Pathogenesis of Foot Ulcers and the Need for Offloading

Abstract

Diabetic foot ulceration represents a major medical, social and economic problem all over the world. While more than 5 % of diabetic patients have a history of foot ulceration, the cumulative lifetime incidence may be as high as 15 %. Ethnic differences exist in both ulcer and amputation incidences. Foot ulceration results from the interaction of several contributory factors, the most important of which is neuropathy. The use of the total-contact cast is demonstrated in the treatment of plantar neuropathic ulcers. Histological evidence suggests that pressure relief results in chronic foot ulcers changing their morphological appearance by displaying some features of an acute wound. Thus, repetitive stresses on the insensate foot appear to play a major role in maintaining ulcer chronicity. It is hoped that research activity in foot disease will ultimately result in fewer ulcers and less amputation in diabetes.

Key words

Diabetic foot - Diabetic neuropathy - Foot ulcer - Amputation - Total Contact Cast (TCC)

References

• 1 Wild S, Roglie G, Green A, King H. Global prevalence of diabetes: estimates for 2000 and projections for 2030.  Diabetes Care;. 2004;  27 1047-1053
• 2 Boyko E J, Ahroni J H, Smith D G, Davignon D. Increased mortality associated with diabetic foot ulcer.  Diabetic Med. 1996;  13 967-972
• 3 Krentz A J, Acheson P, Basu A, Kilvert A, Wright A D, Natrass M. Morbidity and mortality associated with diabetic foot disease: a 12-month prospective survey of hospital admissions in a single UK centre.  Foot. 1997;  7 144-147
• 4 Jude E B, Boulton A JM. End stage complications of diabetic neuropathy.  Diabetes Reviews. 1999;  7 395-410
• 5 Shaw J E, Zimmet P Z. The epidemiology of diabetic neuropathy.  Diabetes Rev. 1999;  6 245-252
• 6 Williams D RR, Airey M. The size of the problem: epidemiological and economical aspects of the diabetic foot. In: Boulton AJM, Connor H, Cavanagh PR (eds) The foot in diabetes; 3rd edition. Chichester; Wiley 2000: 3-17
• 7 Reiber G E, Ledoux W R. Epidemiology of diabetic foot ulcers and amputations: evidence for prevention. In: Williams R, Herman W, Kinmonth AL, Wareham NJ (eds) The evidence base for diabetes care. Chichester; Wiley 2002: 641-665
• 8 Carrington A L, Abbott C A, Griffiths J, Jackson N, van Ross E RE, Boulton A JM. A foot care programme for diabetic unilateral amputees.  Diabetes Care. 2001;  24 216-221
• 9 Kumar S, Ashe H, Fernando D JS, Tsigos C, Young R J, Boulton A JM. The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population-based study.  Diabetic Med. 1994;  11 480-484
• 10 Abbott C A, Carrington A L, Ashe H. et al . The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort.  Diabetic Med. 2002;  20 377-384
• 11 Muller I S, de Graum W J, van Gerwen W H. et al . Foot ulceration and lower limb amputation in type 2 diabetic patients in Dutch primary health care.  Diabetes Care. 2002;  25 570-574
• 12 Lavery L A, Armstrong D G, Wunderlich R P, Tredwell J, Boulton A JM. Diabetic Foot Syndrome: evaluating the prevalence and incidence of foot pathology in Mexican Americans and non-hispanic whites from a diabetes management cohort.  Diabetes Care. 2003;  26 1435-1438
• 13 Humphrey A RG, Thomas K, Dowse G K, Zimmet P Z. Diabetes and non-traumatic lower extremity amputations. Incidence, risk factors and prevention: a 12 year follow-up study in Nauru.  Diabetes Care. 1996;  19 710-714
• 14 Behhadj M A. La pace du pied diabetique [in French].  Diabete Metab. 1998;  24 [Supp] LXVII
• 15 Pendsey S. Epidemiological aspects of the diabetic foot.  J Diabetes Develop Countries. 1998;  2 37-38
• 16 Young M A, Veves A, Breddy J L, Boulton A JM. The prediction of diabetic neuropathic foot ulceration using vibration perception thresholds: a prospective study.  Diabetes Care. 1994;  17 557-560
• 17 Abbott C A, Vileikyte L, Williamson S, Carrington A L, Boulton A JM. Multicentre study of the incidence of and predictive factors for diabetic neuropathic foot ulcers.  Diabetes Care. 1998;  21 1071-1075
• 18 Larsson J, Apelqvist J, Agardh G D, Stenstrom A. Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach?.  Diabetic Med. 1995;  12 770-776
• 19 Trautner C, Haastert B, Spraul M, Giani C, Berger M. Unchanged incidence of lower limb amputations in a German city 1990 - 1998.  Diabetes Care. 2001;  24 855-859
• 20 Trautner C, Haastert B, Giani C, Berger M. Amputations and diabetes: a case control study.  Diabetic Med. 2002;  19 35-40
• 21 No authors listed. An audit of amputations in a rural health district.  Practical Diabetes Int. 1997;  14 174-178
• 22 Toledano H, Young M J, Veves A, Boulton A JM. Why do Asian diabetic patients have fewer foot ulcers than Caucasians.  Diabetic Med. 1993;  [Suppl 1] 539
• 23 Chaturvedi N, Abbot C A, Whalley A, Leggetter S Y, Boulton A JM. Risk of diabetes-related amputation in south Asians vs. Europeans in the UK.  Diabetic Med. 2002;  10 19 99-106
• 24 Leggetter S Y, Chaturvedi N, Fuller J H, Edmonds M E. Ethnicity and risk of diabetes-related lower extremity amputation: a population-based, case-control study of Afro-Caribbeans and Europeans in the United Kingdom.  Arch Int Med. 2001;  162 73-78
• 25 Resnick H E, Valsania P, Phillips C L. Diabetes mellitus and non-traumatic lower extremity in black and white Americans: the national health and nutrition examination survey epidemiology follow-up study 1971 - 1992.  Arch Int Med. 1999;  159 2470-2475
• 26 Most R S, Sinnock P. The epidemiology of lower extremity amputations in diabetic individuals.  Diabetes Care. 1983;  6 87-91
• 27 American Diabetes Association . Consensus development conference on diabetic wound care.  Diabetes Care. 1999;  22 1354-1360
• 28 Shearer A, Schuffham P, Gordois A, Ogleshy A. Predicted costs and outcomes from reduced vibration detection in people with diabetes in the US.  Diabetes Care. 2003;  26 2305-2310
• 29 Ragnarson-Tennvall G, Apelqvist J. Prevention of diabetes-related foot ulcers and amputations: a cost utility analysis based on Markov model simulation.  Diabetologia. 2001;  44 2077-2087
• 30 Assal J P, Mehnert H, Tritschler H S, Sidorenko A, Keen H. ‘On your feet’ workshop on the diabetic foot.  J Diabet Comp. 2002;  16 183-194
• 31 Ramsey S D, Newton K, Blough D. et al . Incidence outcomes and costs of foot ulcers in patients with diabetes.  Diabetes Care. 1999;  22 382-387
• 32 Diabetes care and research in Europe: the St Vincent Declaration. Diabet Med 1990 7: 360
• 33 Larssen J. Lower extremity amputations in diabetic patients. Doctoral thesis. Lund University 1994
• 34 Boulton A JM. The pathway to ulceration: aetiopathogenesis. In: Boulton AJM, Connor H, Cavanagh HPR (eds) The foot in diabetes, 3rd edition. Chichester; Wiley 2000: 19-31
• 35 Reiber G E, Vileikyte L, Boyko E J. et al . Causal pathway for incident lower extremity ulcers in patients with diabetes from two settings.  Diabetes Care. 1999;  22 157-162
• 36 Boulton A JM, Hardisty C A, Betts R P. et al . Dynamic foot pressure and other studies as diagnostic and management aids for diabetic neuropathy.  Diabetes Care. 1983;  6 26-33
• 37 Katoulis E C, Ebdon-Parry M, Hollis S. et al . Postural instability in diabetic patients at risk of foot ulceration.  Diabetic Med. 1997;  14 296-300
• 38 Katoulis E C, Ebdon-Parry M, Lanshammer H. et al . Gait abnormalities in diabetic neuropathy.  Diabetes Care. 1997;  20 1904-1907
• 39 Vileikyte L, Rubin R R, Leventhal H. Psychological aspects of diabetic neuropathy and its late sequelae.  Diab Metab Res Rev. 2004;  20 [Suppl 1] S13-S18
• 40 Young M J, Boulton A JM, MacLeod A F, Williams D RR, Sonksen P H. A multicentre study of the prevalence of diabetic peripheral neuropathy in the UK hospital clinic population.  Diabetologia. 1993;  36 150-154
• 41 Mayfield J A, Sugarman J R. The use of the Semmes-Weinstein monofilament and other threshold tests for preventing foot ulcerations and amputations in persons with diabetes.  J Fam Pract. 2000;  49 [Suppl 11] S17-S29
• 42 Booth J, Young M J. Differences in the performance of commercially available monofilaments.  Diabetes Care. 2000;  23 984-988
• 43 Miranda-Palma B, Basu S, Mizel M S. et al . The monofilament as gold standard for foot ulcer risk screening: a reappraisal.  Diabetes. 2003;  53 [Suppl 1] A63
• 44 Carrington A L, Shaw J E, Van Schie C HM, Abbott C A, Vileikyte L, Boulton A JM. Can motor nerve conduction velocity predict foot problems in diabetes over a six year outcome period?.  Diabetes Care. 2002;  25 2010-2015
• 45 National Diabetes Advisory Board .The prevention and treatment of five complications of diabetes: a guide for primary care practitioners. Atlanta, GA; Centers for Disease Control HHS publ. no. 83-8392 1983
• 46 Jude E B, Oyibo S O, Chalmers N, Boulton A JM. Peripheral arterial disease in diabetic and non-diabetic patients: a comparison of severity and outcome.  Diabetes Care. 2001;  24 1433-1437
• 47 Lavery L A, Armstrong D G, Vela S A. et al . Practical criteria for screening patients at high risk of diabetic foot ulceration.  Arch Int Med. 1998;  26 157-162
• 48 Murray H J, Young M J, Boulton A JM. The relationship between callus formation, high pressures and neuropathy in diabetic foot ulceration.  Diabetic Med. 1996;  13 979-982
• 49 Valk G D, Kreigsman D M, Assendelf W J. Patient education for reducing diabetic foot ulceration: a systematic review.  Endocrinol Metab Clin N Amer. 2002;  31 633-658
• 50 McCabe C J, Stevenson R C, Dolan A M. Evaluation of a diabetic foot screening and prevention programme.  Diabetic Med. 1998;  15 80-84
• 51 Vileikyte L. Psychological and behavioural issues in diabetic neuropathic foot ulceration. In: Boulton AJM, Connor H, Cavanagh PR (eds) The foot in diabetes, 3rd edition. Chichester; Wiley 2000: 121-130
• 52 Veves A, Boulton A JM. The optical pedobarograph.  Clin Podiatr Med Surg. 1993;  10 463-470
• 53 Boulton A JM, Betts R P, Franks C I. et al . Abnormalities of foot pressure in early diabetic neuropathy.  Diabetic Med. 1987;  4 225-228
• 54 Boulton A JM, Betts R P, Franks C I, Ward J D, Duckworth T. The natural history of foot pressure abnormalities in neuropathic diabetic subjects.  Diabetes Res. 1987;  5 73-77
• 55 Newrick P G, Cochrane T, Betts R P, Ward J D, Boulton A JM. Reduced hyperaemic response under the neuropathic diabetic foot.  Diabetic Med. 1988;  5 570-573
• 56 Young M J, Cavanagh P R, Thomas G. et al . The effect of callus removal on dynamic plantar foot pressures in diabetic patients.  Diabetic Med. 1992;  9 55-57
• 57 Veves A, Young M J, Murray H J, Boulton A JM. The risk of foot ulceration in diabetic patients with high foot pressures: a prospective study.  Diabetologia. 1993;  35 660-663
• 58 Lavery L A, Armstrong D G, Wunderlich R P, R T redwell, Boulton A JM. Predictive value of foot pressure assessment when part of a population based diabetes disease management programme.  Diabetes Care. 2003;  26 1069-1073
• 59 Jeffcoate W J, Harding K G. Diabetic foot ulcers.  Lancet. 2003;  361 1545-1551
• 60 Jude E B, Blakytny R, Bulmer J, Boulton A JM, Ferguson M WJ. Transforming growth factor-beta 1, 2, 3 and receptor type 1 and 2 in diabetic foot ulcers.  Diabetic Med. 2002;  19 440-447
• 61 Lobmann R, Ambrosch A, Schultz G. et al . Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients.  Diabetologia. 2002;  45 1011-1016
• 62 Boulton A JM, Armstrong D G. Studies in planter diabetic neuropathic ulcers; time for a paradigm shift?.  Diabetes Care. 2003;  26 2689-2690
• 63 Brand P W. The Diabetic Foot. In: Ellenberg M, Rifkin H (eds) Diabetes mellitus: theory and practice, 3rd edn. New York; Med Exam Publishing 1983: 829-849
• 64 Boulton A JM. Lawrence Lecture: the diabetic foot: neuropathic in aetiology?.  Diabetic Med. 1990;  7 852-858
• 65 Armstrong D G, Nguyen H C, Lavery L A, van Schie C H, Boulton A JM, Harkless L BI. Off-Loading the diabetic foot wound: a randomized clinical trial.  Diabetes Care. 2001;  24 1019-1022
• 66 Armstrong D G, Stacpoole-Shea S. TCC and removable cast walker. Mitigation of plantar heel pressure.  J Am Podiatr Med Assoc. 1999;  89 50-53
• 67 Boulton A JM, Bowker J H, Gadia M. et al . Use of plaster casts in the management of diabetic neuropathic foot ulcers.  Diabetes Care. 1986;  9 149-152
• 68 Mueller M J, Diamond J E, Sinacore D R. et al . Total contact casting in the treatment of diabetic plantar ulcers: controlled clinical trial.  Diabetes Care. 1989;  12 384-388
• 69 Mason J, O’Keefe C, Hutchinson A, McIntosh A, Young R, Booth A. A systematic review of foot ulcers in patients with type 2 diabetes mellitus treatment.  Diabetic Med. 1999;  16 889-909
• 70 Lavery L A, Vela S A, Lavery D C, Quebedeaux T L. Reducing dynamic foot pressures in high-risk diabetic subjects with foot ulcerations: a comparison of treatments.  Diabetes Care. 1996;  19 818-821
• 71 Baumhauer J F, Wervery R, McWilliams J, Harris G F, Shereff M J. A comparison study of plantar foot pressure in a standardized shoe, total contact cast prefabricated pneumatic walking brace.  Foot Ankle Int. 1997;  18 26-33
• 72 Armstrong D G, Lavery L A, Kimbriel H R, Nixon B P, Boulton A JM. Activity patterns of patients with diabetic foot ulceration: patients with active ulceration may not adhere to pressure offloading regimen.  Diabetes Care. 2003;  26 2595-2597
• 73 Veves A, Sheehan P, Pham H T. A randomized control trial of Promogran vs standard treatment in the management of diabetic foot ulcers.  Arch Surg. 2002;  137 822-827
• 74 Ha Van G, Siney H, Hartmann-Heurtier A, Jacqueminet S, Greau F, Grimaldi A. Nonremovable, windowed, fibreglass cast boot in the treatment of diabetic planter ulcers: efficacy, safety and compliance.  Diabetes Care. 2003;  26 2848-2852
• 75 Spencer S. Pressure relieving interventions for preventing and treating diabetic foot ulcers (Cochrane Review).  In: The Cochrane Library. Issue 3. Chichester; John Wiley and Sons Ltd 2002
• 76 Armstrong D G, Short B, Espensen E H, Abu-Ramman P L, Nixon B P, Boulton A JM. Technique for fabrication of an ‘instant total contact cast’ for treatment of neuropathic diabetic foot ulcers.  J Am Pod Med Assoc. 2002;  92 405-408
• 77 Katz I, Harlan A, Miranda-Palma B. et al . A randomised trial of two irremovable offloading devices in the management of plantar neuropathic diabetic foot ulcers.  Diabetes Care. 2005;  28 555-559
• 78 Piaggesi A, Viacava P, Rizzo L. et al . Semi-quantitative analysis of the histopathological features of the neuropathic foot ulcer-effects of pressure relief.  Diabetes Care. 2003;  26 3123-3128
• 79 Knowles E A, Armstrong D G, Hayat S A, Boulton A JM. et al . Offloading diabetic foot wounds using the scotchcast boot: a retrospective study.  Ostomy Wound Manage. 2002;  48 50-53
• 80 Armstrong D G, Lavery L A, Wu S, Boulton A J. Evaluation of removable and irremovable cast walkers in the healing of diabetic foot wounds: a randomized controlled trial.  Diabetes Care. 2005;  28 551-554