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A. Normal Stages of Wound Healing navigator

  1. Inflammation
  2. Tissue Formation
  3. Tissue Remodelling
  4. Components
    1. Clotting
    2. Inflammation
    3. Granulation tissue formation
    4. Epithelialization
    5. Neovascularization
    6. Collagen Synthesis
    7. Wound contraction
  5. Hair follicle dermal sheaths may play a key role in wound healing [7]

B. Types of Wounds navigator

  1. Acute
    1. Heal rapidly
    2. Orderly restoration of anatomic and functional integrity
  2. Chronic
    1. Do not heal in a timely fashion
    2. Appear to be arrested in inflammatory or proliferative stage
    3. Accumulation of excess extracellular matrix and matrix metalloproteinases
    4. Increased proteinases include collagenase and elastase
    5. These lead to premature degration of collagen and growth factors
  3. Types of Chronic Wounds [2]
    1. Venous Ulcers
    2. Arterial Ulcers
    3. Neuropathic Ulcers
    4. Pressure Ulcers

C. Venous Ulcers [2]navigator

  1. Most commonly in elderly persons [3]
    1. ~1% of persons >60 years
    2. About 500,000 cases per year in USA
    3. Women more than men
  2. Usually due to lower extremity venous stasis associated with venous hypertension:
    1. Congestive Heart Failure
    2. History of deep vein thrombosis or thrombophlebitis
    3. Cirrhosis (obstructed venous return)
    4. Inferior vena cava obstruction (such as thrombosis)
    5. Valvular (venous) incompetence
  3. Symptoms and Signs
    1. Edema
    2. Venous dermatitis
    3. Varicosities (dilated veins)
    4. Lipodermatosclerosis
    5. Ulcer located in gaiter area
    6. Shallow, painful granulation tissue with fibrin
  4. Treatment [2,14]
    1. Leg elevation encouraged
    2. Standard of chronic care is compression therapy at 30-40 mm Hg
    3. High compression more effective than low compression
    4. Debridement of nonviable, necrotic or senescent tissue is standard of care
    5. Surgery for superficial valvular incompetence (endoscopy superior to open methods)
    6. Medical therapy: "rheologic" agents, antibacterials, growth factors
    7. Some topical antimicrobial agents including sulfadiazine or allopurinol powder are beneficial [6]
    8. Tissue-engineered skin (see below): clear efficacy in randomized trials
    9. Growth factors
  5. Types of Compression Devices
    1. Unna boots
    2. Compression stockings / bandage
    3. Elastic wraps
    4. Orthotic compression devices
    5. Pneumatic (air) compression pumps
  6. Limb Compression Bandage [3]
    1. 24 weeks of limb compression bandage can heal many venous ulcers
    2. Wound duration <6 months and wound size <5cm2 suggest that bandages will heal ulcers
    3. Larger and more chronic wounds should be treated more aggressively
  7. Rheologic Agents
    1. May act by reducing blood viscosity, increasing blood flow
    2. Pentoxifylline adjunctive therapy is clearly beneficial [8]
    3. Pentoxifylline dose 1200mg/day required 4-8 patients treated for each 1 benefited
    4. Aspirin 81-325mg po qd benefitical when added to compression approaches
  8. Growth Factors [2]
    1. GM-CSF: perilesional injections have shown benefit; topical being studied
    2. Keratinocyte growth factor 2 (KGF-2): early trials showing efficacy
    3. Calcitonin gene-related peptide (CGRP): healing in early study

D. Arterial Ulcers [2,11] navigator

  1. Usually in patients with peripheral arterial disease (PAD)
    1. Concomitant cardiac or cerebrovascular disease
    2. Claudication typically present
    3. Impotence
    4. Pain in distal foot
    5. Venous disease in ~25% of cases
  2. Risk Factors
    1. Smoking
    2. Diabetes Mellitus (DM) [11]
    3. Hypertension
    4. Lack of exercise
  3. Symptoms and Signs
    1. Abnormal pedal pulses often with cool limbs
    2. Check ankle-brachial index: reduced in PAD
    3. Femoral bruit
    4. Ulcers usually deep, located over bony prominances
    5. Ulcers usually with sharply demarcated borders, yellow base, or necrosis
    6. Exposure of tendons
  4. Ankle-Brachial Index (ABI)
    1. To calculate ABI, use higher of the two arm pressures
    2. For right ABI, use higher of right leg DP or TA with higher of arm pressures
    3. For left ABI, use higher of left leg DP or TA with higher of arm pressures
    4. ABI = highest right or left leg arterial pressure ÷ highest arm pressure
    5. ABI > 1.30 implies noncompressible (vascular calcification) artery
    6. ABI 0.91-1.3 is normal range
    7. ABI 0.41-0.9 is mild to moderate PAD
    8. ABI 0.00-0.40 is severe PAD
  5. Treatment
    1. Control of underlying medical conditions
    2. Exercise, increasing as tolerated
    3. Revascularization as needed
    4. Antiplatelet agents: aspirin and/or clopidogrel
    5. Infections treated with appropriate antibiotics (based on wound tissue culture)

E. Neuropathic Ulcers [2] navigator

  1. Most common cause of foot ulcers
    1. Due to peripheral neuropathy with reduced sensation
    2. Most cases associated with longstanding diabetes mellitus (DM) [10,13,14]
    3. Trauma and prolonged pressure are major direct causes
    4. Most common cause of leg amputation
    5. Very high mortality and ulcer recurrence
  2. Symptoms and Signs
    1. Usually plantar aspect of feet in DM
    2. Neurologic disorders
    3. Hansen Disease
  3. Treatment
    1. Reduce all mechanical stress on the area: "offloading"
    2. Sharp wound debridement
    3. Dressings to maintain moist wound environment
    4. Treatment of infection - broad spectrum agents usually required, including anaerobes
    5. Piperacillin/tazobactam (Zosyn®) and ertapenem (Invanz®) have similar efficacy in diabetic foot infections [12]
    6. Topically applied growth factors (becaplermin)
    7. Vascular reconstruction including tissue-engineered skin
    8. Consideration of amputation
  4. Becaplermin (Regranex®) [9]
    1. Topical gel of 0.01% platelet derived growth factor (PDGF)
    2. increases rate and completeness of healing of diabetic foot ulcers
    3. High doses are required for acceleration of healing
  5. Prevention
    1. Surgical correction of bony deformities
    2. Control of diabetes
    3. Adequate foot care
    4. Daily foot inspection

F. Pressure Ulcers navigator

  1. Localized area of Soft-Tissue Injury
    1. Resulting from compression between a bony prominence and an external surface
    2. Caused by tissue ischemia and necrosis secondary to prolonged pressure
    3. Excessive moisture contributes
  2. Altered Mental Status
    1. Major risk factor for pressure ulcers
    2. ~25% of patients have ulcers when transferred from an acute hospital to a nursing home
    3. Prevalence among nursing home residents is ~15%
  3. Treatment
    1. Optimize nutritional status and overall health
    2. Reduction of pressure on specific tissue sites
    3. Debridement of necrotic tissue and debris
    4. Wound cleansing with saline solutions (avoid antiseptics)
    5. Applications of moist, clean dressings
    6. Management of bacterial colonization and infection with topical agents
    7. Only certain topical agents are recommended including oxyquinolone ointment [6]

G. Vasculitic Ulcers navigator

  1. Inflammatory small and medium vessel disease leading to skin destruction
    1. Systemic Vasculitis - especially ANCA associated diseases
    2. Secondary Vasculitis - rheumatoid arthritis, systemic sclerosis, lupus, others
  2. Often very difficult healing process
  3. Immunosuppression of underlying vasculitis can lead to ulcer healing
  4. Chronic vasculitic ulcers in rhematoid arthritis respond to topical nerve growth factor [4]

H. Wound Dressingsnavigator

  1. Phsyiologically moist wound enviroments are clearly beneficial for:
    1. Acute wounds
    2. Pressure ulcers
  2. No evidence that any specific dressing type enhances healing of other chronic wound types
  3. Moisture retentive dressings are expensive but have benefits:
    1. Reduce infection rates
    2. Debride necrotic tissue
    3. Promote granulation tissue

I. Skin Substitutes (Adapted from Table in Ref [1])navigator

  1. Autologous Split-Thickness Skin Graft
    1. Immediately available; permanent wound coverage
    2. Painful donor; lack of adequate donor site
    3. Used for burns and acute and chronic wounds
  2. Cadaveric Allograft
    1. Immediately available
    2. Graft rejection and possible disease transmission
    3. Used for burns and acute and chronic wounds
  3. Epidermal Grafts
    1. Cultured keratinocyte autografts
    2. Cultured keratinocyte allografts
  4. Cultured Keratinocyte Autografts (Epicel®)
    1. Coverage of large area from small biopsy
    2. Permanent wound coverage with reasonable cosmetic results
    3. Requires 3 weeks for graft cultivation and very expensive
    4. Weak grafts is dermal component not present
    5. For burns and leg ulcers
  5. Cultured Keratinocyte Allografts
    1. No biopsy required; immediately available
    2. Cyropreserved and banking
    3. Expensive with possible disease transmission
    4. Acute and chronic wounds
  6. Dermal Grafts
    1. Cryopreserved allograft skin
    2. Human allograft skin - decellularized (Alloderm®)
    3. Bovine collagen and chondroitin sulfate over Silastic (Integra®)
    4. Fibroblast nylon or bioabsorbable mesh (Dermagraft®)
  7. Cryopreserved Allograft Skin
    1. Immediatelyh available
    2. Good base for cultured keratinocytes when de-epidermized
    3. Temporary coverage and possible disease transmission
    4. For burns
  8. Human Allograft Skin (Alloderm®)
    1. Decellularization, matrix stabillization, freeze drying
    2. Immediately available
    3. Immunologically inert
    4. Allows ultra-thin split-thickness skin graft
    5. Allograft procurement required and possible virus transmission
    6. Mainly used for surgical wound closure
  9. Bovine collagen and chondroitin sulfate over Silastic (Integra®)
    1. Immediately available
    2. Allows ultra-thin split-thickness skin graft; less scarring than other split thickness
    3. Requires complete wound excision before application
    4. Susceptible to infection
    5. Expensive
    6. Used for excised burns
  10. Fibroblast nylon or bioabsorbable mesh (Dermagraft®)
    1. Immediately available
    2. Expensive and requires multiple grafting
    3. Used for burns and diabetic foot ulcers
  11. Composite (Epidermal + Dermal) Skin
    1. Bovine (Apligraf®)
    2. Collagen-glycosaminoglycan substrate with fibroblast + keratinocyte
  12. Bovine Composite Epidermus + Dermus (Apligraf®)
    1. Immediately available and easy handling
    2. Does not require subsequent grafting
    3. Expensive with viability limited to 5 days
    4. Used for venous ulcers
  13. Collagen Substrate with Fibroblasts and Keratinocytes
    1. Immediately available and easy handling
    2. Does not require subsequent grafting
    3. Limited quantity
    4. Used for burns and chronic wounds

References navigator

  1. Bello YM and Phillips TJ. 2000. JAMA. 283(6):716 abstract
  2. De Araujo T, Valencia I, Federman DG, Kirsner RS. 2003. Ann Intern Med. 138(4):326 abstract
  3. Margolis DJ, Berlin JA, Strom BL. 2000. Am J Med. 109(1):15 abstract
  4. Tuveri M, Generini S, Matucci-Cerinic M, Aloe L. 2000. Lancet. 356(9243):1739 abstract
  5. Jull AB, Waters J, Arroll B. 2001. ACP Journal Club. 134(1):14
  6. O'Meara SM, Cullum NA, Majid M, Sheldon TA. 2001. Br J Surg. 88:4 abstract
  7. Jahoda CAB and Reynolds AJ. 2001. Lancet. 358(9291):1445 abstract
  8. Jull A, Waters J, Arroll B. 2002. Lancet. 359(9317):1550 abstract
  9. Becaplermin (PGDF). 1998. Med Let. 40(1031):73 abstract
  10. Jeffcoate WJ and Harding KG. 2003. Lancet. 361(9368):1545 abstract
  11. Boulton AJM, Kirsner RS, Vileikyte L. 2004. NEJM. 351(1):48 abstract
  12. Lipsky BA, Armstrong DG, Citron DM, et al. 2005. Lancet. 366(9498):1695 abstract
  13. Cavanagh PR, Lipsky BA, Bradbury AW, Botek G. 2005. Lancet. 366(9498):1725 abstract
  14. Falanga V. 2005. Lancet. 366(9498):1736 abstract