Diabetic Foot Ulcers

                                 Dr. KS Dhillon

Introduction

Foot ulcers are among the most common complications in patients who have diabetes mellitus which is not well controlled. The ulcers are the result of poor glycemic control, underlying neuropathy, peripheral vascular disease, or poor foot care. The ulcers are also one of the common causes of osteomyelitis of the foot and amputation of the lower extremities. These ulcers usually occur in the areas of the foot which encounter repetitive trauma and pressure [1]. Staphylococcus is the most common infective organism. The disease is typically chronic. It is commonly encountered in both the outpatient and inpatient settings. 

Diabetic foot ulcers are responsible for more admissions than any other complication in diabetic patients. Diabetes is the leading cause of non-traumatic amputations in the USA. About 5% of patients with diabetes develop foot ulcers and 1% end up with an amputation.

Patient education about the complication and the need for proper medical care will reduce the risk of complications.

Etiology

The etiology of diabetic foot ulcers is multifactorial. The common underlying causes include poor glycemic control, callosities, ill-fitting footwear, foot deformities, improper foot care, underlying peripheral neuropathy, dry skin, and poor circulation.

Neuropathy which eventually leads to a foot ulcer develops in about 60% of diabetics. The risk of a foot ulcer is higher in individuals with a flat foot because they have disproportionate stress across the foot, leading to tissue inflammation in high-risk areas of the foot.

Epidemiology

Foot ulcers develop in 9.1 million to 26.1 million people with diabetes

worldwide [2]. Fifteen to twenty-five percent of patients with diabetes mellitus will develop a diabetic foot ulcer during their lifetime [3]. The number of newly diagnosed diabetics is increasing yearly, and the incidence of diabetic foot ulcers is bound to increase as well.

Diabetic foot ulcers are most prevalent in patients with diabetes mellitus after the age of 45 years.  

Pathophysiology

The development of a diabetic ulcer usually occurs in 3 stages. The first stage is the development of a callus due to neuropathy. Motor neuropathy produces physical deformity of the foot, and sensory neuropathy causes sensory loss that leads to ongoing trauma. Drying of the skin because of autonomic neuropathy produces drying of the skin which is also another contributing factor. Frequent trauma to the callosity results in subcutaneous hemorrhage and it eventually erodes and becomes an ulcer [2].

Patients with diabetes also develop severe atherosclerosis of the small blood vessels in the legs and feet, leading to vascular compromise. The vascular compromise is another cause of diabetic foot infections. Failure of the blood to reach the wound delays wound healing and it eventually leads to necrosis and gangrene.

History and Physical Examination

Taking a good history is important. The history should include the duration of diabetes, glycemic control, other pre-existing complications of diabetes including sensory neuropathy, history of peripheral vascular disease, callus, previous ulcer, prior treatment, and the outcome. The history should also include information regarding the foot and footwear. 

During the clinical examination, the peripheral pulses of the feet must be felt and anatomical anomalies looked for. Also looked for is the presence of callus and signs of vascular insufficiency. There may be loss of hair, and muscle atrophy. The presence of purulence, scabs, and evidence of neuropathy are looked for.

Features that indicate neuropathy include:

Dysesthesia

Anhydrosis

Paresthesia

Hypo or hyperesthesia

Ulcers are usually seen in the weight-bearing areas of the foot such as the plantar metatarsal head, tips of hammer toes, heel, and other prominent areas. Other physical features include brittle nails, calluses, and fissures.

Evaluation

The most common laboratory investigations done in patients with ulcers include a fasting blood sugar, complete metabolic panel, a complete blood count, glycated hemoglobin levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). 

Recent literature and guidelines suggest that in patients with diabetic foot ulcers, results of specimens for culture taken by swabbing do not correlate well with those obtained by deep tissue sampling. This means that superficial swab specimens may be less reliable for guiding antimicrobial therapy as compared to deep tissue specimens [3].

X-rays are taken to look for underlying osteomyelitis and underlying fractures, the presence of air in the subcutaneous tissue, and the presence of foreign body. An MRI is the preferred test if osteomyelitis is suspected. A bone scan with technetium can also be used to diagnose osteomyelitis. Arterial Doppler with ankle-brachial index (ABI) is useful for diagnosing underlying peripheral vascular disease.

The probe-to-bone test (PTB) is performed by probing the ulcer with a sterile metal probe. It can help with the diagnosis of underlying osteomyelitis. If the probe hits the bone, it is a positive test [4]. Positive probe-to-bone test results are useful especially when conducted on patients with diabetes mellitus [5].

Treatment

Treatment of diabetic foot ulcers should be systematic. There is a need to identify if there is any evidence of ongoing infection. A history of chills and fever, in the presence of pain, warmth, erythema, or induration of the ulcer would indicate the presence of infection. Even in the presence of severe diabetic foot infection, there can be minimal systemic signs of infection [6]. 

A decision has to be made whether the ulcer should be managed in the outpatient setting or inpatient setting. Hospitalization would be needed if parenteral antibiotics are required and there are concerns of noncompliance, inability to care for the wound, and ability to offload pressure [7]. Both categories of patients would require treatment with antibiotics.

Organisms that are commonly seen in diabetic foot ulcers include Staphylococcus aureus (Staph aureus), Streptococcus, Pseudomonas aeruginosa, and rarely E. coli. Diabetes patients have a high carriage rate of Staph aureus in the nose and skin, and this increases the chances of infection of the ulcer [8]. Antibiotics are only used if there is an infection in the ulcer. The dose, duration, and type of antibiotic will depend on the severity of the infection.

Outpatients with diabetic ulcers are usually treated with oral cephalosporins or augmentin. If MRSA is suspected, then the patients are treated with linezolid, clindamycin, or cephalexin plus doxycycline or a trimethoprim sulphamethoxazole combination (bactrim). 

Inpatients are treated with parenteral antibiotics. Drugs used include piperacillin-tazobactam (zosyn), and augmentin. If the patient has penicillin allergy, then carbapenems including ertapenem or meropenem are used. Other combinations include adding metronidazole for anaerobic coverage along with quinolones like ciprofloxacin or levofloxacin, or with cephalosporins such as ceftriaxone, cefepime, or ceftazidime. For MRSA intravenous vancomycin, linezolid, or daptomycin can be used [9].

Besides the use of antibiotics in the treatment of diabetic ulcers any

underlying peripheral vascular disease must be treated to improve the blood flow to the ulcers. Poor blood supply limits the oxygen supply and the delivery of antibiotics to the ulcer. Hence, revascularization improves both and there is a better chance of ulcer healing.

The next step is to perform local debridement or removal of calluses. 

If the patient has Charcots foot, then the initial treatment is immobilization with braces or special shoes. Most patients will require a surgical procedure such as arthrodesis or an osteotomy.

Efforts must be made to prevent new ulcers and worsening of the existing ulcer. This can be achieved by offloading the pressure from the site by using walkers or therapeutic shoes [10]. If the wound fails to heal in 30 days, then hyperbaric oxygen therapy can be used. Hyperbaric oxygen therapy improves wound healing and also reduces the rate of complications [11].

Differential Diagnosis

The differential diagnosis includes:

• Squamous cell carcinoma

• Superficial thrombophlebitis

• Synergistic gangrene

• Blunt bone trauma

• Bone tumour

• Gas gangrene

• Lyme arthritis

• Osteomyelitis

• Sarcoid arthritis

• Sickle cell crisis

Staging

One of the commonly used classification for ulcers is the one by Wagner. The classification grades wounds into six grades based on the depth [12].

Grade/ Features

Grade 1-- Superficial ulcer

Grade 2-- Deep ulcer involving tendon bone or joint

Grade 3-- Deep ulcer with abscess or osteomyelitis

Grade 4 -- Gangrene involving the forefoot

Grade 5 -- Gangrene involving the entire Foot

This classification has been criticized for only incorporating ulcer depth and not incorporating other factors known to influence the outcome. One of the most commonly used classification is The University of Texas Classification, which includes an assessment of the depth, the type of infection, and ischemia based on the eventual outcome of the wound [13].

Prognosis

With early detection and appropriate treatment, the prognosis is good. Delay in treatment can have detrimental effects which can lead to amputation of the foot. Patients with chronic diabetic ulcers have a high risk of rehospitalization and prolonged hospitalization.

Complications

The complications include gangrene of the foot, osteomyelitis, amputation of the limb, permanent deformity, and risk of sepsis.

Postoperative Care

Patients who have an amputation will need comprehensive therapy that includes physical therapy, occupational therapy, and they will also need a prosthesis.

Conclusion

Diabetes has a significant number of life-threatening complications. One of them is a foot ulcer. Many patients with diabetes mellitus with a foot ulcer have peripheral vascular disease and neuropathy. 

Many patients with diabetes mellitus with a foot ulcer end up with amputations. The amputation makes them disabled. The key to preventing foot ulcers is education. The primary care provider should educate the patient on the harms of smoking and the need for better control of blood glucose. Patients with diabetes mellitus also need to be taught about proper shoe wear, podiatric care, and control of hyperlipidemia. There is a need to educate the patient and family on preventative measures to minimize morbidity and improve outcomes. 

The dietitian can educate the patient on a healthy diet. During clinic visits, the feet must be examined for skin integrity, pulses, and sensation. Diabetic patients should be told that anytime they have an open wound, they should seek immediate care and avoid homemade remedies. 

Loss of a limb leads to enormous morbidity. Many patients are not able to afford a prosthesis. Most remain disabled for life and have a poor quality of life.

References

1. Singer AJ, Tassiopoulos A, Kirsner RS. Evaluation and Management of Lower-Extremity Ulcers. N Engl J Med. 2018 Jan 18;378(3): 302-303.

2. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017 Jun 15;376(24):2367-2375.

3. Mutluoglu M, Uzun G, Turhan V, Gorenek L, Ay H, Lipsky BA. How reliable are cultures of specimens from superficial swabs compared with those of deep tissue in patients with diabetic foot ulcers? J Diabetes Complications. 2012 May-Jun;26(3):225-9.

4. Malhotra R, Chan CS, Nather A. Osteomyelitis in the diabetic foot. Diabet Foot Ankle. 2014;5. 

5. Mutluoglu M, Uzun G, Sildiroglu O, Turhan V, Mutlu H, Yildiz S. Performance of the probe-to-bone test in a population suspected of having osteomyelitis of the foot in diabetes. J Am Podiatr Med Assoc. 2012 Sep-Oct;102(5):369-73.

6. Eneroth M, Apelqvist J, Stenström A. Clinical characteristics and outcome in 223 diabetic patients with deep foot infections. Foot Ankle Int. 1997 Nov;18(11):716-22.

7. Lipsky BA, Pecoraro RE, Larson SA, Hanley ME, Ahroni JH. Outpatient management of uncomplicated lower-extremity infections in diabetic patients. Arch Intern Med. 1990 Apr;150(4):790-7. 

8. Breen JD, Karchmer AW. Staphylococcus aureus infections in diabetic patients. Infect Dis Clin North Am. 1995 Mar;9(1):11-24.

9. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS, Senneville E., Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;54(12):e132-73.

10. Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003 May 03;361(9368):1545-51.

11. Hanley ME, Manna B. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 18, 2022. Hyperbaric Treatment Of Diabetic Foot Ulcer.

12. Wagner FW. The dysvascular foot: a system for diagnosis and treatment. Foot Ankle. 1981 Sep;2(2):64-122. 

13. Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care. 1998 May;21(5):855-9.