Tuesday, November 3, 2015

THE DIABETIC FOOT

                                       
   
    An  important  underlying  cause leading to diabetic foot problem is neuropathy. Sensory  neuropathy  leads  to a loss of  protective  sensation. Foot  trauma  is unrecognised and leads to ulceration. The ulceration is often the portal of entry for bacteria, leading to cellulites and/ or abscess formation. Motor neuropathy can lead to asymmetric  muscle atrophy, foot deformity (equines deformity) and altered  biomechanics. This  leads to areas of high pressure during standing or walking and repeated  trauma  that may go unrecognised  because of sensory deficit. Autonomic neuropathy results in loss of sweating and dry skin that leads to cracks and  fissures and a portal of entry for bacteria. Diabetes is also associated with an increased risk of peripheral arterial disease and it can be a major factor in non- healing of foot ulcerations.
 
     Diabetic patients can have significant foot infection, with much less pain and no pronounced systemic inflammatory response. A high index of suspicion is therefore required to diagnose foot infection in patients with diabetes.
                                                   

     The skin of the foot is a highly specialized organ. The plantar skin consists of a complex array of fascia, fibrous septae and tangential shearing forces that occur during walking. The dorsal skin is bound to the underlying extensor retinaculum.  Infection tracks along fascial  planes and tendon sheaths. The location of a diabetic foot wound will usually lead surgeon to the underlying cause. An  ulcer at the posterior border of the heel is usually the result of chronic pressure from prolonged contact with bedding, friction from rubbing against rough bed sheets and lack of elevation. An ulcer about the plantar foot is almost always due to i) excessive pressure and time between the foot and the contact surface, ii) neuropathy and iii) deformity of the foot ( equines contracture). Understanding  the underlying cause will allow an effective wound care. The single best means of reducing pressure on the sole of the foot  is to employ non- weight bearing of the involved  limb through use of crutches or walker. This  may not always be practical but effort should be made to emphasize compliance. Use of standard off- loading shoes are also recommended.
   
    Pain in a neuropathic  foot is usually related to an underlying infection. After a thorough surgical preparation, in the emergency room, to remove debris and allow proper evaluation, the wound is probed to determine its depth and tissues involved. Osteomyelitis should be considered if the wound is deeper than the dermis layer. Most patients with diabetes who present  with a severe foot infection have chronically poor glycemic  control, chronic anaemia, poor nutrition and deficient clinical care. Therefore, laboratory studies and necessary management is essential  before embarking on active treatment.

                                                             

    An important initial  step in treating limb threatening diabetic foot infection is to perform a timely and adequate surgical  debridement. This entails surgical excision of all nonviable and/ or infected  tissue. The plantar spaces are opened by longitudinal incisions with division  of plantar fascia. When pus is present in flexor tendon sheaths, these are opened and drained. In order to appropriately evaluate the viability of the soft tissues and the underlying structures, surgical  debridement should be performed without the use of a tourniquet. If there is exposed bone or suspicion of osteomyelitis, cultures are obtained of this tissue. Wound is irrigated and meticulous hemostasis achieved. Most diabetic foot infections are treated with an empirically selected antibiotic regimen until cultures and sensitivity are available . In a limb threatening infection or osteomyelitis, intravenous therapy should be initiated and followed if possible by oral agents. The use of topical antibiotics has a limited place as may produce the development of resistant strains of colonized surface bacteria.

    A patient with diabetes may not give the typical history of claudication because of associated  neuropathy or lack of activity. It is therefore  important to evaluate the limb for peripheral arterial disease even  in the absence of symptoms. If pedal pulses are not clearly palpable, further vascular studies are indicated. An ankle- brachial index (ABI) should be obtained.

      There is a close association between peripheral arterial disease and coronary disease making then both a high risk for a traditional open bypass procedure. The endovascular options include percutaneous angioplasty  with or without a stent . These procedures cab be performed under local  anaesthesia and sedation and with a high rate of limb salvage .

      The standard treatment of diabetic foot ulcer includes adequate off- loading of weight, frequent ulcer debridement , wound care, treatment of infection and revascularization of ischemic limb. This standard  care in many controlled trials  has resulted in healing of a number of foot ulcers.  However, newer therapeutic  modalities that can improve healing also need to be explored.

     Despite recent advances in surgical and radiologic vascular techniques, a fair number of patients with critical limb ischemia are not eligible for a revascularization procedure.  This is because of anatomic location of the lesion, the extent of the disease or extensive co-morbidity . No  effective pharmacologic  therapy is available  and amputation is often  the only option left.  The cost of managing a patient after amputation has been estimated to be almost  twice that of a successful limb salvage . Therefore, exploring new strategies for ischemic limbs is of major importance.  Bone marrow derived progenitor cells have been identified as a potential new therapeutic target.

    Normal wound healing is a intricate process involving various  cell types, coordinated processes, and complex signaling  interactions.  In a diabetic wound , many of these  responses to inflammatory mediators, matrix production, angiogenesis, and wound contraction have all been  poor and contribute to delayed  healing of a diabetic wound.

     Cell - based therapy is an attractive approach for the treatment of wounds with multiple impairments. Mesenchymal stromal  cells (MSCs) are the multipotent cells derived from stroma  of bone marrow  and other tissues. The local delievery  of  MSC to a diabetic wound might  correct wound healing impairment both indirectly by reversing local  growth - factor deficiency, and directly by improving wound contraction through  interaction with the extracellular  matrix. The decrease in wound size  might  have the potential to offset diabetic - related wound - healing impairment  significantly.
                                                 

       In a  randomized  controlled  trial in 28 diabetic patients with critical limb ischemia, Huang et al reported improvement in limb ischemia and foot ulcers.  By far the most studies of cell therapy have used intramuscular implantation method or intraarterial  injection. Progenitor cell- based  therapy may have great clinical potential.

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