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===Medical Therapy===
===Medical Therapy===
Appropriate wound care is essential for the management of all diabetic foot ulcers. Uninfected diabetic ulcers do not require antibiotic therapy. For acutely infected wounds, empiric antibiotic with efficacy against [[Gram-positive bacteria|Gram-positive cocci]] should be initiated after obtaining a post-[[debridement]] specimen for [[aerobic]] and [[anaerobic]] culture. Infections with antibiotic-resistant organisms and those that are chronic, previously treated, or severe usually require broader spectrum regimens.
Appropriate [[wound]] care is essential for the management of all [[diabetic foot]] [[ulcers]]. [[infection|Uninfected]] [[diabetic foot|diabetic ulcers]] do not require [[antibiotic]] [[therapy]]. In the contrary for acutely [[infection|infected]] [[wounds]], [[Empiric therapy|empiric]] [[antibiotic]] [[therapy]] with coverage against [[Gram-positive bacteria|Gram-positive cocci]] should be start right after obtaining a post-[[debridement]] specimen for [[aerobic]] and [[anaerobic]] [[Tissue culture|culture]]. [[Infections]] with [[antibiotic]]-resistant [[organisms]] and those that have [[Chronic (medical)|chronic]] or severe [[ulcers]] or have been previously [[treatment|treated]] usually require broader spectrum regimens. [[Treatment]] strategies are dependent on [[ulcer]]'s grade, presence of [[infection]] and [[perfusion]]. For an effective [[treatment]] which lower the chance of the future [[diabetic foot]] [[ulcers]] control of [[blood sugar]], [[pressure]] off-loading and [[treatment]] of other [[Comorbidity|comorbidities]] are also critical. Aim of [[treatment]] should be focused on improving [[prognosis]] and decreasing [[Complication (medicine)|complications]] such as [[amputation]]. In very severe [[ulcers]] or when the [[patient]] has the history of previous [[MRSA]] [[infection]] or colonization within the past year and in regions with high [[prevalence]] of [[MRSA]] [[infection]], [[Methicillin-resistant staphylococcus aureus|MRSA]] should be also covered by [[antibiotic]] [[treatments]]. For an ideal [[treatment]] [[physicians]] should evaluate the severity of [[ulcers]] and possible [[risk factors]] of [[pseudomonas aeruginosa]] or [[Beta-lactamase|extended-spectrum β-lactamase (ESBL)–producing organisms]].


===Surgery===
===Surgery===

Revision as of 20:13, 15 July 2021

Diabetic foot Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Diabetic foot from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]Vishnu Vardhan Serla M.B.B.S. [3]Usama Talib, BSc, MD [4]

Overview

Type 2 diabetes and its complications are now considered as a growing health threat. It is the leading cause of blindness, end stage renal disease, coronary heart disease and foot ulceration which leads to amputations. In general, the incidence of nontraumatic lower extremity amputations has been reported to be at least 15 times greater in those with diabetes than with any other medical illness. Among patients with diabetes, the lifetime risk of having foot ulcer is 15%. Diabetic foot ulcers dramatically worsen the physical, psychological and social quality of life [1]. 1 in every 4 patients with diabetes develops complications. The pathogenesis of diabetics foot is due to two causes i.e. neuropathy and vasculopathy. Due to neuropathy the patient loses sensation whereas, vasculopathy causes poor blood supply to the foot region. Due to both these contributing factors, even a small trauma to the feet can give rise to ulcer or gangrene and may even require amputation. Thus, foot examination by a podiatrist or a doctor is recommended every year.

Historical Perspective

The discovery of the association between diabetes and foot ulceration and subsequent infection dates back to the 1850s. Significant breakthroughs in the management of diabetic foot wounds include the introduction of surgical debridement occurred in the early 1900s by Frederick Treves. He also introduced the critical role of footwear in diabetic foot ulcers. Furthermore the discovery of penicillin in 1928 by Alexander Fleming reduced the mortality rate of diabetic foot patients and their related complications significantly. Throughout the 20th century, advances in surgical limb revascularization and the advent of angioplasty drastically reduced the need for amputation. The latter method remained the mainstays of diabetic foot management, in the 2004 and 2012 Infectious Disease Society of America guidelines.

Classification

Diabetic foot is classified based on ulcer's features in order to assist with clinical decision-making regarding the need for oral or parenteral antibiotics, outpatient management, hospitalization, and surgical intervention. There are multiple methods of classification for diabetic foot. One of them that has been published by The Infectious Disease Society of America (IDSA) in their 2004 guideline and mainly has been focused on the extent of infection and inflammation of the ulcer. In addition another similar classification system has been released by The International Working Group on the Diabetic Foot (IWGDF) in 2012. The aforementioned systems were externally validated in a longitudinal study to assess prognostic value, which demonstrated increased risk for amputation among patients with infections classified as severe. Another widely accepted diabetic foot ulcer classification is Wagner ulcer classification system, which uses some ulcer's features such as depth, in addition to presence of osteomyelitis or gangrene.

Pathophysiology

Diabetic foot is an umbrella term for foot problems in patients with diabetes mellitus. Neuropathy, ischemia and trauma are three main pathogenesis of diabetic foot. Neuropathy is the most common and is responsible in more than 60% of diabetic foot cases. Factors such as high blood glucose, reactive oxygen species, insufficient oxygenation of the nerves and inflammation leads to neuropathy development is diabetic patients and get worse by alcohol use and smoking. Neuropathy can involve motor, autonomic or sensory nerves and is able to involve both large and small fibers. Motor nerve involvement can lead to some mechanical changes in the foot of a diabetic patient, which cause more plantar pressure and higher risk of callus formation. Each and every lead to higher rate of skin breakdown and ulceration. Autonomic neuropathy leads to anhidrosis and impaired function of oil glands, subsequent skin dryness, higher chance of skin breakdown and ulcer formation. Diabetic patients with sensory neuropathy are more prone to ulcer formation and related complications, since they don't feel pain with ever-deepening ulcers. Ischemia is the second best known pathogenesis of diabetic foot could occur due to a higher rate of lower limb atherosclerosis in diabetic patients, compared to normal population. Diabetes related complications such as Micro and macrovascular complications further intensify ischemia. Ischemic changes can be discovered by an impaired ankle brachial index (ABI). Trauma to the foot usually acts as a trigger for diabetic foot. A defective hypoxic response has been explained in diabetic foot, which is related to a transcription factor, named hypoxia‐inducible factor‐1 (HIF‐1). Lower level of HIF‐1 in biopsies of diabetic foot could be related to it's role in wound healing. Some genetic associations (such as MAPK14 gene located on chromosome 6, decreased expression of certain cytokines and growth factors, and the HSPA1B genotype) have been explained in diabetic foot development. Charcot arthropathy, some psychosocial conditions, necrotizing fasciitis (NF), vitamin D deficiency, tinea pedis, onychomycosis and diabetic retinopathy are associated conditions in diabetic foot. On gross pathology, the most common site of ulceration is on the sole of the feet, under the metatarsal head with various depth and possible anatomical deformities of foot. In microscopic evaluations of the ulcers evidences of necrosis, hyperkeratosis, fibrosis, inflammation, cellular debris, granulation tissue and angiogenesis have been found.

Causes

Conditions such as peripheral neuropathy and ischemia are two common causes of diabetic foot ulcer formation. Decreased sensation due to peripheral neuropathy increase the risk of trauma which is another known cause of ulcer formation. Microorganisms such as staphylococcus aureus, pseudomonas aeruginosa, proteus mirabilis, escherichia coli and bacteroides fragilis are responsible for diabetic foot ulcer infection.

Differentiating Diabetes foot other Diseases

Diabetic foot must be differentiated from other diseases that cause foot ulceration, erythema, swelling and skin lesion, such as skin and soft-tissue infections, gas gangrene, cellulitis, deep venous thrombosis and inflammatory disorders.

Epidemiology and Demographics

The incidence of diabetic foot ulcer is approximately 1500 per 100,000 diabetic individuals world wide. Just among the US veterans the incidence of active diabetic foot ulcers is approximately 500 per 100,000 individuals. On the other hand the incidence of active diabetic foot ulcers in United Kingdom has been estimated 220 per 100,000 individuals. Furthermore it's prevalence has been reported 170 per 100,000 individuals among the United Kingdom population. The 5 year risk of mortality in diabetic patients with a foot ulcer is 2.5 times higher than diabetic individuals without a foot ulcer. Based on 2 studies with different follow up duration, mortality rate of diabetic foot has been estimated as 10% and 24% in 16 months and 5 years follow up, respectively. Based on a systematic review and metanalysis done on diabetes patients, diabetic foot was more common among older patients. White people develop diabetic peripheral neuropathy (which is a serious risk factor for diabetic foot) more frequently. In 1987, Borch-Johnsen et al. described a male preponderance for the development of severe microvascular complications and diabetic foot disease is not an exception to this rule. Highest prevelance of diabetic foot has been reported in North America. In contrast Oceania has the lowest prevelance of diabetic foot.

Risk Factors

There are numerous risk factors for diabetic foot development in a diabetic patient, such as poor glycaemic control, inappropriate foot care and footwear, foot deformities, peripheral arterial disease, peripheral neuropathy, history of previous foot ulcer or amputation, infection, high body mass index and poor socioeconomic status. Other comorbidities such as hypertension and dyslipidemia are also responsible as risk factors for diabetic foot ulceration.

Screening

The main focus of diabetic foot screening should be on peripheral neuropathy detection, since foot ulcer development is rare in the absence of neuropathy. In addition to examining the peripheral neuropathy, physicians should search for any evidence of skin integrity loss, anatomical deformities, nail changes and distal pulses when they screen diabetic patients. It is recommended to perform a careful foot examination at least annually in diabetic patients who are over the age of 15. Nevertheless there are some risk stratification systems that can provide a better understanding of how often foot screening should be performed based on each patient. These systems utilize factors such as peripheral arterial disease, impaired protective sensation of foot, anatomical deformities, history of previous foot ulcer or amputation and presence of other concurrent disorders. One of the IWGDF guidelines on the management and prevention of the diabetic foot recommended a foot screening assessment sheet for physical examination in each screening. Physicians should educate patients to perform self foot examination more often. There are diagnostic tools in order to perform a better screening such as Semmes-Weinstein monofilament, tuning fork and biothesiometer.

Natural History, Complications and Prognosis

Diabetic foot is a known complication of diabetes. Diabetic patients who are at risk of foot ulceration, develop diabetic foot which may get infected later. The healing process of diabetic foot usually takes a long time (2-5 months) with proper treatment. The final state of diabetic foot is a necrotic foot. The wound healing process can get prolonged in patients with high elevated body mas-s index or osteomyelitis. Diabetic foot ulcer can cause numerous complications, such as sepsis, osteomyelitis, gangrene, lower limb amputation and death. Chance of amputation is increased with factors such as old age, peripheral vascular disease (PAD), transcutaneous oxygen reduction, poor glycemic control, being on dialysis and osteomyelitis. If left untreated prognosis could be very bad and it eventually can lead to death. Male gender, old age, peripheral vascular disease and concurrent chronic renal failure are related to higher rate of death. The presence of a single ulcer is associated with a particularly good prognosis among patients with diabetic foot, compared to multiple ulcers. Glycemic control improvement, treatment of neuropathy and immediate treatment of ulcers improves the prognosis.

Diagnosis

History and Symptoms

History of previous foot ulceration and poor glycemic control are two common positive history in many patients suffering from diabetic foot. Other possible histories in a diabetic foot patient are nephropathy, retinopathy, neuropathy, previous amputation, trauma and smoking. Diabetic foot patients may present to physicians with numerous symptoms. Nevertheless most common symptoms reported in these patients are burning, pins and needles sensation, discharge and pain. In late stages of ulcer infection fever and rigor are also common.

Physical Examination

Patients with diabetic foot ulcer could appear ill if ulcers are severe or infected. In severe and chronic infected ulcers patients may have fever, tachycardia and low blood pressure. Neuromuscular examination of patients with diabetic foot is usually normal, except in their foot. Altered motor tone, reflexes and sensation is expected in these patients. Neuropathy symptoms score (NSS) and neuropathy disability score (NDS) are helpful in neuropathy assessment of patients with diabetic foot. Findings such as impaired vibration and pressure perception, position sense and thresholds for warm thermal perception favor the diagnosis of sensory neuropathy. It is critical to check the extremities for findings such as ulcers, peeling skin, dilated or varicose veins, shiny skin with reduced hair distribution and broken nail while examining diabetic foot. Moreover infection possibility should be evaluated. Findings such as pus, erythema, Warmth, induration and bad odor suggest the presence of infection. In some cases unroofing a small scar demonstrates a deeper infected abscesses. In the other word, evaluating an ulcer for infection must be done after debridement. Other necessary physical examinations in these patients are checking the capillary filling time, ankle brachial index, tactile and vibration sensation and pressure perception.

Laboratory Findings

Worsened glycemic control could be seen in laboratory evaluation of diabetic foot patients. Even in presence of infection there is no guarantee that measures such as WBC, ESR and CRP be elevated. For detection of main responsible microorganisms biopsy, curettage or aspiration a tissue sample is recommended. It is recommended to obtain a sample from discharge of ulcer's base. Moreover, due to contamination of all ulcers , culture from non-infectious ulcers is not recommended. For confirming osteomyelitis diagnosis and for appropriate antibiotic treatment, it is critical to obtain a bone biopsy. Properly obtained specimens for culture prior to initiating empiric therapy provide useful information for guiding antibiotic selection, particularly in those with chronic or previously treated infections which are commonly caused by gram-negative bacilli or obligate anaerobic organisms.

Electrocardiogram

There are no ECG findings associated with diabetic foot.

X Ray

Although plain X ray is not successful in osteomyelitis diagnosis within the first weeks of involvement, it is recommended to be performed in any diabetic foot patients with a deep or enduring ulcer. X-rays of the diabetic foot can be helpful in detecting foreign bodies, gas, joint effusion and osteolysis.

CT

It is recommended to perform CT scan only if MRI is contraindicated. CT scan is a sensitive modality for detecting abnormal bone appearance in patients with diabetic foot ulceration. Altered appearance of bones such as bone erosions, charcot joint, reduced joint space, osteopenia and osteophyte formation can be detected on CT scan.

MRI

Magnetic resonance imaging (MRI) is specific for osteomyelitis diagnosis. This imaging modality has 90% sensitivity and 85% specificity in diagnosis of diabetic foot ulcers. While MRI is very efficient in diagnosis of diabetic foot, it's usage with contrast materials such as gadolinium is not recommended in diabetic patients with evidences of renal diseases. Magnetic resonance angiography (MRA) can be helpful in evaluation of limb perfusion. Nevertheless it has limited spatial resolution and reports could be influenced by previous stents or implants.

Ultrasound

Colorful doppler ultrasound has 89% and 68% sensitivity for iliac artery and popliteal artery, respectfully. Nevertheless it's sensitivity is higher for anterior and posterior tibial arteries (90%). For a complete evaluation of lower limb perfusion all of the iliac, femoral, popliteal and tibial arteries should be scanned by colorful doppler ultrasound. Doppler ultrasound is not accurate when there is considerable calcification.

Other Imaging Findings

Bone scan and white blood cells scan are two imaging modalities that can be used to assist physicians to better diagnose the diabetic foot ulcerations. Both could be used when there is a high clinical suspicion for osteomyelitis while plain X-rays are negative. Leukocyte or white blood cells scan has a higher specificity for ostemyelitis diagnosis and is accurate even in neuropathic patients, in contrast to the bone scan.

Other Diagnostic Studies

Transcutaneous oxygen pressure (TcPO2) measurement can provide data on how is the perfusion of the involved limb, although it's accuracy is not totally accepted in presence of severe ischemia and edema. Transcutaneous oxygen pressure (TcPO2) measures less than 30 mmHg represent the necessity of a complete treatment, due to very low chance of a spontaneous wound healing. On the other hand measures more than 40 mmHg predict an acceptable chance of a spontaneous wound healing.

Treatment

Medical Therapy

Appropriate wound care is essential for the management of all diabetic foot ulcers. Uninfected diabetic ulcers do not require antibiotic therapy. In the contrary for acutely infected wounds, empiric antibiotic therapy with coverage against Gram-positive cocci should be start right after obtaining a post-debridement specimen for aerobic and anaerobic culture. Infections with antibiotic-resistant organisms and those that have chronic or severe ulcers or have been previously treated usually require broader spectrum regimens. Treatment strategies are dependent on ulcer's grade, presence of infection and perfusion. For an effective treatment which lower the chance of the future diabetic foot ulcers control of blood sugar, pressure off-loading and treatment of other comorbidities are also critical. Aim of treatment should be focused on improving prognosis and decreasing complications such as amputation. In very severe ulcers or when the patient has the history of previous MRSA infection or colonization within the past year and in regions with high prevalence of MRSA infection, MRSA should be also covered by antibiotic treatments. For an ideal treatment physicians should evaluate the severity of ulcers and possible risk factors of pseudomonas aeruginosa or extended-spectrum β-lactamase (ESBL)–producing organisms.

Surgery

Primary Prevention

The primary prevention of diabetic foot ulcer includes control of blood sugar levels , pressure offloading, frequent physical examinations, good foot hygiene, diabetic socks and shoes, and by avoiding injury.

Secondary Prevention

The secondary prevention of diabetic foot ulcer includes pressure offloading, prevention of infection, treatment of infection, debridement and reconstruction of the damaged blood vessels, along with the use of primary preventive strategies.[2]

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

References

  1. Assal JP, Mehnert H, Tritschler HJ, Sidorenko A, Keen H, Hellmut Mehnert Award Workshop Participants (2002). "On your feet! Workshop on the diabetic foot". J Diabetes Complications. 16 (2): 183–94. PMID 12039404.
  2. Armstrong DG, Boulton AJM, Bus SA (2017). "Diabetic Foot Ulcers and Their Recurrence". N Engl J Med. 376 (24): 2367–2375. doi:10.1056/NEJMra1615439. PMID 28614678.


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