of lifting a cask and noted a cracking sensation in the palm of the hand, a 40-year old coachman with bilateral contractures, and one who had had a previous penetrating wound with a piece of wood. However, the role of occupation has been questioned in these original patients (Hueston, 1987; Hueston and Seyfer, 1991; Moorhead, 1953).

Descriptions of this condition can be found much earlier; for example, in 1614, Felix Plater of Basel described DC as reported by Elliot (1990):

"Contracture of the fingers of the left hand into the palm. A certain well-known master mason, on rolling a large stone, caused the tendons to the ring and little fingers in the palm of the left hand to cease to function. They contracted and in so doing were loosed from the bonds by which they are held and became raised up, as two cords forming a ridge under the skin. These two fingers will remain contracted and drawn in forever." 'Translated by J. B. St. Clair, 1987'

3.0 CLINICAL DIAGNOSIS (SYMPTOMS AND SIGNS)

The clinical features and associated conditions have been reviewed in a number of sources (e.g. McGrouther, 1990; Viljanto, 1973; Anonymous, 1972; Anonymous, 1976). There is little confusion in recognizing advanced cases of DC but "by contrast, in epidemiological surveys the minor signs challenge even the most experienced observer to distinguish between DD and the normal hand in which there is just thick skin or prominent fascia". This feature is particularly important to bear in mind when interpreting the results of previous epidemiologic investigations or surgical series. Moreover, there are "no helpful ancillary diagnostic tests" (McGrouther, 1990) or "no confirmatory tests" (Simmons and Koris, 1992).

Symptoms: There may be no symptoms whatsoever with painless thickening or nodularity in or beneath the skin of the palm. Sometimes, even the contracture "may be well established without producing any pain or discomfort" (Viljanto, 1973). Alternatively, an affected patient may complain of dull ache, numbness or tingling in the palm. The nodule(s) may be tender, and patients may complain of difficulty grasping objects. Other than painful nodules, Dupuytren's disease is usually painless (Simmons and Koris, 1992). In a population-based study by Mikkelsen (1972, 1978, 1990), nodules were the first aspect recognized in 90%, local tenderness was the first symptom in 5%, and finger contracture in 5%.

Signs: The findings on physical examination may vary with the stage of the disease. Skoog (1963) described the clinical facts as: the earliest sign of DC is a nodular thickening of the palmar aponeurosis, the longitudinal fasciculi of the aponeurosis, where the nodules appear, change into tendon-like cords, which retract and cause permanent flexion of the corresponding fingers. The main components (McGrouther, 1990) include nodule; skin changes; changes in the fascia; and joint contracture:

1) nodule: this has been central to most definitions of DC, variously described as "a simple nodular or banded thickening of fascia", "a pathognomonic nodular thickening and retraction of the palmar aponeurosis" (Skoog, 1948); the earliest stage being a nodule without finger contracture (Early, 1962). Dupuytren's nodules usually are observed just proximal or distal to the distal crease of the palm, in the proximal segment of the finger, or at the base of the thumb. The nodule "that appears in an unusual location, such as the base of the hypothenar eminence or at the distal crease of a finger" "poses a diagnostic problem" (McGrouther, 1990). Palpable nodules are considered by many to be diagnostic of DC, but they are not invariably present as they may disappear in the later stages of the disease. However, experts may disagree with this; McFarlane and Shum (1990) in classifying a surgical series of DC cases, considered cases where the nodules disappeared as "not Dupuytren's disease".

2) Skin changes: Involvement of the skin may consist of retraction, thickened tissue, tethering, loss of normal mobility of pretendinous bands, and "pits or dimples" (a form of tethering where the contracting fascia inserts into the dermis (McGrouther, 1990).

3) Cords and bands (changes in the fascia): Cords are contracted bands (McGrouther, 1990) that may be palpable within the palm or digits or may be deeper within the tissues and are found at operation. A clear distinction between a cord and a nodule is "often not possible" (McGrouther, 1990).

4) Joint contracture: Contracture of a joint may be defined as a loss of part of its range of motion. Severe flexion contractures of one or more fingers interfere with the patient's ability to work (e.g. to grasp objects). Usually, flexion appears first in the metacarpophalangeal joints of the ring finger, and later in one or both of the adjoining fingers (Viljanto, 1973). The proximal interphalangeal joint (PIP) will become contracted after this, while the distal interphalangeal joint may be hyperextended. In one large series, the ring finger was affected most frequently, followed by the little finger, with the thumb and index finger rarely involved (Mikkelsen, 1990); this pattern has been observed elsewhere. The contracture can progress at variable rates. These (permanent) contractures may require surgery, and may recur.

In some cases, changes similar to DC may be found in other parts of the body, including the feet (contracture plantar aponeurosis), the penis (Peyronie's disease), and knuckle changes on the extensor side of the hand (knuckle pads).

Reproducibility of diagnosis: Lennox et al (1993) reported on the degree of clinical agreement between two orthopedic surgeons who independently examined 200 consecutive patients on geriatric wards in Aberdeen, Scotland. There was perfect agreement for observing flexion contractures (kappa 1.0), while for skin tethering, palmar nodules and knuckle pads, there was moderate to good agreement (kappas of 0.8, 0.7, and 0.7, respectively).

Differential diagnosis: In its typical form, DC is easy to diagnose, as nodular thickening and retraction of the palmar aponeurosis are lacking in conditions that might cause confusion. However, McFarlane (1991) and McFarlane and Shum (1990) emphasized the need for a histologic diagnosis. Conditions in the differential diagnosis (Viljanto, 1973; McGrouther, 1990) include congenital flexion deformity of fingers, flexion contractures in patients secondary to the hand being kept habitually closed (e.g. after organic disease of the central nervous system, strokes), scleroderma, joint afflictions like rheumatoid arthritis, tumours in the palm of the hand or campdodactyly (permanent flexion of one or more fingers, usually little finger, present from childhood or adolescence). Some authors include posttraumatic contractures among the conditions to be differentiated but this leads to confusion, given that some feel that DC may, in certain circumstances, arise after a single injury.

4.0 SOME EPIDEMIOLOGICAL CHARACTERISTICS OF THE CONDITION

A number of characteristics associated with DC are well-recognized (Mikkelsen, 1990; Simmons and Koris, 1992; Anonymous, 1972; Anonymous, 1976). The condition is seen much more frequently in males than females (a ratio of six to 10 times is frequently quoted but the male:female ratio varies according to age [Table 1]). The prevalence increases dramatically with age (Table 1). Consequently, any estimates will depend on the age distribution of the population studied, and is an important confounder to include in epidemiological studies of other characteristics. In the Norwegian investigation by Mikkelsen (1990), the prevalence was 10.5% in males, and 3.1% in females but reached 20-25% among those 65 years and older (Anonymous, 1972; Anonymous, 1976). DC tends to start earlier in males than females (but again recognition of time of onset may not be accurate). The age of onset (again subject to recognition problems) for one-half of those affected was between 40-59 in males and 40-69 in females (Mikkelsen, 1990).

The condition is commonly bilateral, but when unilateral, more frequently affects the right side (Tables 2 and 3), although in one series similar proportions with the left and right affected were reported (Yost et al, 1955). Mikkelsen (1990) observed that there was usually a greater degree of contracture in the right than left hand. Some conditions which have been mentioned most frequently to be associated with DC include diabetes mellitus, cirrhosis and/ or alcoholism, and epilepsy (Hurst and Badalamente, 1990). Rheumatoid arthritis may be found less frequently among those with DC than among those without (Arafa et al, 1984).

"Dupuytren diathesis": Many writers have emphasized that DC is an inherited disorder or that some have a diathesis to develop DC (Hueston, 1990; Hueston, 1987; Hueston and Seyfer, 1991; McGrouther, 1990a; Hueston, 1985); as might be expected, these writers tend to be those who discount the possibility that the condition is work-related. Diathesis has been defined as "a permanent condition of the body which renders it liable to a special disease". Hueston (1990) commented further that "this permanence has been demonstrated to depend on an inherited genetic pattern or 'dispostion' of the chromosomal material responsible for the development of DD. Therefore it should be clear that it is impossible for a patient with DD to have no diathesis." Supporters of this approach, it appears, consider that the genetic or inherited factors dominate in the "causation" discussions; they maintain that such conditions are "aggravating factors" increasing the strength of the Dupuytren's predisposition or "diathesis" (Hueston, 1990). That DC occurs bilaterally in many cases has been considered by some to reflect a predisposition or genetic factors.

In fact, there is an increased incidence of the condition among family members of affected subjects; it has been suggested that there may be evidence for autosomal dominant inheritance. In one analysis, the number of affected relatives rose from 16% on history taking to 68% after examination of relatives (Ling, 1963). Ling also pointed out the difficulties of establishing the prevalence (and family pattern) of a condition with an onset in middle age at which time older relatives may have died without diagnosis.

Many of the same authors have described what has been termed geographical differences in DC prevalence, as the prevalence of the condition has been observed to be higher in Scandinavia, the Netherlands, and the U.K., than in the Mediterranean areas, and to be very low in some African groups. Although thought by some to be uncommon in Asian populations, Egawa et al (1990) reported that the prevalence of Dupuytren's disease among persons 60-69 in the Osaka and Kobe areas of Japan (14.4% among males and 8.1% among females), was similar to that observed among European groups.

5.0 PATHOGENESIS

The pathogenesis of DC remains obscure (Schürch et al, 1990), although it is now established that DC arises in the palmar aponeurosis (Mackenney, 1983). Skoog (1957, 1963) noted that "after more than a century of dispute the cause of Dupuytren's contracture is still being debated". The condition has similarities with wound healing and granulation tissue. Both changes in cell biology and biochemical aspects have been noted. This section is not an attempt to summarize an area that has consumed hundreds of articles; the interested reader is referred to various sources in the bibliography.

The cell that may be important in DC lesions has been termed a "myofibroblast" by some (Schürch et al, 1990); others have suggested the term "tractofibroblast" (Flint and Poole, 1990) to imply the function of contractile cells without implying smooth muscle cells. Schürch et al (1990) concluded that present data do not allow a definitive answer regarding its origin. Myofibroblasts possess both contractile and synthetic features; Schultz and Tomasek (1990) described it as a fibroblast which has altered its cytoskeleton and surrounding extracellular matrix. The altered cytoskeleton of the tractofibroblast "is composed of large bundles of actin microfilaments with associated non-muscle myosin" (Schultz and Tomasek, 1990); these are contractile proteins.

Biochemical changes have been observed including: 1) a change in the type of collagen; whereas normal palmar fascia contains mainly Type I collagen (composing about 90% of skin, tendon and bone), in DC there is an enormous increase in Type III collagen. Type III collagen normally occurs in many tissues as a minor component (about 1-2%) in tendon and normal aponeurosis, increasing to 10-15% in apparently uninvolved tissue in DC patients, 10-20% in nodules and 30-40% in fibrous bands (Bailey, 1990). In addition, the collagen content of the palmar fascia is increased in DC compared with normal controls (Glimcher and Peabody, 1990). 2) There is an increase in total glycosaminoglycans, with shifts in the proportions of its components (a decrease in concentration of hyaluronate). Basically, this involves a shift from non-sulphated to sulphated glycosaminoglycans (Delbrück and Gurr, 1990). Compared to normal palmar fascia, in DC the fascia has an increased proportion of high molecular weight proteoglycan (chondroitin sulphate) and decreased proportion of low molecular weight proteoglycan (dermatan sulphate). These authors lamented that "although a good number of detailed studies have been conducted on biochemical changes in DD, the causes of the disease are still unknown".

Glimcher and Peabody (1990), concluding their chapter on collagen organization, noted that "a careful search of the literature reveals that there is essentially no concrete scientific evidence as to the basic underlying aetiology of DD; why the myofibroblasts form; what causes them to contract; if they do, what the cellular basis is for the resorption of collagen or of new collagen synthesis, and the stimuli which lead the cells significantly to alter the post-translational biochemical reactions in the collagen of the palmar fascia in DD". In wound healing, which resembles DC in some respects, the cells' synthetic functions eventually return to normal, while in DC, the increased turnover of collagen continues.

In describing the palmar lesion at an anatomical level, changes have been noted including (a) fat pads in some cases that are almost totally replaced by fibrosis in the palm; and (b) increased vascularity of connective tissue within fatty loculi (Flint, 1990).

An ongoing controversy among writers concerns the so-called "extrinsic" and "intrinsic" theories of the pathogenesis of DC described by Hueston on several occasions (Hueston, 1985; Flint and McGrouther, 1990). Skoog (1948, 1974) suggested that the strain to which certain elements of the aponeurosis were subjected was essential in the pathogenesis of DC, and that the disease originated in fibrillar ruptures within the aponeurosis. He maintained (1957, 1963) that microruptures and microhemorrhages observed in DC play a role in the condition. Partial ruptures that could be demonstrated in specimens by stretching and hyperextending the fingers of patients were taken to support the notion that moderate trauma could account for the multiple ruptures of the aponeurosis postulated in his hypothesis. Hemosiderin detected by some investigators in the nodules and in terminating fibres in association with the nodules was considered support for Skoog's contention that microruptures within the aponeurosis are an important factor in pathogenesis. Thus, in the light of his observations, Skoog (1963) felt that DC may develop as follows: "minor trauma causes a partial rupture of the aponeurosis, which heals by the formation of connective tissue with consequent scarring and shrinking". However, he admitted that "trauma cannot be the only factor, since everyone is exposed to some degree of trauma.... individual predisposition is an important consideration". This theory has been termed the "intrinsic" hypothesis of longitudinal fibre rupture and considered to be support for microtrauma in occupation as playing a role in the condition. Microvascular changes (occlusions) have been observed in DC (Kischer and Speer, 1984).

On the other hand, Hueston on numerous occasions (1985, 1987, 1990, and others) disagreed, arguing that Skoog's theory cannot explain the onset without local injury apart from disuse and local edema, and the common recurrence of identical tissue after removal of the involved aponeurosis. He based his concept of the "extrinsic" hypothesis on his observations that nodules develop within the subcutaneous space on the anterior aspect of the palmar aponeurosis. Flint and McGrouther (1990) pointed out that the concept that Dupuytren's nodular lesions arise from intrafascial rupture "has been repeatedly criticized [by Hueston] but without any firm scientific rebuttal". Flint and McGrouther (1990) believed "that no distinction between extrinsic and intrinsic pathogenesis should be made since the hypodermal connective tissues are anatomically and functionally inseparable from the fascial continuum".

Finally, recent studies examining lymphocytes have suggested the possibility that DC is a T-cell medicated autoimmune disorder (Baird et al, 1993). A successful response to topical corticosteroids reported by Shelley and Shelley (1993) suggested that the local immunological inflammatory change triggered by DC can be suppressed.

6.0 ASSOCIATIONS WITH OCCUPATION (MANUAL WORK/ VIBRATION)

As noted above, this has been considered in two aspects: 1) associations with chronic manual, repetitive work or vibration; and 2) associations with single injury (trauma). The major concentration on epidemiologic review of studies is for the former aspect. Associations with single injury will be discussed in Section 7.0. Several authors have pointed out the confusion with terminology, especially with respect to "trauma". An attempt will be made to limit the term "trauma" to refer to sudden injuries, as opposed to manual (repetitive) work activities.

6.1 The scene

As Hueston (1987) noted "It is natural to assume that a lump in the palm has been caused by the use of the hand". Archer (1992) ably summarized the problem in a section of her Background Paper on Dupuytren's Contracture entitled "The Essence of the Dispute". She pointed out that claims for DC are consistently denied by the Workers' Compensation Board, although the Workers' Compensation Appeals Tribunal (WCAT) has been inconsistent in its handling of appeals. She noted that, in one case, the WCAT Panel decided "the compensation issue will turn on the specific nature of the medical evidence pertaining to each claim, the occupation in question, the symptoms reported and related matters". Moreover, one must bear in mind that "a careful search of the literature reveals that there is essentially no concrete scientific evidence as to the basic underlying aetiology of DD" (Glimcher and Peabody, 1990, pg 84).

6.1.1 Occupational associations: Historical Perspective

Consideration of the possible association of DC with occupation is certainly not new. Both Smith and Masters (1939) and Bell and Furness (1977) noted that in 1912, a government committee in the United Kingdom examined the possibility of a relationship between trauma and DC and found that there was no conclusive relationship. However, the section of the report extracted by Smith and Masters (1939; reproduced in Appendix 1) does not seem particularly convincing today.

6.2 Search methods

The following strategies and sources were used to identify as many relevant studies and reviews as possible:

1) A Medline computer search was conducted in October 1993 (with key words for search strategy: Dupuytren's contracture and acute injury and cumulative trauma and occupation); a previous search conducted in February 1993 (with key words Dupuytren's contracture and epidemiology) was also forwarded by Carolyn Archer;

2) NIOSHTIC;

3) Another literature search conducted for IDSP forwarded by Carolyn Archer;

4) Occupational Medicine texts;

5) Books on Dupuytren's Contracture;

6) References in review articles/ books were examined;

7) Index Medicus was searched manually by this writer for 1990, 1991, and 1992, and monthly supplements for current year through October 1993.

Original epidemiologic articles that were considered to examine the association of DC with manual work and vibration are summarized in detail in Section 6.6.

6.3 Limitations of previous investigations of this condition

On examining the available reviews and investigations, a number of problems and limitations became apparent:

1. In no epidemiological study, was it mentioned whether or not, examiners of hands for physical findings (in cross-sectional studies) were blind to exposure status, or whether assessors of exposure (in case-control studies) were blind to disease status. As will be discussed, this permits an important potential for bias.

2. The difficulty in diagnosing DC has been discussed. The prevalence (or diagnosis) depends on what criteria are used. In particular, as McFarlane (1990) pointed out "patients with DD who consult a surgeon do not necessarily reflect the features of this disease in the general population..." and "when studying associations between DD and other diseases, surgeons should be aware that those patients who require surgical treatment for DD represent a small percentage of the Dupuytren's population" (Hurst and Badalamente, 1990, pg 260). Comparisons of surgical patients to the general population or within subsets of surgical patients may not be meaningful in examining etiology.

3. There have been other methodologic problems with past studies, such as those pointed out by Thomas and Clarke (1992): (i) using selected populations; (ii) not separating the genders; (iii) not stating age distributions; and (iv) not including all stages of Dupuytren's contracture.

4. Overtones of concern over compensation have flavoured some writings. As Flint and McGrouther explained (1990, pg 285):

"It is our belief that there has been some resistance to the acknowledgement of the role of intrafibrillar rupture in the pathogenesis of the Dupuytren's process for fear that if a causal relationship between trauma and DD was established and recognized, there would be a plethora of legal claims attempting to prove that DD has been caused by damage to the hands at work."

They feel that whereas a few cases may show an undoubted causal relationship to the type of work, they go on to say that one should look at out-of-work activity as well. In their discussions of the medicolegal issues, Hueston (1987) and Hueston and Seyfer (1991) focus on the "diathesis" as described above, emphasizing that to assess the diathesis in each patient it is necessary to study a number of factors: ..."the racial origin is of importance" but "a family history is only useful if positive", and "Thus, when a patient asks now 'Why have I got it?', we should simply tell the patient that he or she was 'born to get it!' " In other words, one gets the impression from these authors that whenever DC occurs it is due to the diathesis rather than external factors.

5. Problems in interpretation of confounding factors: It is proper to point out the associations of DC with age, sex and other conditions that should be taken into in any examination of the problem. However, it is not correct to dismiss any case that has other associations as unrelated to work. For example, McFarlane (1991, pg 776) maintained that "the presence of diabetes, epilepsy, alcoholism, or any of the factors that increase the diathesis to disease would lower the probability of a causal relationship between DD and manual work or injury". However, in examining grouped data, one would hope that such contributory factors can be taken into account or controlled in the analysis without necessarily excluding such subjects from consideration. An extraneous causal factor will only be confounding if it is also distributed differently between exposure groups. Excluded those with other risk factors would mean, for example, that because smoking causes lung cancer, asbestos-related lung cancer can never occur in smokers. However, studies such as those by Hammond et al (1979) have demonstrated that the relative risk of lung cancer was increased in both smokers and non-smokers, and that there was statistical interaction.

6. Misclassification: McFarlane (1991) noted that epidemiologic studies can be misleading: "it is likely that the disease began many years before a nodule is palpable; manual and nonmanual work is difficult to define; workers change jobs and the nature of jobs may change; and other factors such as hobbies and other manual activities beyond work have to be considered." However, misclassification of exposure, if nondifferential (unrelated to whether subject has disease or not), would tend to diminish any associations observed, thus diminishing estimated risks toward the null value (or no effect) rather than creating risks that do not exist (Rothman, 1986). If there is differential misclassification as may occur in recall bias with a case-control study, the effect can be to exaggerate or underestimate an effect (Rothman, 1986). This also relates to the advantage of blinding of observers as noted above.

7. There have been problems with terminology. Confusion has arisen over inconsistent use of the term "injury" in some reports, with failure to distinguish between an "injury" and "trauma", the latter used interchangeably with "manual labour" and "repetitive trauma" (Hueston, 1987).

8. Incidence and prevalence are used interchangeably.

6.4 What about the WCAT decisions that have been rendered to date?

Summaries of a number of WCAT decisions considered since 1987 regarding the association of DC with either manual work or previous injuries were forwarded to this writer from the IDSP. Only these summaries were examined; no attempt was made to obtain the full documentation. The following is a partial list of phrases addressing the possible association:

"Although the medical literature was inconclusive as to the cause of Dupuytren's contracture, heavy work and trauma, including microtrauma have been implicated";

"considering medical literature that there was no association with occupation";

"The cause of Dupuytren's contracture has not been identified conclusively but there appears to be a hereditary predisposition to the disease. The treating surgeon related the condition to work. Some medical literature found no relationship to work but some found that the condition could be related to repeated minor trauma";

"There was an inconsistency between the medical evidence in this case (that Dupuytren's disease is not aggravated by work) and the conclusions contained in some prior Tribunal decisions";

"Medical literature was inconclusive regarding a relationship between manual labour and onset or aggravation of Dupuytren's contracture. At best, the literature indicated no greater incidence of the disease in manual labourers tha[t]n in other workers. None of the worker's treating specialists supported a relationship between the worker's work and the onset of the condition";

"There was medical opinion from an expert that there was no evidence that manual work aggravates existing Dupuytren's contracture";

"There was conflicting Tribunal decisions relating to the compensability of Dupuytren's Contracture in similar circumstances. The medical literature on the etiology of Dupuytren's Contracture was also uncertain. The Panel thus required more medical information before it could decide this matter";

"Medical experts are in disagreement as to whether Dupuytren's contracture is causally related to manual labour. The Panel applied the benefit of the doubt and resolved this issue in favour of the worker."

"However, as stated in the medical evidence at hand, there is no relationship between carpal tunnel syndrome and Dupuytren's Disease...The Panel finds no causal relationship between the worker's Dupuytren's contracture and his employment".

The workers appealing their cases to WCAT were employed in a variety of industries/ occupations (Table 4) which may be clues to high risk groups. Of note, at least four were from the automotive industry.

6.5 Summary of previous articles and reviews

6.5.1 What do occupational medicine texts say?

The indices of major occupational medicine textbooks were examined for mention of Dupuytren's contracture. Of eight texts reviewed, there was no mention of DC in the index of five texts (Waldron, 1985; Weeks, Levy and Wagner, 1991; Levy and Wegman, 1988; Zenz, 1988; Rom, 1992). Rosenstock and Cullen (1986) noted that the results of investigations of the possibility that single injuries or recurrent palmar trauma from manual labour is associated with the condition have been mixed and that the "roles of work and trauma are unclear". Gavrilescu (1983) noted that although the etiological conditions are complex, there is "in certain cases a clear correlation between the nature of the subject's work and the appearance of the disease".

Hunter's Diseases of Occupations (Raffle et al, 1987) did not include DC in the index but an earlier edition (Hunter, 1978) in reviewing occupational disorders due to the handling of vibrating tools, included among the section "injury to the soft tissues of the hands" that one could observe "injury to the palmar aponeurosis, and perhaps the onset of Dupuytren's contracture". In a recent guide on hand-arm vibration (HAV) by world-renown authorities (Pelmear et al, 1992; pg 35), the chapter entitled "Clinical Picture (Vascular, Neurological, and Musculoskeletal) under the section "Repetitive Strain Injuries", noted that "Dupuytren's disease, a contracture of the fascial components of the lateral aspect of the palm.... is well known to follow a single injury of the palm. The association with HAV-exposure is not conclusive but cases are being reported", referring to the cases reported by Roberts (1981).

Finally, in the chapter dealing with "Occupational Disorders of the Hand and Digits" in a recent book entitled "Occupational Disorders of the Upper Extremity" (Millender et al, 1992), the authors addressed this issue as follows (Simmons and Koris, 1992):

There is a good deal of debate as to whether Dupuytren's disease is causally related to work; obviously, the only possibility would be in the worker who does heavy labor. The authors have some misgivings about including it in this text; however, since a number of insurance carriers do accept workers' claims, it has been included. This is not meant to imply that Dupuytren's disease is definitely work related. At best, the judgement should be made individually. The young worker who has all the parameters of the aggressive form of Dupuytren's mentioned above is not felt to have the work-related disorder. Furthermore, if the disease occurs in the most common group (i.e. over 50-year old men), one would be likely to consider it work related.

6.5.2 Articles focussing on Dupuytren's Disease

Associations with single injury will be considered separately (see Section 7.0). As a start, two editions of a book devoted to DC were examined (Hueston and Tubiana, 1st ed, 1974; 2nd ed, 1985). The section devoted to the association with "trauma" was limited to two pages (Fisk, 1974; Fisk, 1985). In fact, although the title of the chapter changed slightly between editions (from "The relationship of trauma to Dupuytren's contracture" in 1974 to "The relationship of manual labour and specific injury to Dupuytren's disease" in 1985), the content changed barely at all despite much having been published in the intervening period including one of the original articles of best quality (Bennett, 1982). Fisk (1974; 1985) listed the following points against and in favour of Dupuytren's disease being caused by direct trauma to the hand (this probably encompasses both repetitive work as well as single injury):

Against:

1. The condition is not seen any more commonly in manual workers than clerical workers; indeed, it is said to be slightly commoner in non-manual workers. [Added by GML: This depends on which articles are examined; section 6.7.]

2. It appears bilaterally in some 40 per cent of patients and the dominant hand is not more frequently affected than the other. [GML: In fact, it appears to occur somewhat more frequently in the dominant hand]

3. It has a familial incidence and has been reported in identical twins.

4. It is associated with fibrous overgrowth elsewhere, knuckle pads, Peyronie's disease, plantar fascial thickening.

5. Injuries to the palmar fascia are not all followed by Dupuytren's disease, and scarring of the palm, as for instance after burns, never follows the pattern of change and deformity seen in Dupuytren's disease.

6. Hueston (1963) draws attention to the fact that invalids with enforced inactivity of the hand will give a history of the contracture occurring or increasing during their period of immobility.

In favour:

1. It is commoner in men than women.

2. Its incidence increases steadily with age, which may indicate that chronic minor trauma to the hand has a cumulative effect.

3. It appears to be associated with injury to the hand and arm and its complications, namely Sudeck's dystrophy, tennis elbow, and frozen shoulder.

A more recent book on the subject (McFarlane et al, 1990) devoted much more attention to the subject at hand with separate chapters addressing manual work and industrial injury (Meagher, 1990) and single injury to the hand (McFarlane and Shum, 1990). The latter will be addressed in Section 7.0 of this report.

Meagher (1990) described his chapter as a "personal commentary". To begin, he summarized the results of a questionnaire survey on the relationship of manual work and industrial injury to Dupuytren's disease distributed to the International Federation of Societies for Surgery of the Hand and one member from each of the U.S. states of the American Society for Surgery of the Hand. The results can be summarized as follows:
TOPIC AGREED DISAGREED NO OPINION
DD can be work-related and sometimes qualifies for compensation 28 28 2
DD can be caused by the trauma of work 9 46 3
Prolonged forceful use of tool handles can aggravate DD 31 24 3
Repetitive trauma such as pounding with the hand, holding a stenographic pad or a hand tool can produce DD at the point of contact with the hand 7 45 6

Meagher (1990) considered that there was a logical basis for the support for the third topic because the longitudinal bands of the palmar aponeurosis lie superficial to the flexor tendons, exposing them to pressure from outside. The rigid unyielding flexor tendons and metacarpals beneath do not significantly cushion or absorb pressure from tool handles. He felt that pistol-grip pneumatic tools that resulted in constant compression of the palm, with the added factors of vibration and torque, have an "aggravating effect upon established contractures". Other tools were also thought to have an effect. He referred to the findings of occluded microvessels in DC reported by Kischer and Speer (1984), and taken together he considered the evidence to support Skoog's (1957) belief summarized earlier that manual labour may result in damage to the palmar fascia resulting in microtears and hemorrhages. There seemed to be support for the possibility that work aggravated rather caused the condition. Meagher (1990) concluded this chapter stating that he believed:

that "acceptance of a genetic predisposition in most cases is warranted. It would be premature to state that in every case a genetic link is an essential factor. Certainly the histological findings of Skoog and ...[others] indicate that microtrauma and repetitive digital flexion and extension may play a definite role in the formation of contractures and knuckle pads. The tissues of DD are no less susceptible to the aggravating effects of heavy manual work and selected hand tool designs than other soft tissues. The presence of tenderness in an established contracture should be considered a physical sign of aggravation when combined with an appropriate history of proximate cause. Patients with such a finding should not be deprived of compensation in jurisdictions which consider aggravation of a pre-existing condition a complaint worthy of compensation."

Miscellaneous comments on this subject in this book (McFarlane et al, editors, 1990):

In the section on "The genesis of the palmar lesion" (Flint, 1990) described the normal palm and the load bearing and mobility of the subcutaneous structures, plus the changes that are seen including fibrotic replacement and increased vascularity. The author believed that the palmar lesions of DD arise as a direct consequence of the biological responses, in which the tissues and collagen fibres become less compliant and stiffer, more vulnerable to vertically applied compressive and shearing loads, and more likely to sustain stress or fatigue fractures and cracks, "especially when the longitudinal bands are repeatedly flexed by the impact loading".

McFarlane (1990a) noted that the fact that, as in the palm, only certain components of the finger fascia become diseased, suggested that biomechanical forces play a role; i.e. the fascia from which these cords arise is present bilaterally but "invariably the diseased cord appears only on one side. This is another observation that supports the view that biomechanical forces contribute to the progression of disease". Moreover, in their analysis of the epidemiology of surgical patients (McFarlane et al, 1990a), the authors noted that most patients had disease in both hands but when the disease was unilateral, the right hand was involved almost twice as often as the left. The authors felt that "this observation suggests that the use of the hand or injury may play a role in the development of disease".

However, in an another chapter in the same book, McFarlane (1990b) downplayed the role of biomechanical stress upon the collagen, stating that while it may contribute to propagation of the disease "it is difficult to assign a principle aetiological role to this process. Presumably, disruption of fibre bundles is an everyday event, but not every disruption of fibre bundles progresses to the formation of a pathological nodule. Everyone uses and abuses their hands and yet few develop DD."

In his chapter "Dupuytren Diathesis", Hueston (1990), addressed occupational factors, emphasizing the following:

That the diathesis over-rules any claimed local hand activity is confirmed by:

1. The fact that there is no relation between disease and handedness.

2. The fact that the workers are often aged 50 or older when DD is first noticed; this is normal in the natural history of the disease.

3. There may be racial groups in a job, such as Dutch or German stock in a brewery business or migrant labourers from Scotland and Ireland in Australia. Vibrating tools have no relation to DD. [GML: Some studies contradict this]

Interpretations of the frequent occurrence of DC on the ulnar side of palm:

Some writers have noted that a feature against an association with manual work is the fact that DC most frequently occurs on the ulnar border of the hand which is the "segment of the palm least concerned with manual effort and the area most protectively folded upon itself in grasping and other motions" (Moorhead, 1953). Yost et al (1955) examined a series of DC cases and made similar observations against a work relationship because the left hand was affected to the same degree as the right. They felt out that if "trauma" were an important etiologic factor, one would assume that the incidence of involvement would be greater on the fingers of the right hand. Moreover, they pointed out that callosities, which represent areas of greatest friction or exposed to greatest amount of trauma, are found over "the heads of the metacarpals and over the radial aspect of the middle phalanx of the middle finger, which are not the areas where DC originates". On the other hand, Skoog (1957) commented that the ulnar part of the aponeurosis is where the greatest strain occurs in grasping and passive support.

6.5.3 Summary: One gets the impression from the above articles, that in the context of whether DC might being work-related, the possibility is either dismissed as due to an inherited diathesis, or at most, only results in aggravation of pre-existing lesions. The frequent bilateral occurrence, and positive family history among affected subjects are often cited as evidence against a relation with work. There are suggestions that judgements "should be made individually" much as WCAT is doing now. Original studies showing a "positive" association, such as Bennett (1982), tend not to be referenced. What do the original studies show?

6.6 Methods for Consideration of Original Articles

Types of Epidemiologic Study Design

The different types or designs of occupational epidemiologic studies can be considered to follow a "hierarchy" of decreasing "quality" (Ontario Advisory Council on Occupational Health and Occupational Safety, 1983; Rothman, 1986):

Randomized controlled trial

Nonexperimental studies:

Follow-up (Cohort) Studies

Prospective Cohort Studies

Historical prospective cohort studies

Case-control studies

Proportional mortality studies/ cross-sectional studies (which are varieties of case-control studies; Rothman, 1986)

Case series, case reports

These have usually been addressed in the context of mortality studies. In the current context of morbidity assessment, there are, of course, no RCTs, and cross-sectional studies form the majority of available reports.

Identification of Relevant Studies

The search strategy listing the possible sources was given above (Section 6.2). Original studies were chosen for more detailed review if their titles (and/or abstracts if available) met the following criteria: 1) published in English (if not in English, if English summary was available, it was examined and if suggestive that it met these criteria, article sent for translation); 2) Dupuytren's Contracture was an outcome identified (cases of DC having operations were not included even if compared to control group); 3) they were conducted in one or more working populations (or if population-based, then comparisons of manual vs non-manual); 4) the group of interest had exposure to manual or repetitive work, or vibration; 5) the study design was case-control, cross-sectional, longitudinal cohort, or randomized controlled trial (RCT) (case reports and case series without controls were not included).

Selection of studies

Possibly relevant studies were retrieved, and the following inclusion criteria were used, adapted from those used by Stock (1991) in her overview of ergonomic factors in the development of musculoskeletal disorders of the upper extremity:

population: exposed and control working population(s) were defined (or population-based community study). (For the study by Hueston (1960) who examined various patient groups as well as working groups, only the latter were compared.)

exposure: in general for the available studies of DC, assessment of exposure was limited to job title (e.g. groups were assigned to manual work or vibration or non-manual).

outcome: in general, assessment of outcome for the available studies was limited to mention of Dupuytren's contracture (yes or no); in some cases, explicit staging of disease was indicated.

study design: comparative studies, i.e. case-control, cross-sectional, cohort, RCT.

Assessment of Validity of Studies

Most of the controlled studies included based on the selection factors above were cross-sectional in design. There have been fewer attempts to develop criteria for these than for mortality studies. The quality of the studies examining the association of DC and manual work/ vibration was assessed using a series of questions adapted from that used by Stock (1991) in her assessment of ergonomic factors in musculoskeletal disorders of the upper extremity. The list of questions used in this assessment are provided in Appendix 2. An attempt was made to assess validity using the seven criteria utilized by Stock (1991): absence of selection bias, absence of nonrespondent bias, comparability of study and control groups, accounting for confounders, validity of exposure measures, validity of outcome measures, and blinding of assessors. However, there was limited information available for many of the criteria in most studies. The intraobserver and interobserver consistency of these criteria was tested by the author repeating the rating blind to the first assessment and by having a second observer independently rate the studies. Agreement was calculated using the kappa statistic (Sackett et al, 1985).

Stock considered that the three criteria that posed the greatest threats to validity were comparability of the groups and validity of exposure and outcome measures (items 3, 5 and 6 in Appendix 2). She decided, prior to the assessment, that if any study had major flaws (i.e. score of 1) in any of these areas, the "validity of the results of that study would be seriously compromised".

Presentation of Findings of Studies

For the studies that could be assessed, odds ratios and 95% confidence intervals were calculated using True Epistat (Epistat Services, 1989). The author did not consider there to be sufficient similarity among studies to justify aggregating the results.

6.7 Results of evaluation of original investigations

6.7.1 Selection of Studies

From the many potentially relevant studies, six English language studies (seven papers) were identified that met the above criteria. A seventh study, by Bergenudd et al (1993), included the findings of a population-based general health survey in Malmo, Sweden, to which a physical examination with attention to the occurrence of DC had been added. Information on occupation was recorded; the authors indicated that "there no difference in occupational work load ... between subjects with and those without Dupuytren's contracture" but presented no data. Six potentially relevant studies in other languages were identified, and were translated; three met the criteria. Case series and surgical series not meeting the criteria are listed in Appendix 3.

Of the six English studies (Herzog, 1951; Hueston, 1960; Early, 1962; Mikkelsen, 1978, 1990; Bennet, 1982; Thomas and Clarke, 1992) that met the inclusion criteria, five were cross-sectional; Mikkelsen's study was a population-based survey of a Norwegian town, one component of which included examination of all inhabitants older than 16 for Dupuytren's disease. Table 5 outlines the main features of these studies, and Table 6 summarizes their results. Table 8 summarizes the translated articles and the results are included in Table 6.

6.7.2 Validity Assessment of Studies

The validity assessment of the English studies as determined using the form in Appendix 2 is presented in Table 7 with relative ranking of studies according to methodologic quality. The kappa for inter-observer rating was 0.54, and for intra-observer rating was 0.65 indicating moderate agreement.

The quality (ranking) is rather poor (median rank 11, range 8-14) out of a potential score of 22. In particular, no articles stated that there was blinding of examiners, and "exposure" was often little more than job title. If one restricts consideration to studies with scores of 2 or more on the three criteria of comparability of groups, valid exposure measures, valid outcome measure, only those by Bennett (1982) and Thomas and Clarke (1992) remain.

6.7.3 Study findings

Manual work: Two studies found no association with DC (Hueston, 1960; Early, 1962; Bergenudd et al, 1993 may represent a third but no data were presented), one found a weak non-significant association (Herzog, 1951; OR 1.2-1.3), while two found significant positive associations: Bennet (1982) observed a standardized morbidity ratio of 1.96 among bagging and packing plant workers compared to the expected prevalence given by Early (1962) and an OR of 5.5 compared to a local plant without bagging and packing. From the data of Mikkelsen (1990), gender-adjusted Mantel-Haenszel ORs of 3.1, 2.7, and 2.0 were computed for heavy, medium and light work, respectively compared to non-manual work; there was a was a significant "dose-response" relationship.

Vibration: Thomas and Clarke (1992) found that DC was observed 2.1 times as frequently among vibration-exposed claimants with vibration white finger (VWF) than subjects being admitted to hospital for surgery. Cocco et al (1987) reported that a history of exposure to vibration at work was more frequently found among cases of DC compared to controls without DC (OR 2.3, 95% CI 1.5-4.4). This effect was unchanged when adjusted for alcohol consumption and the presence of peripheral vascular abnormalities by photoplethysmography. There was a significant dose-response relationship with increasing duration (years) of exposure to vibration (Table 6); a similar result was observed if only miners were considered vibration-exposed (OR 2.1; 95% CI 1.3-3.4). Two other articles (Landgrot et al, 1975; Patri et al, 1982) did not find an association between DC and vibration exposure but the control groups consisted largely of "manual" workers.

Causality: Some of these investigations demonstrate a reasonably strong relationship between manual work/ vibration and DC but are these causally related? One can consider criteria to determine causation (for example, Sackett et al, 1985; Rothman, 1986). The strength of the association is moderate to strong (about 2 or more) in 3 of 6 studies of manual work and 2 of 4 of vibration exposure but an association is not consistently seen. For no study, could temporality be determined with certainty, although Cocco et al (1987) did look at duration of exposure. Only Mikkelsen (1990) and Cocco et al (1987) had evidence of a dose-response. No studies attempted to rule out other causes (specificity).

7.0 SINGLE INJURY AND DUPUYTREN'S CONTRACTURE

Much has been written about whether DC might arise as a complication of hand injury. That is, those who suffer from DC are apt to blame a single accident (Smith and Masters, 1939). Many case reports have reported cases which followed in time after a single hand injury such as penetrating wounds, crush injuries and fractures (e.g. Hueston, 1962, 1963, 1968) but these were not controlled. Hueston (1968) presented data showing that among a series of DC cases, there was a much higher proportion associated with a hand injury in the younger age groups compared to that among older cases; Hueston himself described this as "circumstantial".

In general, authors have been more accepting of this association with DC than with chronic manual work, including Hueston (1987) who stated "It is commonplace to see Dupuytren's contracture first appearing in the palm of an elderly woman soon after the removal of a plaster cast for a Colles' fracture".

However, some caution is needed in interpreting this for 2 reasons: first, among some of the groups affected, such as the elderly referred to above, DC is common in general (prevalence approaching or exceeding 10%); second, the impressions are anecdotal. Ideally, in order to assess this association epidemiologically, one would compare (prospectively) the occurrence of DC among a group who had sustained a (single) hand injury with that among a group who had not sustained such an injury. [Alternatively, one could compare the prevalence of past hand injury among those with and without DC.] To my knowledge, no such data are available. Despite this, there appears to be more widespread agreement about the relationship with single injury than with manual work.

As we will see, a complementary approach, the past history of single injury among those DC cases coming to surgery (McFarlane et al, 1990a), has been analyzed. Although interesting, this does not necessarily give a valid picture of all those injured or all DC cases; and one is left to interpret anecdotal reports only. However, these surgical findings will be reviewed for completeness as it represents one attempt to characterize this association.

As part of their survey of 1150 surgical cases of DC (McFarlane et al, 1990a), these investigators asked a question about a history of a single injury associated with the onset of DC. The findings have been summarized by McFarlane and Shum (1990). Within this surgical series, variables that were significantly associated with the patient relating "a single injury to the onset of disease" included male gender, age at onset if male less than 45 years, manual labour, unilateral disease, and one ray involved. They noted that "this analysis identifies a group of young male labourers in whom a single injury to the hand may have precipitated the appearance of rather mild disease".

They then further reviewed 309 totally documented cases to select patients in whom a close relationship between a single injury and the onset of DC was likely. Based on the following criteria: 1) history of single injury to the hand; 2) objective evidence of tissue damage, such as scarring or healed fracture; and 3) DC in the area of injury, they identified 18 potential patients who had a palpable nodule or cord in the area of the injury. They then attempted to sort these 18 patients into 3 categories: 1) DC related to injury; 2) DC not related to injury; and 3) not DC, based on the clinical assessment, course of the disease, and particularly the pathological report.

These investigators (McFarlane and Shum, 1990; McFarlane, 1991) pointed out that "microscopically, distinguishing between scar tissue resulting from trauma and DD may be difficult" but they provide a list of histopathological differences between DC and scar tissue due to trauma. Ultimately, 7 of the 18 patients were considered to have Dupuytren's disease related to work, each of whom was injured before age 30 (crush injury in 2, laceration in 4, fracture in 1). The reason given for this categorization was "early onset" after injury. McFarlane (1991) indicated that these patients had no disease associated with DC, that none had a family history of DC, or plantar or penile fibromatosis.

Among the 9 considered not to have DC, there was scar contracture as a result of their injury. In 3 of these, the nodule was noted to have "disappeared"; McFarlane (1991) noted this occurred after correction of scar tissue. In some "the tissue thought to be DD was in fact scar tissue". No indication was given regarding the reproducibility of their classification scheme, whether the assessment was done blind to age, or whether, in the end, any factors other than age at injury were weighted heavily. McFarlane and Shum (1990) go on to state:

Thus, to qualify for consideration of an association between a single injury and the onset of DD, the individual must be younger than the usual age of onset (less than 40 years old), be free of epilepsy or diabetes, have unilateral disease and have no ectopic deposits.

The authors conclude that they "have shown that occasionally a single injury can precipitate the onset of DD. Presumably this occurs in genetically susceptible individuals" but that the causal relationship can only be established in young people. They did note that "the mechanism by which DD is precipitated by injury is not explained by our studies". To their credit, they emphasize that it "would be helpful to compensation agencies and fairer to workers and employers if criteria were established to serve as guidelines when establishing a relationship between a single injury and the onset of DD." To this end, they suggested the following guidelines:

1. The appearance of DC before age 40 in men and 50 in women suggests a causal relationship unless the individual expresses a strong diathesis such as the presence of epilepsy, diabetes, bilateral disease or ectopic deposits.

2. If the DC is bilateral, the disease in the uninjured hand should have appeared after age 40 in men and age 50 in women.

3. The injury was within the hand.

4. There is objective evidence of injury.

5. DC is in the area of the injury in the hand.

6. DC appeared within 2 years of injury.

7. Histological proof of fibromatosis is needed to make a definite diagnosis of DC.

This writer is not qualified to comment on the histopathological aspects that might differentiate DC from scar tissue. Their guidelines should be welcomed as a starting point as they are the first attempt to bring some structure to the discussion. However, I have some difficulties with at least two of these criteria. First, the 2 year rule: It is my understanding that DC has a variable course, and as noted above, some authors have described the difficulty in determining the onset because the patient may be asymptomatic in the early stages. For example, McFarlane (1991) himself pointed out that it is difficult to diagnose DC when the nodules are small, and that "it is likely that the disease began many years before a nodule is palpable". Thus, the onset may be uncertain. Nodules may be present for some time (perhaps even beyond 2 years post-injury) before cords or further thickening or contracture cause the patient to seek medical assistance. Moreover, it is of interest that the interval between injury and onset of DC was 5 years in one of the 7 patients in the definite Dupuytren's disease related to injury category of McFarlane and Shum (1990) (Patient SG in their Table 25.3)!

Second, the 40 year age rule: Similarly, it is not clear how one can differentiate the "injury-relatedness" of a case of DC arising within an "acceptable" time period after injury (say 1.5 years), at an "acceptable" location (the same area as the injury), in a 35-year old worker from the same sequence of events arising in a 50-year old. An analogy can be made to the association between lung cancer and asbestos exposure, according to smoking status as shown below:

Syngergistic Effect of Smoking and Asbestos Exposure on Lung Cancer
-------------------------------------------------------------------
                    Exposure        History         Mortality
Group               to Asbestos     Cig Smoking     Ratio
--------------------------------------------------------------------
Control             No              No              1.00
Asbestos Workers    Yes             No              5.17
Control             No              Yes             10.85
Asbestos workers    Yes             Yes             53.24
--------------------------------------------------------------------

Source: Hammond EC, Selikoff IJ, Seidman H. Ann NY Acad Sci 1979;330:473

Here, the risk of lung cancer due to asbestos exposure is increased in both smokers and non-smokers. Thus, it may be that the relative risk of DC is increased following a single injury to the hand, perhaps by a similar factor at different ages, despite the changing underlying risk of DC. It may be that data do not exist at present to test this hypothesis.

8.0 DISCUSSION AND CONCLUSIONS

This discussion section will not be detailed because many of the points of view from different writers have already been reviewed in Section 6.5. To began, it appears that the inconsistent findings of WCAT panels (as summarized in Section 6.4), in which the decision is made for or against different workers with similar histories depending on which "expert" is giving evidence does not appear to be fair. Next, let us summarize the separate scenarios for Dupytren's contracture: (1) with manual work; and (2) with single injury.

Manual work/ vibration:

Herzog (1951) noted three possible relationships to work: (1) DC "is always caused by hard work; (2) it is never caused by hard work; or (3) hard work is a contributory cause".

The possibility that DC is work-related has been largely ignored in the occupational medicine literature. This does not mean that manual work might not be contributory. On the other hand, the literature examined in Section 6 above focussing directly on DC has a strong surgical perspective, which is not unreasonable given that these specialists assess and treat many DC patients. One gets the impression from these writers that the possibility that DC might be work-related is dismissed as due to an inherited diathesis (noting the frequent bilateral occurrence and familial clustering), or at most, that work can only can lead to aggravation of pre-existing lesions. It is not made clear, however, how one could identify the pre-existing lesion in the absence of previous surveys or examinations.

Moreover, it is interesting that these writers repeatedly refer to the negative or weakly positive studies that support their position (such as those by Herzog, 1951; Hueston, 1960; Early, 1962) while first, consistently failing to include in their reviews the ("positive") study which had the highest ranking (Bennett, 1982). Second, they have criticized the other "positive" report by Mikkelsen (1978) (for example, see Hueston, 1985) because occupation was obtained for only about 11,000 of the almost 16,000 subjects in the initial Norwegian report; however, in the more recent update Mikkelsen (1990) included occupation for over 13,000 residents. In fact, this writer wrote to Dr. Mikkelsen on November 16, 1993 asking about the missing occupations in the 1978 paper. He replied on November 29, 1993 that the original numbers were in error; the 1990 data are correct (his letter is shown as Appendix 4). Third, one must keep in mind the methodological limitations and anecdotal nature of much of this writing, as was emphasized in Section 6.3.

How about the original epidemiologic studies? The critical appraisal of the existing original studies (Section 6.7) shows that they are mostly cross-sectional in design. Cross-sectional studies in general are inherently limited for a number of reasons. For example, there may be "survivor bias" (those who have developed disease may have left the work force, leading to an underestimation of risk among those presently employed). Second, prevalence data, when exposure and disease are obtained at the same time, cannot easily be used to determine cause and effect relationships. In addition, the studies available are of rather poor quality: in none, were examiners of hands for DC blinded to exposure status; and there is essentially no quantitative description of exposure in these studies, with respect to force, frequency, and vibration (merely job title). Moreover, only for the studies by Bennett (1982) and Thomas and Clarke (1992) were the ratings 2 or more for the 3 criteria suggested by Stock (1991) as posing the greatest threats to validity.

With these weaknesses in mind, taken together the available studies suggest that whether DC can be related to manual work is uncertain. Evidence supporting an association with manual work is seen in some studies but not in others; the associations seen could be due to bias, confounding or chance. A major impediment is the absence of quality studies, as "no epidemiological study has yet been precise enough to separate and define the roles of age, inheritance, and hand usage in the pathogenesis of DD" (Flint and McGrouther, 1990). For the small number of rated studies, the quality (as estimated by the rating) appeared to improve over time (Spearman rank correlation coefficient, rs=0.85, p=0.03, n=6), as did the strength of the association (OR) (rs=0.77, p=0.07). In turn, the ORs were moderately correlated with the rating (rs=0.53, p=0.28), suggesting that, as the quality improved, a stronger association was observed. The study by Bennett (1982) which appears to have the greatest quality showed approximately a doubling of observed cases, compared to the expected prevalence. The association cannot yet be considered causal but needs to be confirmed elsewhere.

Although Skoog (1963) conceded that "there is conclusive evidence that a hereditary predisposition plays a role in the etiology of the disease", he went on to state "but this does not mean that environmental factors do not also play a part". It is likely, as Flint and McGrouther (1990) stated that "the pathogenesis ... has a multifactorial basis over a prolonged period of time".

Vibration:

Many of the comments discussed above apply to that subgroup of manual work involving vibration exposure and its possible association with DC. There is some evidence supporting this association from two studies that considered vibration (Thomas and Clarke, 1992; Cocco et al (1987), while others did not. However, these data should be interpreted with caution for two reasons: first, the study group examined by Thomas and Clarke (1992) was not, strictly speaking, one with vibration exposure per se but rather a subgroup of the vibration exposed population that developed VWF. Those developing VWF may differ from other vibration-exposed subjects (and controls) in some way that may also be associated with the development of DC. Second, because the control group in this study was drawn from patients being admitted to hospital, the location for them was no doubt different than that for the controls. Thus, lack of blinding of examiners in this case was perhaps even more obvious than in other studies. On the other hand, it is possible that the inclusion of "manual" workers among the control subjects in this report and those of Landgrot (1975) and Patri (1982) may have diluted or masked the association.

The suggestive findings in the studies by Thomas and Clarke (1992) and Cocco et al (1987) are supported by cases reported by Roberts (1981) of two men who developed DC after 4.5 to 5 years vibration exposure on a grinding wheel while removing deeply imprinted lettering from metal starter yokes; none of six other, lesser exposed employees exposed for periods from 2 months to 5 years showed evidence of DC. Dr. William Taylor, a world expert on HAV, noted (1988) that "it is probable that heavy manual work involving heavy hand-held tools will produce some joint deformation with the gradual onset of contracture of the palmar aponeurosis (Dupuytren's contracture)... These signs are found in long-term (20-40 years) pneumatic drill operators and suggest direct mechanical trauma. Present evidence points to vibration being a possible but small aggravating factor". This conclusion is also consistent with the findings reviewed here. However, if the association is, in fact, causal, it is not clear how one differentiates initiating from aggravating factors.

It is of interest, as noted previously, that many of the recent WCAT cases have occurred in the auto sector; whether this is due to increased awareness among the workers or represents true "clusters" of excess incidence is unclear.

Single injury:

There appears to be more acceptance in the surgical literature of the association of DC following a single injury. However, this reviewer has some concerns as discussed because there are no data directly comparing the incidence (or even prevalence) of DC among those suffering and not suffering hand injury. On the other hand, the microscopic similarities between DC and wound healing, and the obvious stimulus to the fibroblasts (or myofibroblasts) after trauma make a strong case for biologic plausibility.

The guidelines proposed recently by McFarlane and Shum (1990) for establishing a relationship between a single injury and the onset of DC represent a reasonable first attempt but as indicated above the age and "latency" requirements need further discussion. In particular, the inconsistency with respect to the acceptable latency interval between the single injury and the occurrence of cases of DC related to injury between their guideline and a case in these authors' own writing needs to be clarified.

9.0 RECOMMENDATION

Although this reviewer was not asked to make specific recommendations, the following are offered:

1. Additional studies of better quality are required to further explore the association of DC with 1) manual work, 2) vibration, and 3) single injury in order to refute or provide further evidence to support these hypotheses. It may be possible to conduct new morbidity studies with improved methodology relatively quickly. This author would be willing to discuss with the Panel how these might be designed.

2. The guidelines for single injury and DC proposed by McFarlane and Shum (1990) might be adapted in the interim.

3. The inconsistency shown in WCAT appeals has been unfair to workers. Workers with "equivalent" past exposures and similar temporal sequences in the development of DC, should be handled by the "system" in a similar manner. The decision to allow appeals in some cases and not others should not depend only on which medical expert happens to be providing evidence.

ACKNOWLEDGEMENTS

Ms. Carolyn Archer at the IDSP provided helpful initial material and obtained translations of some articles. Ms. Marlene Vaz helped in the preparation of the tables. The validity assessment approach developed by Dr. Susan Stock was adapted for examining the studies; she also rated the studies independently.

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Schultz RJ, Tomasek JJ. Cellular structure and interconnections. In: McFarlane RM, McGrouther DA, Flint MH, editors. Dupuytren's disease: biology and treatment. New York: Churchill Livingstone, 1990:86-98.

Schürch W, Skalli O, Gabbiani G. Cellular biology. In: McFarlane RM, McGrouther DA, Flint MH, editors. Dupuytren's disease: biology and treatment. New York: Churchill Livingstone, 1990:31-47.

Shelley WB, Shelley ED. Response of Dupuytren's contracture to high-potency topical steroid (letter). Lancet 1993;ii:366.

Simmons BP, Koris MJ. Occupational disorders of the hand and digits. Chapter 10. In: Millender LH, Louis DS, Simmons BP, eds. Occupational Disorders of the Upper Extremity. New York: Churchill Livingstone, 1992: pp 105-115.

Skoog T. Dupuytren's contraction. Acta Chir Scand 1948;96:Supplement 139:1-190.

Skoog T. Dupuytren's contracture. Postgraduate Medicine 1957;21:91-99.

Skoog T. Dupuytren's contracture: pathogenesis and surgical treatment. In: Hueston JT, Tubiana R, editors. 1st English ed. London: Churchill Livingstone, 1974:109-117.

Skoog T. The pathogenesis and etiology of Dupuytren's contracture. Plastic & Reconstructive Surgery 1963;31:258-267.

Smith KD, Masters WE. Dupuytren's contraction among upholsterers. J Ind Hyg Toxicol 1939;21:97-100.

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Taylor W. Biological effects of the hand-arm vibration syndrome: Historical perspective and current research. J Acoust Soc Am 1988;83:415-422.

Viljanto JA. Dupuytren's contracture: a review. Seminars in Arthritis and Rheumatism. 1973;3:155-176.

Waldron HA. Lecture notes on occupational medicine. 3rd ed. London: Blackwell Scientific Publications, 1985.

Weeks JL, Levy BS, Wagner GR, editors. Preventing occupational disease and injury. Washington, DC: American Public Health Association, 1991.

Yost J, Winters T, Fett HC. Dupuytren's contracture: a statistical study. Am J Surg 1955;90:568-571.

Zenz C, editor. Occupational medicine: principles and practical applications. 2nd ed. Chicago: Year Book Medical Publishers, Inc, 1988.

TABLE 1

RATIO OF MEN TO WOMEN IN THOSE WITH DUPUYTREN'S CONTRACTURE, BY AGE
Age (years) Men (%) Women (%) Ratio of men:women
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-89
0.19
0.38
0.23
1.08
2.50
4.95
9.95
14.42
21.87
27.01
36.67
33.66
32.99
30.77
0
0
0
0
0.29
0.95
1.73
2.28
3.74
8.00
13.45
16.48
17.78
25.00
-
-
-
-
8.4
5.2
5.8
6.1
5.8
3.4
2.7
2.0
1.3
1.2

TABLE 2

NUMBER OF MEN WITH DUPUYTREN'S CONTRACTURE (DC), BY AGE AND HAND
Age (Years) Number DC Right Left Both
20-29
30-39
40-49
50-59
60-69
70-79
80-89
90-99
1061
905
1288
1361
946
475
113
2
3
6
50
163
228
168
28
1
0
2
19
47
61
34
5
1
2
1
6
31
27
28
3
0
1
3
25
85
140
106
20
0
Total 6151 647 169 98 380

TABLE 3

NUMBER OF WOMEN WITH DUPUYTREN'S CONTRACTURE (DC), BY AGE AND HAND
Age (Years) Number DC Right Left Both
20-29
30-39
40-49
50-59
60-69
70-79
80-89
90-99
1510
1184
1650
1758
1320
667
171
10
0
0
11
35
76
98
33
1
0
0
5
22
30
26
11
0
0
0
6
8
14
18
4
0
0
0
0
5
32
54
18
1
Total 8270 254 94 50 110

Source for all 3 tables: Mikkelsen (1990)

TABLE 4

OCCUPATIONS/ INDUSTRY OF SOME CASES COMING TO WCAT
Air gun operator

Assembly line worker - tightened bolts with air gun

Automobile assembler line

Automobile assembly line

Automotive industry - assembler; vibrations (tools)

Autoworker - repaired trim on bodies

Maintenance mechanic - hammers, sledgehammers, torque wrenches

Mechanic - serviced heavy duty machinery; extensive use of vibratory air tools


TABLE 5

SUMMARY OF STUDIES ON MANUAL WORK/VIBRATION AND DUPUYTREN'S

CONTRACTURE
Herzog Early Hueston Mikkelsen Bennett Thomas and Clarke
Country (Year) U.K. (1951) U.K. (1962) Australia (1960) Norway (1978, 1990) U.K. (1982) U.K. (1992)
Design Cross-sectional Cross-sectional Cross-sectional Population-based survey Cross-sectional Cross-sectional
Study Subjects 503 Steelworkers

> 40

451 miners > 40

4454 Male manual workers at locomotive works (4375 < 65) 530 Male brewery workers 477 Males, 6 females in heavy work; 2304 males, 4710 females in medium work; 2285 males, 707 females in light work 216 Workers at PVC bagging and packing plant 500 Claimants considered to have Vibration White Finger (VWF) assessed 1988-1990 (311 aged 50-85)
Control Subjects 480 clerks > 40 427 Male office workers at same locomotive works (426 < 65) 550 Male office workers 1805 Males, 1104 females in non-manual work 1) 84 Workers at another plant with no bagging or packing;

2) also compared to prevalence among male workers (clerical & manual) from Early (1962)

150 Consecutive males aged 50-85 admitted to Middlesborough General Hospital for elective or emergency treatment to general surgical ward; none had VWF symptoms
Exclusions Not stated Not stated Not stated Response rate to survey 71% for males, 82.4% for females;

Occupation obtained only for 13,415 of 15,950 residents examined.

No exclusions at study plant;

Not stated for other plant

None stated
Outcome Presence of DC; no grading system Presence of DCa - system of staging reported DC on examination of hands: thickening in palm either as nodule or plaque/ band accepted Examination of town inhabitants for presence of DC based on finding of nodules DC on inspection of hands; used scheme from Early (1962) Exposed: "All stages of DC from nodule to contracture"

Controls: Examined for presence of DC following admission

Blinding of examiners/ assessors Not stated Not stated Not stated Not stated Not stated No
Exposure Manual vs non-manual (clerks) Manual vs office workers (job title)

by job title

Presumed manual vs office Type of work:

"heavy", "medium".

"light", "nonmanual"

Bagging and packing vs.

1) No bagging and packing

2) Manual & clerical workers at locomotive works (Early, 1962)

asked about types of tools & chemicals handled through career

Vibration exposure vs controls (102 heavy manual labour, 29 clerks & teachers, 19 semi-skilled & unskilled occupations)

Confounders measured Age restriction;

No stratification

Age Age Gender Age, gender

Asked about fam history, past illness, injuries, alcohol

Age restriction
Analysis In original: %,

GML: OR

In original: % (relative frequency in 2 groups)

GMLb: M-H 2, ORc

In original: %

GML: M-H 2, OR

In original: %

GML: M-H 2, OR controlling for age, and gender

% and indirect standardization (morbidity ratio) In original: %, 2,

GML: OR

Conclusion "Slight differences in incidence between clerks and workmen is of no significance" Prevalence of DC no different in manual vs office DC prevalence no higher in brewery workers Prevalence of DC increased with increasing heaviness of work Prevalence of DC increased at bagging and packing plant Prevalence of DC increased in vibration exposed subjects

a DC = Dupuytren's contracture; b GML = calculation by G.M.Liss; c M-H 2 = Mantel-Haenszel chi-square; OR = Odds Ratio

TABLE 6

SUMMARY OF RESULTS OF STUDIES OF MANUAL WORK/ VIBRATION
Rank Study Outcome Odds Ratio 95% CIa p-value
Studies of Manual Exposure
1 Bennett (1982) DCb: bagging plant vs:

non-bagging plant

office & manual locomotive workers (Early, 1962)

5.5

1.96

(Obs 16;

Exp 8.08)

0.8-36.7

1.1-3.3

0.142

0.009

2 Early (1962) DC:

Manual vs clerical

0.98 0.6-1.7 0.984
3 Mikkelsen

(1978, 1990)

DC:

Males

Heavy vs non-manual

Medium vs "

Light vs "

Females

Heavy vs non-manual

Medium vs "

Light vs "

M-H OR adj for genderc

Heavy vs non-manual

Medium vs "

Light vs "

Signif dose-response

3.1

2.3

1.9

21.9

5.4

3.2

3.1

2.7

2.0

2.2-4.3

1.8-2.9

1.5-2.4

0.9-230

2.8-10.9

1.4-7.3

2.2-4.4

2.1-3.3

1.6-2.5

<10-8

<10-8

6x<10-7

0.069

<10-8

0.003

<10-8

<10-8

<10-8

4 Hueston (1960) DC:

Brewery vs office

0.9 0.6-1.4 0.833
5 Herzog (1957) DC:

Steelworkers vs clerical

Miners vs clerical

1.2

1.3

0.6-2.3

0.6-2.5

0.739

0.599

Studies of Vibration
(translated)

(translated)

(translated)

Thomas & Clarke (1992)

Cocco (1987)

Patri (1982)

Landgrot (1975)

DC: Vibration-exposed (VWF) vs hospital admissions

Vibration exposure (DC cases vs controls)

< 10 yr exposure

11-20 yr exposure

> 21 yr exposure

DC: Lumberjacks vs controls (machine shop)

DC: Vibration-exposed vs controls

2.1

2.3

1.7

2.4

3.0

0.9

1.2

1.1-3.9

1.5-4.4

0.9-3.4

1.3-4.2

1.3-6.7

0.5-1.8

0.8-2.0

0.019

0.859

0.393

a CI = Confidence Interval; b M-H OR = Mantel-Haenszel Odds ratio; c DC = Dupuytren's contracture

TABLE 7

VALIDITY ASSESSMENT RESULTS OF ORIGINAL STUDIES

OF MANUAL WORK/ VIBRATIONa

Herzog Hueston Early Mikkelsen Bennett Thomas & Clarke
Population

1. Selection bias

2. Nonrespondent bias

3. Comparable groups

Exposure

4. Confounders

5. Valid exposure measures

Outcome

6. Valid outcome measures

7. Blinding of examiners

Total (out of 22)

1

1

2

1

1

1

1

8

1

1

2

1

1

2

1

9

1

1

3

1

1

3

1

11

2

2

1

1

1

3

1

11

1

2

3

2

2

3

1

14

3

3

2

1

2

2

1

14

a See Appendix 2 for Validity Assessment Criteria

TABLE 8

SUMMARY OF TRANSLATED STUDIES ON VIBRATION AND DUPUYTREN'S

CONTRACTURE
Landrgot Patri Cocco
Country (Year) Czechoslovakia (1975) France (1982) Italy (1987)
Design Cross-sectional Cross-sectional Case-control
Study Subjects 807 workers exposed to vibration

(791 < 65)

107 Lumberjacks exposed to vibration Cases: 180 cases of DC identified from 14,557 clinical files of Instituto di Medicina del Lavoro of Cagliari, 1970-85
Control Subjects 444 maintenance workers and clerical workers 115 Manual workers not using vibrating devices Controls: 180 subjects from same files without evidence of DC, matched with a case by sex, age (± 5 yrs), and hospitalization (± 7 days)
Exclusions Not stated Not stated All cases of contracture included
Outcome Presence of DC; grading not stated Examination of hands (no details or grading system reported) Cases defined by presence of definite contracture (initial stage with only nodules, cutaneous umbilications, isolated palmar fascia thickening or knuckle pads not considered)
Blinding of examiners/ assessors Not stated Not stated (Blinding to case status during determination of exposure): Not stated
Exposure Vibration exposed (pneumatic tool operators, forestry, miners, stonecutters, grinders) vs controls (maintenance workers, lathe operators, machine shop, clerical workers) Vibration exposure (66 of 107 had VWF) vs controls ("manual" workers not using vibrating devices, < 50 hours/ year) Occupational history used to establish exposure to vibration, its duration and tools used during work activity (exposed defined as miners, hammer-drill operators, stone cutters, some construction workers, sawing-machine operators, saw-mill workers, milling or grinding or lapping-machine operators); photoplethysmography of fingers performed to investigate angiopathy by vibrating tools
Confounders

measured

Age No age stratification given; controls recruited so average age similar Age and sex matching;

Alcohol

Analysis In original: %

GML: OR

In original: %

GML: OR

OR, 2 for trend
Conclusion "No substantial difference in incidence of DC between various occupations" Frequency of stage I DC identical among lumberjacks and manual workers; DC similar among lumberjacks with and without VWF Statistically significant increase in risk of DC in workers occupationally exposed to vibration; a dose-response relationship between duration of employment in jobs with use of vibrating tools and risk of DC also observed. Same result observed considering only miners as the exposed group.

APPENDIX 1

Abstract from "Report of Departmental Committee appointed to inquire and report whether the following diseases can properly be added to those enumerated in the Third Schedule of the Workmen's Compensation Act, 1906, namely: (1) Cow pox, (2) Dupuytren's contraction, (3) Clonic spasm of the eyelids, apart from nystagmus, (4) Writers' cramp. London, 1913.

[Source: Smith KD, Masters WE, Journal Ind Hyg Toxicol 1939;21:97-100]

"Any recommendation on the subject of Dupuytren's contraction involves consideration of the question whether other classes of workers than lace operatives should be afforded opportunities of making claims. We therefore took evidence as to occurrence among miners from Dr. Moody on behalf of the Miners' Federation and from the Drs. W. Brown-Moir, T. Lester Llewellyn, W.E. Hume, and Robert McGhie on behalf of the Mining Association of Great Britain. Reference was made to the occurrence of the condition in railway servants, but the Amalgamated Society of Railway Servants felt unable to tender any evidence, and we therefore did not call on the Railway Companies, and, in the absence of occurrence in the shipbuilding trades, we eventually decided that the evidence tendered by the Federation of Shipbuilding Employees need not be taken."

"In view of Mr. Black's figures and having regard to the fact that no medical man in Nottingham spoke to the prevalence, we cannot say that a case of exceptional incidence among lace minders is conclusively made out, even in Nottingham, and therefore, we are of the opinion that Dupuytren's contraction in minders of lace machines ought not to be scheduled."

APPENDIX 2

Criteria Used to Assess Validity of Manual Work/ Vibrationa

Population

1. Was potential for bias in selection of subjects for study group or controls avoided?

Score: 3 Minimal or no flaws - all potential workers included; survivor bias (healthy worker effect) avoided

2 Minor flaws - volunteer bias possible; survivor bias possible (e.g. cross-sectional study design)

1 Major flaws - selection method not reported

2. Was nonrespondent bias avoided?

3 Minimal or no flaws - 90% or more responded

2 Minor flaws - response rate 75-89%; 90% or more in one group but not reported in other

1 Major flaws - response rate not reported; response rate < 75%

3. Were controls and study group comparable with respect to age, sex, socioeconomic status, ethnic origin, family history of Dupuytren's contracture, previous hand injury, and conditions associated with Dupuytren's contracture (such as diabetes, epilepsy, alcoholism/ cirrhosis)?

4 Minimal flaws - groups comparable on all the above; if not, items were controlled for in analysis

3 Minor flaws - age and gender measured, and controlled for in analysis, or 3 or more age strata

2 Significant flaws - age and sex measured but differences not properly controlled for in analysis (e.g. age restriction; only 2 strata; or those greater than 60 excluded)

1 Major flaws - personal confounders not reported or not measured

Exposure

4. Were the following confounding exposures controlled for in both control and study groups: other exposures at work or non-workplace stressors such as hobbies involving manual activities or vibration?

3 Minimal flaws - all relevant exposures measured and controlled for in analysis

2 Minor flaws - some or all confounders measured but differences not controlled for in analysis (e.g. may have asked about past jobs, other chemicals)

1 Major flaws - exposure confounders not reported or not measured (job title only)

5. Were direct and valid measures for exposure used such as years of manual labour, description of tools used, job titles used in ranking or classification, weights lifted or forces required, measures of repetition (frequency, duration of work cycle, number of work items)?

3 Minimal flaws - appropriate measures of exposure used: applied to controls and study group; measures of exposure applied to each individual subject/ control

2 Minor flaws - unable to measure exposure in controls with same method as study group but exposure highly unlikely (e.g. asked about tools used);

1 Major flaws - exposure measures not reported or not measured

Outcome

6. Were direct and valid criteria used to measure outcome?

3 Minimal flaws - relevant diagnostic entity (Dupuytren's contracture is only outcome of interest here); grading or staging system used is reported and referenced

2 Minor flaws - relevant diagnostic entity (Dupuytren's contracture is only outcome of interest); grading or staging system mentioned but grading or stages not given or referenced

1 Major flaws - outcome criteria not reported; no grading or staging system mentioned

7. Were the examiners of subjects' hands (in cross-sectional studies) blind to "exposure status" or were assessors of exposure (in case-control studies) blind to case-control status?

3 Minimal flaws - complete blinding of examiners/ assessors

1 Major flaws - blinding not done or not reported

a Adapted from Stock (1991)

APPENDIX 3

Articles Obtained and Considered That Did Not Meet Criteria

Case Series of Dupuytren's Contracture

Bell RC, Furness JA. A study of the effect of recurrent trauma on the development of Dupuytren's contracture. Br J Plast Surg 1977;30:149-150.

de Larrard J, Hitier CP, Dervilleé, Doignon J, Robert M. The role of traumatism in the etiology of Dupuytren's disease. Bordeaux 1969;721-724. [English translation]

Mackenney RP. A population study of Dupuytren's contracture. The Hand 1983;15:155-161.

Moorhead JJ. Trauma and Dupuytren's contracture. Am J Surg 1953;85:352-358.

Roberts FP. A vibration injury: Dupuytren's contracture. J Soc Occup Med 1981;31:148-150.

Yost J, Winters T, Fett HC. Dupuytren's contracture: a statistical study. Am J Surg 1955;90:568-571.

Zachariae L. Dupuytren's contracture: the aetiological role of trauma. Scand J Plast Reconstr Surg 1971;5:116-119.

Case Series of Dupuytren's Contracture Operated Upon

Marx J, Schunk W. On the role of occupational and dispositional factors in the origination of Dupuytren's contracture. Beitr Orthop u Traumatol 1982;29:477-483.

McFarlane RM, Botz JS, Cheung H. Epidemiology of surgical patients. In: McFarlane RM, McGrouther DA, Flint MH, editors. Dupuytren's disease: biology and treatment. New York: Churchill Livingstone, 1990a:201-238.

McFarlane RM, Shum DT. A single injury to the hand. In: McFarlane RM, McGrouther DA, Flint MH, editors. Dupuytren's disease: biology and treatment. New York: Churchill Livingstone, 1990:265-273.

Occupational Group without Comparison Groups

de la Caffinière JY, Wagner R, Etscheid J, Metzger F. Manual work and Dupuytren's disease: result of a computerized survey made among iron workers. Ann Chir Main 1983;2:66-72 (English translation). [No comparison of prevalence between groups given]

Pardi F, Ambrosino N, Bachini P, Loi AM, Paggiaro PL. Clinical and laboratory evaluation in vibration syndrome: a study on fifty subjects. G Ital Med Lav 1982;4:145-149. [English translation]

APPENDIX 4

Letter from Dr. Mikkelsen

APPENDIX

Bibliography of some original studies considered but excluded

Series of Dupuytren's contracture coming to surgery with control group

Marx J, Schunk W.

A series of DC cases operated on was compared to controls. Of 109 patients operated from 1969 to 1978, 62.4% appeared for follow-up and a control group of same age and sex but not further described. The patients were interviewed and examined. "Major stressing of the shoulder-arm-hand system for longer than 10 years was found in 22 (28.6%) of 77 cases and 7 (11.9%) of 59 controls (p<0.05); cases were exposed more frequently to "palmar stress" (41.6% vs 14%); and worked with vibration for at least 6 hrs/day for more than 1 year in 12 (15.6%) vs 3 (5.1%) but not significant. The authors concluded that the effects of heavy work and work with stresses of the palm "are to be rejected as factors in the origination or degeneration of Dupuytren's contracture" while "exposure to vibration is worthy of greater attention".

DETAILED RECOMMENDATIONS

1. To further address the association of DC with manual work, it may be possible to conduct better quality morbidity studies relatively rapidly. In particular, any studies should have examiners blinded to "exposure" status in cross-sectional studies. Details on the force and frequency of movements, number of work items completed per unit time, weight of tools, duration of work, and magnitude of vibration exposure if relevant, should be obtained. It may be reasonable to look at possible candidate "high" risk industries from which recent WCAT cases have arisen, such as the auto sector, with control subjects preferably drawn from the same industry.

2. With respect to the possible association of DC and vibration in particular, a source of highly exposed subjects may be found among those filing claims for VWF (regardless of whether they have VWF), or subjects in highly exposed jobs previously evaluated by Dr. Peter Pelmear ? check old papers; jobs; non-exposed subjects could be drawn from same companies.

3. With respect to the possible association of DC and single injury, one could design a prospective study, enrolling as "exposed" subjects, patients having hand injuries (fractures, lacerations, crush injuries (perhaps from hand/ plastic surgeon practice), and as "non-exposed" subjects, a sample of patients from these practices without injuries to the hand (i.e. with injuries to other body parts) could be followed for 2 or more years, for the development of DC. Again, examiners should be blinded to which group as far as possible.


APPENDIX B.

REVIEW OF "OCCUPATION AND DUPUYTREN'S CONTRACTURE" BY DR GARY LISS

Reviewed for the IDSP by
Susan R Stock MD MSc FRSC
April 1994

General comments

This review is an extremely thorough and rigorous one and the most complete review of this topic I have seen to date. It is apparent that much thought and work has gone into it. The approach taken is that of a systematic overview and it has included all the steps recommended for such an overview.

Completeness of literature search

Literature search methods were clearly spelled out Significant effort went into identifying as much of the relevant published literature as possible and the literature search appears quite comprehensive. It might have been useful to include a search of CIS, the ILO occupational health bibliographic database, as it includes a wide range of European studies that often are not included in Medline and contains unpublished PhD theses and public agency reports. Criteria for initial identification of relevant studies and for selection of studies to be included in the detailed review were stated. The criteria for the latter could have been more specific.

Primary question stated

A primary question for the systematic review of the epidemiologic literature was identified, ie "Is Dupuytren's contracture associated with manual work (possibly involving repetitive tasks and/or vibration; not involving a single injury')?

Validity study of the studies reviewed

The criteria questions used are appropriate and quite pertinent. The specific wording of the choices for scoring are somewhat ambiguous and could be improved. This likely would have improved the inter-rater reliability which was, at best, moderate. The decision to calculate odds ratios and confidence intervals for each of the studies was particularly useful for comparing strength of association or statistical significance.

Conclusions of the review

My interpretation of the results of this overview of manual work/vibration studies is somewhat different than the author's. Two of the studies rated 14/22, a moderate rating, and met at least the minimum standards for the criteria posing the greatest threat to validity. These studies are of moderately good quality and the only two upon which significant weight can be put. Both demonstrated a significant relationship between manual work or vibration and Dupuytren's contracture. It is only the much poorer studies which had negative conclusions. While these two studies certainly have methodologic weaknesses, and therefore their conclusions are not definitive, they do suggest a relationship between this disorder and biomechanical factors at work. The strong dose response relationships noted by Cocco for vibration is also very suggestive that a causal relationship may well exist. This relationship will need to be confirmed in better designed future studies as suggested in Dr Liss' recommendations.

Other comments

In order to sort out whether Dupuytren's contracture is associated with biomechanical factors at work, it is important to identify specific ergonomic factors that may contribute to the development of this disorder rather than speak of "manual work'' in a very vague and general sense.

It has been my understanding that one of the main mechanism hypothesized for the work-related development of this disorder is mechanical rubbing of tools or parts in the palm of the hand particularly when these tools or parts must be gripped very tightly. (Vibration, or the use of vibrating tools, is the other main mechanism hypothesized.)

This certainly has been my anecdotal experience. In 1988 I participated in the physical examination of some 200 meat processing workers in a huge US meat packing plant. We noted a high number of cases of Dupuytren's contracture and trigger finger in those who had to grip meat hooks to hold carcasses in place while they cut or otherwise manipulated them. These workers appeared to be exerting very high grip forces for most of their work day. This observation fits with Skoog's 1957 observation that the ulnar part of the aponeurosis is where the greatest strain occurs in grasping and passive support (Liss, p. 19) and with Hueston's 1987 observation that elderly women may develop Dupuytren's contracture after wearing a Colles' fracture cast (Liss, p. 25).

Future studies will need to test these hypotheses and ensure that exposures are measured in such a way that these factors are taken into account while controlling for relevant confounders and risk modifiers. ''Manual work's per se may not be relevant but rather work tasks that involve continuous and/or forceful grasping or gripping or exposure to vibrating tools.


CRITICAL ASSESSMENT OF THE REVIEW ABOUT WORK- AND INJURY-RELATEDNESS OF DUPUYTREN'S CONTRACTURE

Andreas Maetzel, MD
Ontario Workers' Compensation Institute -
Date: 6 April 1994

I) Introduction and methods

The purpose of this review is to critically assess Garry M. Liss's paper "Occupation and Dupuytren's Contracture" (referred to hereafter as the "paper").

In his paper Gary M Liss conducts a systematic review of the scientific literature on Dupuytren's Contracture (DC) with the goal of synthesizing evidence concerning two questions about the disease:

1) Is Dupuytren's Contracture (DC) associated with or caused by manual work particularly repetitive manual work (including vibration), and

2) Is DC associated with or caused by a single injury

To be useful, any review of scientific literature on a particular issue must involve a thorough compilation of the available literature, a narrowing down of that literature to that which is applicable, an assessment of the methodologies employed, and finally a synthesis of the findings. Reviews are an important source of information and for this reason much attention has been focussed on improving the scientific standards of reviews.

Criteria for assessing the quality of review articles have been published, [Oxman & Guyatt, 1988] and validated [Oxman et al., 1991], and I intend to apply the 11 criteria outlined by the McMaster group to evaluate the paper. The criteria have been designed to maximize reproducibility and ensure validity. They serve to discriminate among quality characteristics of reviews. They are as follows:

1) Were the search methods reported?

2) Were comprehensive search methods used to locate relevant studies?

3) Were explicit methods used to determine which articles to include in the review?

4) Was selection bias avoided?

5) Were validity criteria reported?

6) Was validity assessed appropriately?

7) Was the assessment of the primary studies reproducible and free from bias?

8) Were the methods used to combine studies reported?

9) Were the findings of the primary studies combined appropriately?

10) Were the conclusions supported by the reported data?

11) What was the overall scientific quality of the overview?

For each criterion the paper will be rated on the following seven-point scale:

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
where my rating will be represented by a grey shading of the respective value.

II) The organisation of the paper

The paper is divided into 8 parts. Parts 1 through 5 are narrative in nature and ,generally relate to pathogenic, diagnostic and epidemiological concepts regarding DC. Parts 6 through 8 focus- on the goals of the paper as these relate to the review of the evidence concerning the relationship between manual work/single injury and DC.

III) Application of the McMaster Criteria

1) Were the search methods reported?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
Explicit specifications of exposure, outcome and populations are essential and have to be incorporated into the search methods. Using the keywords occupation, Dupuytren's Contracture, cumulative trauma, and acute injury the author has done a good job incorporating exposure and outcome into his search methods. A more comprehensive search incorporating text- and/or keywords like work, agricultural worker's diseases, injury, trauma could have been used to broaden the search, since the author points out the confusion about these terms on page 13. However, it is questionable if a broader search had yielded more articles due to the paucity of the published research on this topic.

2) Were comprehensive search methods used to locate relevant studies?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
The author has undertaken a very comprehensive literature search by consulting MEDLINE as well as NIOSHTIC databases, by reviewing occupational medicine texts and books on Dupuytren's contracture, and by examining the references provided in the studies. Index Medicus has been searched by hand for the years 1990 through 1993. This demonstrates the author's awareness of the limitations of electronic literature searches and guarantees sufficient comprehensiveness of the literature search. Some might suggest that an effort be made to search unpublished literature. However this is very difficult to do and its value is debated in the scientific community.

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
3) Were explicit methods used to determine which articles to include in the review?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
While the author makes every effort to select studies that employ specific and detailed exposure measurements, he also acknowledges the limitations of being overly explicit. Occupational exposure is often only broadly defined. For example, occupational exposure will usually be measured as a function of job title rather than with a detailed reference to specific body movements and actions. Even large and well-designed studies like the Framingham Study or the National Health and Nutrition Examination Survey (NHANES) limit the definition of occupational exposure to job title. Upon reviewing the available evidence one is unfortunately restricted to such simple exposure definitions which in fact limit the conclusions that can be drawn from the available research.

Although it might be suspected that a disease like DC might be better defined for epidemiologic studies, the author demonstrated the inconsistency in currently available disease classifications. Therefore I conclude that the author used inclusion criteria which were well suited to the existing knowledge.

4) Was selection bias avoided?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
The author specified how primary articles were chosen. The author however did not test whether the inclusion criteria yielded reliable results. He could have done this in the same way he assessed validity by choosing a second examiner applying the inclusion criteria without knowledge of the authors results. Had this approach been used, a statistical measure of agreement could have been reported. This procedure would have added additional credibility to the work, by serving as a check against bias.

5) Were validity criteria reported?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
This part of the review is very crucial since it relates to the validity of the findings and the generalizability of the results. The author uses criteria developed by Susan Stock in her review on workplace ergonomic factors and the development of musculoskeletal disorders of the neck and upper limbs. The validity criteria used by the author satisfy fundamental requirements concerning the judgment of epidemiological studies. They are supported by modern textbooks [Rothman, 1987] and also other authors who synthesized evidence from nonexperimental studies [Esdaile and Horwitz, 1986; Stock, 1991]. In particular the following characteristics are required (and were present in the paper):

a) Avoidance of selection bias

b) Unbiased exposure ascertainment

c) Unbiased outcome ascertainment

d) Control for obvious confounders

e) Adequate follow-up of all those enrolled or satisfactory participation by cases and controls

6)Was validity assessed appropriately?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
" Authors will come to correct conclusions only if they accurately assess the validity of the primary studies on which the review is based. If all the studies have basic flaws their conclusions may be questionable even if their results are comparable [Oxman & Guyatt, 1988]".

It is obvious that a study with major flaws in all of the mentioned qhality _characteristics cannot be considered as having valid results. It is nevertheless a matter of choice where to put the threshold for non-consideration. Susan Stock for example in her article [Stock, 1991] concludes that "Prior to assessment it was decided that, if any study had major flaws, (i.e., score of 1 on the validity assessment tool) in any of these areas (comparability of the groups and validity of exposure and outcome measures), the validity of the results of that study would be seriously compromised, and the study would not be included in any aggregate analysis" [Stock, 1991 p.91]. When considering whether to exclude any study with a major flaw in one or more of the criteria, one ought to do so if it can be proven that this or these flaws seriously compromise the conclusion. The author conducted a very thorough assessment and has done a good job, given the quality of the studies he had to work with.

7) Was the assessment of the primary studies reproducible and free from bias?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
"Ideally the potential primary studies should be assessed for inclusion by at least two authors, each blind to the other's decision, and the extent of agreement should be recorded. Reproducibility should be quantified with a statistical measure that quantitates agreement ... such as an intraclass correlation coefficient or a kappa statistic" [Oxman & Guyatt, 1988].

The author follows high quality standards to ensure reproducibility of the assessments. This is demonstrated by the high agreement among the two observers. However, validity assessments are lacking for the three "non-english" studies; therefore it is difficult to say that the assessment was free from bias and it would have been desirable to see also the results for those three studies.

8) Were the methods used to combine studies reported?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
In order to combine results from epidemiologic studies several conditions must be met. Exposure categories must be identically defined for the results to be combined across studies. Otherwise, without a common definition, the combined measure will have no real meaning. Although there are methods to adjust odd's ratios coming from studies with different exposure measurements, these adjustments only can take place if the correction factor is known from previous studies. Clearly the paucity of available studies makes any adjustment of odd's ratios impossible. The author correctly avoided combining the results of the studies because of the major differences in study design, and exposure and disease classification.

9) Were the findings of the primary studies combined appropriately?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
As mentioned above, it was not appropriate to combine the results of the studies.

Although it does not fall under the McMaster criteria it is worth noting that the author is the only person to extract the results and calculate odd's ratios from the raw data provided in the literature. This step of data-extraction is very prone to error and I strongly recommend that data extraction and calculation be performed by a second examiner and that each examiner possibly do this procedure twice.

10) Were the conclusions supported by the reported data?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
Because the results can't be statistically combined the author should state explicitly the basis for his conclusions.

In his conclusion the author discusses all studies included in the review. However, as the author points out, from table 7 it is obvious that 4 of the 6 studies lack even basic quality standards to merit further consideration. Strictly speaking, these studies should be excluded from the analysis.

The characteristics of the remaining studies are only briefly discussed. In my view, this discussion should have been more explicit. For example, how large is the influence of existing bias for the reported results? Do the biases lead to over- or underestimation of the odd's ratios?

For example, the study by Bennet may suffer from selection bias since it used different populations for index- and comparison-group, whereas the study by Thomas & Clarke does not. Even though the bottomline of both studies shows that there is a positive association.

Both lacked blinding of the examiners for outcome ascertainment. This is a problem if DC is defined by the presence of nodules. DC was defined this way in both studies whereas it was defined as presence of contracture in the study by Cocco. The effect of unblinded observers probably will be negligible in this latter study.

All studies, even those of good quality lacked blinding to case status during determination of exposure. This is a considerable problem if determination of exposure is susceptible to recall-bias but is probably less relevant if exposure is restricted to job title.

Confounding factors which are associated both with exposure as well as disease have been considered in the validity assessment. The assessed studies did adjust for age and gender and it is debatable whether adjustment for the other confounders mentioned in the validity criteria would have had a big impact on the final result, e.g., ethnic origin won't be of relevance in the study by Bennet and it is debatable whether measurement and adjustment for family history of DC would have yielded more precise results, since measurement of family history as such is prone to error.

In my opinion the biases of the better rated studies probably would have led to overestimation. How much is difficult to say since a high standard study is unavailable. The author considers the guidelines for assessing the strength of a causal inference:

1)Is the temporal relation correct?

2)Is the evidence strong?

3)Is the association strong?

4)Is there consistency between studies?

5) Is there a dose-response relation?

6) Is there indirect evidence that supports the inference?

7) Have the plausible competing hypotheses been ruled out?

The author correctly concludes that there is insufficient evidence to definitely say that DC is a disease related to manual work. The results nevertheless strongly suggest a possible association although this remains to be confirmed by future studies.

What was the overall scientific quality of the overview?

          1          2          3          4          5          6          7
   Extensive Flaws         Major Flaws            Minor Flaws        Minimal Flaws
    (Very Poor)               (Poor)                (Good)            (Exemplary)
The author selected the relevant research and thoroughly presented the validity of the research that was reviewed.

In the initial sections of his work the author describes the disease, and discusses epidemiological characteristics and pathogenetic concepts.

These sections, in my mind, provide relevant information to the reader who needs to be informed about the disease, its epidemiology and the common pitfalls when studying a disease with a probable multifactorial etiology. The author correctly points out the numerous difficulties encountered in the study of DC, e.g., the absence of diagnostic criteria, the presence of disorders which mimic DC, and the difficulties in establishing a hereditary disease pattern. These sections of the paper however do not contribute to the analysis of the special question he wants to address.

The discussion about single injury and DC reported in section 7, if considered under the same rigorous criteria as the review of the evidence about the relatedness of DC to manual work, is rather narrative. There seems to be no scientific evidence with which to make a valid conclusion. The discussions in different textbooks are narrative in nature and dominated by beliefs and opinions. The diverging opinions among experts are also reflected in the information presented in the table on page 17. Therefore the guidelines forwarded by McFarlane and Shum should be welcomed but certainly would be improved if consensus existed among experts, otherwise they will stay as arbitrary as they appear. A more thorough data-extraction also would have added to the quality of the paper. Finally, the references Thomas & Clarke, and Herzog should be added to the reference section of the paper.

IV) Commentary

I found the paper useful as a review of DC's relatedness to work. In this regard I believe that the author thoroughly assembled and analysed the available literature according to the issues addressed. The scientific methods were properly employed.

My only criticism of the paper relates to its organization. In my view the lead-in to the paper's main purpose is inordinately lengthy. The paper really only sets out to fulfill its goals in chapter 6 through 8 and the tables in the appendix, which are very useful.

V) References

1. Esdaile JM, Horwitz RI. Observational studies of cause effect relationships: an analysis of methodologic problems as illustrated by the conflicting data for the role of oral contraceptives in the etiology of rheumatoid arthritis. Journal of Chronic Diseases. 1986;39:841-852.

2. Oxman AD, Guyatt GH, Singer J et al. Agreement among reviewers of review articles. J Clin Epidemiol. 1991;44:91-98.

3. Oxman AD, Guyatt GH. Guidelines for reading literature reviews. CMAJ. 1988;138(83:697-703.

4. Rothman KJ. Modern Epidemiology. Boston/Toronto: Little,Brown and Company; 1986.

5. Stock SR Workplace ergonomic factors and the development of musculoskeletal disorders of the neck and upper limbs: a meta-analysis. Am J Ind Med. 1991;19:87-107.


APPENDIX C.
GLOSSARY OF SOME EPIDEMIOLOGICAL TERMS

case-control study: A study that identifies people with a condition (usually a disease or cause of death), who are called cases, and people without that condition, who are called controls, then compares the frequency and/or severity of their exposure(s) that occurred before the condition developed. Case-control studies usually examine the incidence of a certain type of cancer, for example, rather than deaths caused by that cancer type. A nested case-control study is one in which the subjects are drawn from a cohort study and comparisons made between the exposures of cases and controls.

cohort study: A study that starts with a group of people who have something in common (such as a workplace or occupation), who are called a cohort. It identifies the frequency and/or severity of their exposure(s), follows them to see what disease(s) occur, then compares them to a control group that did not have the exposure(s).

95% confidence interval: See SMR, below.

confounders: Factors that can influence the results of studies (e.g. smoking) other than the factor under study (which is, in this case, the effect of metalworking fluid exposure).

to control for: To take into account, in the design of a study or in the analysis of its results, factors other than those being studied which could have influenced the results (confounders).

dose-response: A dose-response trend is shown when an increase in the "dose" (exposure level, intensity or duration) corresponds to an increase in the "response" (death or disease rate). Since detailed occupational exposure data is rarely available, most authors measure "dose" by the duration of exposed employment.

epidemiology: The study of disease patterns in groups of people.

goodness of fit: In general, this refers to the agreement between predictions from a statistical model and the data that were actually observed. If the differences between the observed data and the predicted data are no larger than would be expected by random variation, then the model is said to be a good fit and is considered to be a good representation of the data. If these differences are much larger than random variation would suggest, then the model is not a good fit.

healthy worker effect: Many epidemiological studies compare workers with the general population. Since the general population includes people who do not or cannot work due to illness or disability, a working population is usually healthier and is expected to have a lower mortality rate for most causes of death. The influence of these factors on the results of studies is known as the "healthy worker effect". It results in lower SMRs than would occur if more similar groups had been compared and may conceal a real increase in deaths among workers. Comparisons with another group of "healthy" workers, rather than to the general population, are therefore more likely to provide accurate statistical estimates of occupational risks.

Whether or not the healthy worker effect influences cancer mortality ratios is controversial. In a previous Report [Number 3; July, 1988], the Panel published comments on the healthy worker effect solicited from nine experts. The Panel's review of those opinions led it to conclude that the healthy worker effect must be taken into account when interpreting epidemiological studies of mortality or morbidity from any cause, including cancer. No uniform correction factor should be used because each study requires individual interpretation.

lagging: If a period of X years must elapse between exposure to a carcinogen and potential development of cancer, then exposures in the X years prior to a given time may not increase the risk at that given time. If these years were included in the calculation of exposure, a true dose-response trend may be obscured. To account for this, many studies lag exposures by X years. This means that in calculating exposure, any exposures in the X years before a given time are excluded. In other words, exposures do not count until X years after they occur.

latency period: The period of time between the first exposure to a substance(s) and the appearance of the disease which the exposure(s) has caused. Latency is usually measured by the time since the first exposed employment.

Likelihood Ratio Statistic (LRS): The LRS (literally, the ratio of how likely one model is to how likely another is) is used to decide between competing statistical models for a given set of data. If one model includes a set of variables X and another model includes the set X+Z, the likelihood ratio statistic is used to determine whether Z should be included in the model. Only if the model with X+Z is much more likely than the model with X alone should Z be included. Often, the LRS is given for the comparison of a given model to the null model (this being a single, one-number summary of the entire data set), and is a test of overall significance of all the variables included in the model.

odds ratio (OR): Case-control studies, as opposed to cohort studies, report their results in terms of an odds ratio. This represents the likelihood that observed cases had a certain exposure, compared to the likelihood that controls had that exposure. An equal likelihood is expressed as 1.

power: The probability that a risk of a certain size will give a significant result. For example, a study might have 80% power to detect a relative risk of 1.4. If a study does not identify a significant result, but does not have sufficient statistical power (sufficient numbers of cases) to identify a significant result, it is uninformative. A study could have limited power and still identify a significant increase in risk.

Here is a graphic description of the generally accepted principles used by the Panel:
SIGNIFICANT RESULT NON-SIGNIFICANT RESULT
HIGH POWER conclusive positive result conclusive negative result
LOW POWER conclusive positive result inconclusive

proportional mortality ratio (PMR): The PMR is the proportion of the group being studied that have died of a certain cause compared to the proportion expected to die of that cause in the general population. The cases are usually the same age, sex, race and year of death as the members of the general (comparison) population. A PMR of more than 100 suggests an excess risk, similar to an SMR, as discussed below.

proportional cancer mortality ratio (PCMR): The PCMR is the proportion of the group being studied that have died of a certain type of cancer compared to the proportion expected to die of that cancer in the general population. The cases are usually the same age, sex, race and year of death as the members of the general (comparison) population. A PCMR of more than 100 suggests an excess risk, similar to an SMR, as discussed below.

relative risk (RR): An estimate of how much more common a certain disease (or cause of death) is in a study group than in a comparison population. Also known as the "rate ratio", it is the rate of the exposed group divided by the rate of the comparison group. An approximation of the RR is the Odds Ratio from a case-control study.

retrospective cohort study: A study which looks back in time at a group of people to determine whether an occupationally exposed group has a different pattern of mortality or disease from a non-exposed group.

standardized mortality ratio (SMR): An SMR is calculated by comparing the number of deaths observed (that is, deaths that occurred) among the people being studied with the number of deaths that are expected based upon a comparison group of the same age and sex, during the same time period:

                            "observed" deaths            }
SMR  =  -------------------------------------------------} (x 100)
                            "expected" deaths            }

Most authors multiply the ratio by 100 to avoid using fractions, but some do not; so, an SMR of 1.98 is the same as an SMR of 198. 100 is the expected, or "normal". An SMR greater than 100 (or 1) suggests an excess risk of death or disease. Epidemiologists evaluate the statistical significance of an elevated SMR by using the 95% confidence interval, which is the range in which the true SMR would fall in 95% of cases. (In this Report, the 95% confidence interval is shown in brackets, following the SMR; "n" refers to the number of cases or deaths.)

If the lower end of the 95% confidence interval is above 100 (or 1), the likelihood that the excess of deaths or disease is caused by chance is less than 5% (or 1 out of 20). If the SMR is under 100 (or 1) and the upper end of the 95% confidence interval is also under 100 (or 1), a statistically significant decrease in deaths or disease is indicated, compared to the number of deaths that would normally be expected.

statistically significant: See SMR, above.


October 3, 1996

Mr. Glen Wright
Chairman
Workers' Compensation Board
200 Front Street West, 18th floor
Toronto, Ontario
M5V 3J1

Dear Mr. Wright:

I enclose a copy of the Panel's Report to the Workers' Compensation Board on Dupuytren's Contracture and Hand Injury.

I would be pleased to discuss the Report with you. Please let me know when it would be convenient to do so.

Sincerely,


Nicolette Carlan
Chair

Enclosure


Endnotes

1. In this Report, the term, disease, means disease or condition or both.

2. Saskatchewan, Manitoba and PEI compensate accidents and occupational diseases case-by-case. Manitoba has no schedule but includes diseases in the definition of accident and has a separate definition of occupational disease. The Manitoba WCB uses guidelines for diseases.

3. DC in the penis is called Peyronie's Disease.

4. Collagen is a major type of fibrous protein found in tendons, bone, skin, cartilage and elsewhere. Its structure is based on three helical polypeptide chains wound together to form rod-like molecules. Twelve genetically distinct types of collagen have been identified based on the underlying amino acid sequence and composition that determines its shape and function.

5. The majority of authors used duration of employment using vibratory tools as the exposure standard. Bovenzi was the only author to specifically quantify vibration exposure. In his study "vibration was measured on a representative sample of percussive and rotary tools. The 8h energy equivalent and lifetime vibration doses were calculated for each of the exposed stone workers."

6. VWF = vibration white finger disease.

7. There are no statistics on double hand injury and early onset of DC; however, the implication is that any hand injury can be related to DC at an early age.

8. This theory remains untested by comparison to cases of unilateral early onset without hand injury. cf. Liss review.

9. Presumably, this threshold age is chosen because 50% of expected cases occur between 40 and 60 in males, and between 50 and 70 in females (Appendix 1).

10. Alcoholism, epilepsy, diabetes would therefore rule out any other accelerating factor.