Foot ulcer (diabetic)

• Diabetic foot complications are the most common cause for non-traumatic lower limb amputation 1-4
• An estimated 15% of patients with diabetes will develop a foot ulcer during the course of their disease, with 85% of diabetes related lower limb amputations preceded by a foot ulcer 5,6
• Foot disorders are the most common diabetic complication requiring hospitalisation, and are associated with the longest length of stay 6
• Approximately 20% of diabetic inpatients will have foot related complications which require acute care and/or management 1,3
• Osteomyelitis in the diabetic foot generally occurs by the direct extension of infection from underling soft tissue ulcers, with bacteria penetrating cortical bone to access the marrow cavity
• Osteomyelitis is a diagnostic challenge, and imaging is commonly utilised
• The presence of osteomyelitis increases the risk of amputation 1,4,7

Clinical Findings

• The signs and symptoms of infection may be absent or masked by the coexistence of vascular disease or neuropathy 1
• Clinical evaluation should include an assessment of the patient's diabetes
• The physical examination and laboratory findings which have shown to be likelihood of osteomyelitis include
  • Bone exposure – direct visualisation of bone or the ability to probe the base of the wound to bone. Depending on prevalence (sensitivity 38-87%; specificity 85-91%; positive likelihood ratio 6.4; negative LR 0.39) 8-10
  • Ulcer area larger then 2cm2 (sensitivity 56%; specificity 92%) 2
  • Deep (>3mm depth) ulcer (sensitivity 74%, specificity 77%) 2
  • ESR >70mm/h (sensitivity 90%; specificity 100%) 11
  • ALP >135U/L (specificity 100%) 2
  • "Sausage toe" appearance (i.e. red swollen digit) in instances of toe ulceration 12
• Factors that did not modify the probability of osteomyelitis
  • Presence or absence of ulcer inflammation 2
  • Elevated white blood cell count, regardless of cut off applied 13
  • Result of swab culture 14

• Initial procedure for imaging suspected osteomyelitis in the diabetic patient 15
• Evidence of progression or resolution may be used to monitor response to antibiotic treatment
• Characteristic signs of osteomyelitis on plain radiograph include cortical erosion, periosteal reaction, mixed lucency and sclerosis 15
• Pooled sensitivity of 54% and specificity of 68% for osteomyelitis on recent meta-analysis 16
• Sensitivity is limited as radiological changes are delayed for up to four weeks following infection. Typically radiographs don’t show abnormalities until about two weeks after initial infection, when nearly 50% of the bone mineral content has been lost 15,17
• Specificity is limited by difficulty differentiating infection from neuro-osteoarthropathy in a patient with bony destruction (Charcot’s arthropathy) 15
• Plain radiographs can also reveal presence of radio-opaque foreign bodies, gas in soft tissues, calcified arteries fractures or bony abnormalities 3,15
• Normal plain radiographs do not exclude osteomyelitis. An abnormal plain radiographs doubles the odds of osteomyelitis based on a limited systematic review 1

• The gold standard for diagnosis of osteomyelitis15
• Bone biopsy has a role not only in the diagnosis of osteomyelitis, but also the isolation of causative pathogen(s) and their antibiotic sensitivities to guide therapy
• Bone biopsy is performed under sterile conditions either during surgical debridement or percutaneously though uninvolved skin under fluoroscopic or CT guidance 7
• Ideally bone specimens should be sent for both histopathology and microbiology 1,7,22
• Diagnosis of osteomyelitis is based on isolation of bacteria and findings of osteonecrosis and infiltration of the bone with inflammatory cells on histopathology 7
• Superficial swab culture does not reliably predict the bacteria causing osteomyelitis. Swab culture identified the identical pathogen as bone culture in only 22.5% of isolates 23
• Disadvantages of bone biopsy include cost, availability of equipment and expertise, interference by antibiotics in culture results and potential for sampling error (false negative), contamination (false positive), invasiveness of the procedure and patient discomfort
• Bone biopsy should be avoided in patients with advanced vascular disease as the incision for bone biopsy may not heal 1,2
• There have been no published reports of complications associated with bone biopsy of the foot 7

• Preferred advanced imaging modality for diagnosing osteomyelitis 15
• Two metaanalyses reported similar pooled sensitivities of 90% (range 77-100%) and specificities of 79-82.5% (range 40-100%) in the diagnosis of foot osteomyelitis, outperforming plain radiography, ^99mTc bone scanning and leucocyte scintigraphy 16,18
• Advantages
• No ionising radiation
• Optimal visualisation of soft tissue structures, including detection of sinus tracts, deep tissue necrosis, abscesses and other inflammatory changes 15
• High sensitivity in early stages - reveals bony oedema useful for early detection of infection

• Nuclear imaging scans are more sensitive than radiographs for detecting osteomyelitis during early stages of the disease, however they have poor specificity and abnormalities are slow to resolve
• Focal hyperperfusion, hyperaemia and bony uptake on delayed images are signs of osteomyelitis on bone scan. These signs may also be seen in other conditions such as fracture, neuroarthropathy and chronic soft tissue infection 6,19
• Three phase technetium bone scan (Tc-99 MDP) has been reported on recent meta-analyses to be sensitive (80-90% but not specific (28-46%) for osteomyelitis, indicating poor discriminating ability. 16,19 The diagnostic performance was markedly inferior to MRI (diagnostic odds ratio 3.5 versus 150) 18
• Labelled leucocyte scintigraphy with either indium-111 (¹¹¹In) or technetium-99 (^99mTc), improves specificity (to 74 and 85% respectively) for diagnosing acute infections 19
• A combined dual study of Tc-99 MDP and labelled leucocyte scintigraphy (Indium-111) may improve sensitivity and specificity 6,20
• Recent data suggest a role for FDG-PET/CT or SPECT/CT with bone and leukocyte scanning but the utility and cost effectiveness of this approach requires further study and is currently not recommended routinely by expert guidelines 15,21
• Where MRI is unavailable or contraindicated, a radionuclide bone scan and a labelled white blood cell scan is recommended as the best alternative to rule out osteomyelitis15 A negative bone scan effectively excludes osteomyelitis

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Peripheral Arterial Disease (Suspected)