Archive \ Volume.11 2020 Issue 3

Assessment of Diabetic Foot Ulcer Prognosis and Management

 

Ahmed Ghareeb Ghareeb1*, Mohammed Abdullah Alqahtani2, Khalid Hassan Asiri2, Abdulrhman Abubaker Alamoodi3, Lama Balkhair4, Muteb Naif Al Quwayd4, Ayman Adel Alsam4, Abdullah Khalid Alferaih4, Abdulaziz Saleh Alluhaydan4, Abdullah Fahad Khalil Alfahal5, Meshael alawi Almatari6

 

 

1 Department of General Surgery, Procore Hospital, Al Khobar, KSA. 2 Faculty of Medicine, King Khalid University, Abha, KSA. 3 Faculty of Medicine, Ibn Sina National College for Medical Studies, Jeddah, KSA. 4 Faculty of Medicine, Dar Aluloom University, Riyadh, KSA. 5 Faculty of Medicine, King Abdulaziz University, Jeddah, KSA. 6 Faculty of Medicine, Ibn Sina college, Jeddah, KSA.


Abstract

Background: Diabetes is a highly prevalent disease, with its complications strongly correlating to the glycemic control of patients.  Objectives: We aimed to review the literature for recent advances in the prognosis and management of diabetic foot ulceration. Methodology: PubMed database was used for articles selection. Papers were obtained and reviewed. PubMed database was used for articles selection, and the following keys terms were used: diabetic foot ulcer, prognosis, and management. Conclusion: Not all managed cases were cured, and some develop resistance to traditional methods and would require unconventional therapies. Nevertheless, this should not deter the physician from offering treatment as this improves prognosis.

Keywords: Diabetic foot ulcer, prognosis, management  


INTRODUCTION

Diabetes Mellitus is a metabolic disorder [1, 2] characterized by increased blood glucose levels [3, 4]. It is a growing public issue around the world, in which a major complication is foot ulceration or the ‘diabetic foot’. In Saudi Arabia, diabetes is rising at an alarming rate, with the country ranking seventh globally in the prevalence of diabetes [5]. Unfortunately, diabetes is not well controlled in many patients in Saudi Arabia [6, 7]. Many patients have reported subpar foot care, and therefore diabetic foot awareness and education are required for many patients [8, 9]. The prevalence of diabetic foot in Saudi Arabia is reported between (26-62%) [10, 11]. The global prevalence is similar (6%), with males having a prevalence of 4.5% [12].

Diabetic foot is an end-result of neuro-vascular compromise in the presence of injury and uncontrolled blood glucose. In Saudi Arabia, the occurrence of diabetic microvascular complications is not clearly documented [13]. Vascular complications have been reported to have an increased mortality risk in diabetic patients [14]. The estimated 5-year mortality reaches up to 30.5%; cost burdens of diabetic extremity care are as high as cancer [15]. Therefore, in this paper, we aimed to review the proper literature discussing the mechanism of diabetic foot ulceration, the pathophysiology behind it, management options, and prognosis for such cases.

METHODOLOGY

PubMed database was used for articles selection, and the following keys used in the mesh ((“Diabetic Foot"[Mesh]) AND (“Prognosis”[Mesh]) OR (“Management"[Mesh])). In regards to the inclusion criteria, the articles were selected based on the inclusion of one of the following topics; diabetic foot ulcer risk factors and prevention. Exclusion criteria were all other articles that did not have one of these topics as their primary endpoint.

REVIEW

Pathophysiology

Diabetic foot ulceration results from uncontrolled hyperglycemia. It is a co-morbid complication of diabetes mellitus. In diabetic patients, evidence of complications should alert the surgeon to the plethora of potential micro and macrovascular complications. The patient would present with other complications of chronic diabetic status in tandem with ulceration [9]. The problem occurs when there is a loss of sensation due to chronic damage from peripheral neuropathy. Peripheral neuropathy would prevent the patient from sensing harmful pressure at the sole of the foot. Because of its location and loss of sensation, it would not be discovered until late.

Prognosis before Management

The surgeon should be wary of the potential development of infections. Risks of superimposed infection in otherwise non-infected ulcers include underlying neuropathy, foot deformity, and unhealed ulcers within three months of initial presentation [16]. When examining the patient for the first time, certain problems should be sought out. Multiple local and systemic factors that lead to the progression of DFU making the prediction of clinical outcomes a challenging task. A systematic review published in the British Medical Journal of Clinical evidence in 2011 states that for people with healed DFU, the 5-year cumulative rate of ulcer recurrence is 66% and amputation is 12% [17].

Diabetic foot ulcers (DFU) is an important complication of type 2 diabetes mellitus (T2DM); it results in major disability and increases the mortality rate [18]. The long duration of T2DM carries the risk of developing multiple complications, which DFU is one of them. A recent study confirms that a 10 years duration of T2DM was significant for a higher incidence of DFU [19]; not forgetting the course of the T2DM as poor/well-controlled, as outcomes can change [20]. The five years survival rate is estimated to be 24.6% in those with a history of DFU [21]. This shows the importance to identify the leading risk factors. This identification not only can help reduce the occurrence rate, delay the occurrence, or lessens the recurrence rate, but also a determinant of the risk helps in the prediction of the prognosis. According to the EURODIALE study done in 2011 which is the largest scale study done to date focused on ulcer outcomes [22], Ulcer prognosis is dependent on ulcer characteristics, epidemiologic factors, and comorbidities. These factors include adequate perfusion, extension, and depth of wound, superimposed infections, and loss of sensation [23, 24]. One study identified independent risk factors for recurrence including osteomyelitis, uncontrolled diabetes, and plantar site of the ulcer. [25]. Infection halts the healing process, in the context of a diabetic patient with uncontrolled glycaemic status. Other factors may also delay wound healing including hypertension, large ulcer of ≥2cm2, previous amputation, and ulceration on the sole [26].

Management

An evidence-based approach is applied when managing diabetic foot; these include controlling blood glucose level, managing co-morbid conditions, improving blood supply, removing necrotic tissue, and applying appropriate foot care. Ulcers, as previously stated, could be subdivided by characteristics such as depth of the wound, i.e. superficial and deep ulcers. Superficial ulcers undergo debridement of dead tissue until bleeding starts —a sign of healthy tissue. Negative-pressure wound closure is applied to extract any infectious residue. Gangrene may develop in superficial ulcers with underlying critical limb ischemia; this is an indication for urgent therapy. Deep ulceration in a diabetic foot is an end-result of inappropriate treatment of an ulcer or infected gangrenous condition [18]. It is a well-known concept that blood supply is the most important factor in wound healing. Therefore, re-vascularisation is a cornerstone in the management of diabetic foot. Endovascular re-vascularisation, performed by a radiologist and vascular surgeons, is done to reduce the need for amputation [27].

DFU is complicated in nature, requiring strict surgical debridement and therapeutic care. One important aspect here is the wound healing accelerating interventions. Therapeutic footwear is one of the very common techniques. It has been demonstrated that it reduces the risk of recurrence of foot pathologies and ulcerations in all patients with diabetic foot, and especially in those with foot deformities [28]. Another common technique is dressings. Despite having slight evidence to support [28], it is a common practice. Comparative researches have demonstrated no significant differences between dressings in the outcome of DFU [29]. The offloading approach is another treatment technique [30]. It helps reducing pressure over the affected area of the foot. Many techniques can be utilized here, such as surgical shoes, immovable glass splints, or total contact splints [31-33]. The last is the most-backed by strong evidence, but perhaps due to its requirement of full immobilization both at home and work, the first is more common [30]. A more invasive DFU treatment option includes debridement. This can be classically achieved by surgery, but some researches recommend utilizing hydrogels as debridement [33]. Hydrogel has been shown to have higher cure rates of DFU compared to gauze dressings. Autolytic and larval are other available debridement techniques [34, 35].

Other concerns with DFU include infection and neuropathic pain. Antibiotics are recommended in cases of failure to heal or signs of local infection. Generally, the choice of drug depends on culture and sensitivity results [28]. For neuropathic pain, a drug that can be used include antidepressants, anticonvulsants, or opioids combined with gabapentin. However, only duloxetine and gabapentin are approved by the Food and Drug Administration (FDA) [28]. New novel therapies are evolving too as adjuvant treatment. Granulocyte-Colony Stimulating Factor (G-CSF) is one example. G-CSF drugs work by increasing the release of endothelial progenitor cells from bone marrow and improves neutrophil function, which is usually affected in diabetic patients [28]. Negative Pressure Therapy (NPT) is another effective adjuvant treatment, but it is mostly reserved as the last alternative [28, 36].

Prognosis after Management

Good glycemic control is known to favor the prognosis of complications in diabetics [37]. Many patients suffer from ulcer recurrence, while this is multifactorial, it would inevitably increase the wound healing period [38]. This recurrence commonly occurs within three years from the previous ulcer, regardless of the management effectiveness of the primary incident [25, 38]. The current approach of treatment has shifted to the multidisciplinary model. A multi-disciplinary approach has been shown to reduce the rate of major amputations in 94% of the studies, although these were of different protocols and varying rate reductions [39]. Delayed or absent referrals, poor patient compliance, and poor communication between physicians may contribute to halting the healing process [40].

Resistance

In some cases, foot ulceration is resistant to conventional management mentioned above, and therefore surgeons could consider vacuum-wound closure and maggot therapy. Maggot therapy is used for debridement of dead tissue, leaving only healing tissue. Systematic reviews and meta-analyses showed maggots’ ability to stimulate rapid healing, and shortening wound healing duration in chronic ulcers [41].

CONCLUSION

Physicians should monitor patient compliance with treatment and lifestyle changes. ،hey should educate patients on the consequences of poor glycemic control —including diabetic foot ulceration.

REFERENCES

  1. Sheikhi H R, Heydari M A, Soleimani M, Sheikhi A R, Mastaelizadeh H, Naderyanfar F. The effect of family-centered education on self-care rate in patients with type 2 diabetes. J. Adv. Pharm. Edu. Res. 2019; 9(2): 89-93.
  2. Kumar A B, Umashankar M S, Porselvi A. Case Report on Dilated Cardiomyopathy in Type 2 Diabetes Mellitus Patient with Hypothyroidism. J. Adv. Pharm. Edu. Res. 2018; 8(2): 1-4.
  3. Adiga U, Kathyayani P. Association of Insulin Resistance with Liver Biomarkers in Type 2 Diabetes Mellitus. Int. J. Pharm. Phytopharm. Res. 2019; 9(1): 88-91.
  4. AlGhamdi S A. Potential Antidiabetic and Antioxidant Effects of Coconut Oil on Streptozotocin-Induced Diabetes in Male Sprague-Dawley Rats. Int. J. Pharm. Phytopharm. Res. 2019; 9(5): 68-76.
  5. Al Dawish MA, Robert AA, Braham R, Al Hayek AA, Al Saeed A, Ahmed RA, Sulaiman Al Sabaan F. Diabetes Mellitus in Saudi Arabia: A Review of the Recent Literature. Current diabetes reviews. 2016;12(4):359-68.
  6. Al-Rowais NA. Glycemic control in diabetic patients in King Khalid University Hospital (KKUH) - Riyadh - Saudi Arabia. Saudi Pharm J. 2014;22(3):203-
  7. Alramadan MJ, Magliano DJ, Almigbal TH, Batais MA, Afroz A, Alramadhan HJ, Mahfoud WF, Alragas AM, Billah B. Glycaemic control for people with type 2 diabetes in Saudi Arabia - an urgent need for a review of management plan. BMC Endocr Disord. 2018;18(1):62.
  8. Al Odhayani AA, Al Sayed Tayel S, Al-Madi F. Foot care practices of diabetic patients in Saudi Arabia. Saudi journal of biological sciences. 2017;24(7):1667-71.
  9. Abdulghani HM, AlRajeh AS, AlSalman BH, AlTurki LS, AlNajashi NS, Irshad M, Alharbi KH, AlBalawi YE, AlSuliman YA, Ahmad T. Prevalence of diabetic comorbidities and knowledge and practices of foot care among diabetic patients: a cross-sectional study. Diabetes, metabolic syndrome and obesity: targets and therapy. 2018;11:417-25.
  10. Al-Hariri MT, Al-Enazi AS, Alshammari DM, Bahamdan AS, Al-Khtani SM, Al-Abdulwahab AA. Descriptive study on the knowledge, attitudes and practices regarding the diabetic foot. Journal of Taibah University medical sciences. 2017;12(6):492-6.
  11. Goweda R, Shatla M, Alzaidi A, Alzaidi A, Aldhawani B, Alharbi H, Sultan N, Alnemari D, Rawa B. Assessment of knowledge and practices of diabetic patients regarding diabetic foot care, in Makkah, Saudi Arabia. Journal of Family Medicine and Health Care. 2017;3(1):17.
  12. Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis (†). Annals of medicine. 2017;49(2):106-16.
  13. Alwin Robert A, Al Dawish MA. Microvascular complications among patients with diabetes: An emerging health problem in Saudi Arabia. Diabetes & vascular disease research. 2019;16(3):227-35.
  14. Sud M, Wang X, Austin PC, Lipscombe LL, Newton GE, Tu JV, Vasan RS, Lee DS. Presentation blood glucose and death, hospitalization, and future diabetes risk in patients with acute heart failure syndromes. European heart journal. 2015;36(15):924-31.
  15. Armstrong DG, Swerdlow MA, Armstrong AA, Conte MS, Padula WV, Bus SA. Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer. Journal of foot and ankle research. 2020;13(1):16.
  16. Jia L, Parker CN, Parker TJ, Kinnear EM, Derhy PH, Alvarado AM, Huygens F, Lazzarini PA, Diabetic Foot Working Group, Queensland Statewide Diabetes Clinical Network (Australia). Incidence and risk factors for developing infection in patients presenting with uninfected diabetic foot ulcers. PloS one. 2017;12(5):e01779
  17. Hunt D. Diabetes: foot ulcers and amputations. BMJ clinical evidence. 2009;2009.
  18. Setacci C, Benevento D, De Donato G, Viviani E, Bracale UM, Del Guercio L, Palasciano G, Setacci F. Focusing on Diabetic Ulcers. Transl Med UniSa. 2020;21:7-9.
  19. Almobarak AO, Awadalla H, Osman M, Ahmed MH. Prevalence of diabetic foot ulceration and associated risk factors: an old and still major public health problem in Khartoum, Sudan? Ann Transl Med. 2017;5(17):340-.
  20. Cardoso HC, Zara A, Rosa S, Rocha GA, Rocha JVC, de Araujo MCE, Quinzani PD, Barbosa YP, Mrué F. Risk Factors and Diagnosis of Diabetic Foot Ulceration in Users of the Brazilian Public Health System. J Diabetes Res. 2019;2019:5319892.
  21. Jeyaraman K, Berhane T, Hamilton M, Chandra AP, Falhammar H. Mortality in patients with diabetic foot ulcer: a retrospective study of 513 cases from a single Centre in the Northern Territory of Australia. BMC Endocr Disord. 2019;19(1):1-.
  22. Prompers L, Schaper N, Apelqvist J, Edmonds M, Jude E, Mauricio D, Uccioli L, Urbancic V, Bakker K, Holstein P, Jirkovska A. Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study. Diabetologia. 2008;51(5):747-55.
  23. Oyibo SO, Jude EB, Tarawneh I, Nguyen HC, Harkless LB, Boulton AJ. A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems. Diabetes Care. 2001;24(1):84-8.
  24. Schaper NC. Diabetic foot ulcer classification system for research purposes: a progress report on criteria for including patients in research studies. Diabetes/metabolism research and reviews. 2004;20 Suppl 1:S90-5.
  25. Dubský M, Jirkovská A, Bem R, Fejfarová V, Skibová J, Schaper NC, Lipsky BA. Risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis in the Eurodiale subgroup. International wound journal. 2013;10(5):555-61.
  26. Kee KK, Nair HKR, Yuen NP. Risk factor analysis on the healing time and infection rate of diabetic foot ulcers in a referral wound care clinic. Journal of wound care. 2019;28(Sup1):S4-s13.
  27. Bracale UM, Ammollo RP, Hussein EA, Hoballah JJ, Goeau-Brissonniere O, Taurino M, Setacci C, Pecoraro F, Bracale G, Giribono AM, Ferrante L. Managing Peripheral Artery Disease in Diabetic Patients: A Questionnaire Survey from Vascular Centers of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS). Annals of vascular surgery. 2020;64:239-45.
  28. Perez-Panero AJ, Ruiz-Munoz M, Cuesta-Vargas AI, Gonzalez-Sanchez M. Prevention, assessment, diagnosis and management of diabetic foot based on clinical practice guidelines: A systematic review. Medicine (Baltimore). 2019;98(35):e16877.
  29. Wu L, Norman G, Dumville JC, O'Meara S, Bell-Syer SE. Dressings for treating foot ulcers in people with diabetes: an overview of systematic reviews. Cochrane Database Syst Rev. 2015(7):CD010471.
  30. 26.     Penny HL. DFU offloading: we know what works, why don't we do it? J Wound Care. 2019;28(Sup5):S3.
  31. Network SI. Management of diabetes. A national clinical guideline. Edinburgh: Scottish Intercollegiate Guidelines Network. 2010.
  32. Astbury J BC, Barnes S. et al. Type 1 diabetes in adults National clinical guideline for diagnosis and management in primary and secondary care 2004 [Available from: https://www.nice.org.uk/guidance/cg15.
  33. Daza Asurmendi P EAA, Ezkurra Agirre P, et al. Guía de Práctica clínica sobre diabetes tipo 2. Guia Salud. 2008.
  34. Edwards J, Stapley S. Debridement of diabetic foot ulcers. Cochrane Database Syst Rev. 2010(1):CD003556.
  35. Elraiyah T, Domecq JP, Prutsky G, Tsapas A, Nabhan M, Frykberg RG, Hasan R, Firwana B, Prokop LJ, Murad MH. A systematic review and meta-analysis of debridement methods for chronic diabetic foot ulcers. J Vasc Surg. 2016;63(2 Suppl):37S-45S e1-2.
  36. Liu S, He CZ, Cai YT, Xing QP, Guo YZ, Chen ZL, Su JL, Yang LP. Evaluation of negative-pressure wound therapy for patients with diabetic foot ulcers: systematic review and meta-analysis. Ther Clin Risk Manag. 2017;13:533-44.
  37. Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet. 2012;379(9833):2243-51.
  38. Hicks CW, Canner JK, Mathioudakis N, Lippincott C, Sherman RL, Abularrage CJ. Incidence and Risk Factors Associated With Ulcer Recurrence Among Patients With Diabetic Foot Ulcers Treated in a Multidisciplinary Setting. The Journal of surgical research. 2020;246:243-50.
  39. Musuuza J, Sutherland BL, Kurter S, Balasubramanian P, Bartels CM, Brennan MB. A systematic review of multidisciplinary teams to reduce major amputations for patients with diabetic foot ulcers. Journal of vascular surgery. 2019.
  40. Barshes NR, Sigireddi M, Wrobel JS, Mahankali A, Robbins JM, Kougias P, et al. The system of care for the diabetic foot: objectives, outcomes, and opportunities. Diabetic foot & ankle. 2013;4.
  41. Tian X, Liang XM, Song GM, Zhao Y, Yang XL. Maggot debridement therapy for the treatment of diabetic foot ulcers: a meta-analysis. Journal of wound care. 2013;22(9):462-9.